Chronic Ethanol Exposure Induces Deleterious Changes in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.
Stem cell reviews and reports
Chronic alcohol consumption in adults can induce cardiomyopathy, arrhythmias, and heart failure. In newborns, prenatal alcohol exposure can increase the risk of congenital heart diseases. Understanding biological mechanisms involved in the long-term alcohol exposure-induced cardiotoxicity is pivotal to the discovery of therapeutic strategies. In this study, cardiomyocytes derived from human pluripotent stem cells (hiPSC-CMs) were treated with clinically relevant doses of ethanol for various durations up to 5 weeks. The treated cells were characterized for their cellular properties and functions, and global proteomic profiling was conducted to understand the molecular changes associated with long-term ethanol exposure. Increased cell death, oxidative stress, deranged Ca handling, abnormal action potential, altered contractility, and suppressed structure development were observed in ethanol-treated cells. Many dysregulated proteins identified by global proteomic profiling were involved in apoptosis, heart contraction, and extracellular collagen matrix. In addition, several signaling pathways including the Wnt and TGFβ signaling pathways were affected due to long-term ethanol treatment. Therefore, chronic ethanol treatment of hiPSC-CMs induces cardiotoxicity, impairs cardiac functions, and alters protein expression and signaling pathways. This study demonstrates the utility of hiPSC-CMs as a novel model for chronic alcohol exposure study and provides the molecular mechanisms associated with long-term alcohol exposure in human cardiomyocytes.
10.1007/s12015-021-10267-y
Effects of early daily alcohol exposure on placental function and fetal growth in a rhesus macaque model.
American journal of obstetrics and gynecology
BACKGROUND:Prenatal alcohol exposure is the most common cause of birth defects and intellectual disabilities and can increase the risk of stillbirth and negatively impact fetal growth. OBJECTIVE:To determine the effect of early prenatal alcohol exposure on nonhuman primate placental function and fetal growth. We hypothesized that early chronic prenatal alcohol would alter placental perfusion and oxygen availability that adversely affects fetal growth. STUDY DESIGN:Rhesus macaques self-administered 1.5 g/kg/d of ethanol (n=12) or isocaloric maltose-dextrin (n=12) daily before conception through the first 60 days of gestation (term is approximately 168 days). All animals were serially imaged with Doppler ultrasound to measure fetal biometry, uterine artery volume blood flow, and placental volume blood flow. Following Doppler ultrasound, all animals underwent both blood oxygenation level-dependent magnetic resonance imaging to characterize placental blood oxygenation and dynamic contrast-enhanced magnetic resonance imaging to quantify maternal placental perfusion. Animals were delivered by cesarean delivery for placental collection and fetal necropsy at gestational days 85 (n=8), 110 (n=8), or 135 (n=8). Histologic and RNA-sequencing analyses were performed on collected placental tissue. RESULTS:Placental volume blood flow was decreased at all gestational time points in ethanol-exposed vs control animals, but most significantly at gestational day 110 by Doppler ultrasound (P<.05). A significant decrease in total volumetric blood flow occurred in ethanol-exposed vs control animals on dynamic contrast-enhanced magnetic resonance imaging at both gestation days 110 and 135 (P<.05); moreover, a global reduction in T∗, high blood deoxyhemoglobin concentration, occurred throughout gestation (P<.05). Similarly, evidence of placental ischemic injury was notable by histologic analysis, which revealed a significant increase in microscopic infarctions in ethanol-exposed, not control, animals, largely present at middle to late gestation. Fetal biometry and weight were decreased in ethanol-exposed vs control animals, but the decrease was not significant. Analysis with RNA sequencing suggested the involvement of the inflammatory and extracellular matrix response pathways. CONCLUSION:Early chronic prenatal alcohol exposure significantly diminished placental perfusion at mid to late gestation and also significantly decreased the oxygen supply to the fetal vasculature throughout pregnancy, these findings were associated with the presence of microscopic placental infarctions in the nonhuman primate. Although placental adaptations may compensate for early environmental perturbations to fetal growth, placental blood flow and oxygenation were reduced, consistent with the evidence of placental ischemic injury.
10.1016/j.ajog.2021.07.028
Fertility intentions to have a second or third child under China's three-child policy: a national cross-sectional study.
Human reproduction (Oxford, England)
STUDY QUESTION:What proportion of people want to have a second or third child after the enactment of the three-child policy in China? SUMMARY ANSWER:Under the three-child policy, fertility intention to have a second child was ∼60% (56% of women vs 65% of men), and fertility intention to have a third child was 13% (10% of women vs 17% of men) among the Chinese population. WHAT IS KNOWN ALREADY:The Chinese government announced the three-child policy on 31 May 2021, allowing all couples to have up to three children. At present, there is a lack of national surveys on the fertility intentions of women and men to have a second or third child under the three-child policy in China. STUDY DESIGN, SIZE, DURATION:In June 2021, a national cross-sectional survey including 9243 respondents aged 18-49 years was conducted online from 31 provinces in China's mainland using a random sampling method. PARTICIPANTS/MATERIALS, SETTING, METHODS:Data on the intention to have a second or third child were collected by anonymous questionnaire. Descriptive statistics were performed to assess fertility intentions. Multivariate and multinomial logistic regression analyses were used to assess the association between fertility intentions and the investigated factors. MAIN RESULTS AND THE ROLE OF CHANCE:Approximately 60% (5493/9243) of the investigated people (55.6% women vs 64.7% men) intended to have a second child, and 13.0% (1203/9243) of them (10.0% women vs 17.1% men) intended to have a third child under China's three-child policy. For non-child respondents, 46.8% of women and 60.4% of men intended to have a second child. For one-child respondents, 47.8% of women and 53.8% of men intended to have a second child. For two-child respondents, 14.4% of women and 25.9% of men intended to have a third child. The mean desired family size was 1.58 children per woman, which was lower than the 1.76 children per man. Notably, the age-specified fertility intentions of men were always higher than those of women. Women with a college or higher degree (adjusted odds ratio [aOR] 0.60, 95% CI 0.42-0.88) and a high-middle (aOR 0.71, 95% CI 0.53-0.95) or high (aOR 0.64, 95% CI 0.48-0.85) household income, as well as men living in urban areas (aOR 0.71, 95% CI 0.58-0.87) and having a high-middle household income (aOR 0.68, 95% CI 0.52-0.90), were associated with a lower intention to have a third child (all P < 0.05). In contrast, men of public service personnel had a higher intention to have a third child than factory workers (aOR 1.44, 95% CI 1.02-2.04, P < 0.05). Meanwhile, approximately one out of five two-child respondents intended to have a third child, while one out of four two-girl respondents (aOR 2.09, 95% CI 1.44-3.04) were willing to have a third child with a strong preference for boys (12.7% for boys vs 2.7% for girls). Economic and childrearing barriers were the leading barriers to having one more child. LIMITATIONS, REASONS FOR CAUTION:The online survey might limit the representativeness of the present study's sample. A large sample size was enrolled and a random sampling method was used to increase the sample diversity and representativeness. WIDER IMPLICATIONS OF THE FINDINGS:This study will assist in estimating the impact on population demographic of the three-child policy in China. Multiple efforts are needed to create a fertility-friendly environment for couples, thereby increasing fertility intentions to have one more child and increasing fertility rates. STUDY FUNDING/COMPETING INTEREST(S):No funding. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER:N/A.
10.1093/humrep/deac101
Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.
Welsh Michelle,Sharpe Richard M,Moffat Lindsey,Atanassova Nina,Saunders Philippa T K,Kilter Sigrid,Bergh Anders,Smith Lee B
PloS one
Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.
10.1371/journal.pone.0013632
Real-time monitoring of nitric oxide and blood flow during ischemia-reperfusion in the rat testis.
Kono Tomoharu,Saito Motoaki,Kinoshita Yukako,Satoh Itaru,Shinbori Chiko,Satoh Keisuke
Molecular and cellular biochemistry
In the present study, we attempted to clarify the role of nitric oxide (NO) and its release during the ischemia-reperfusion rat testis. Eight-week-old male Sprague-Dawley rats were divided into seven groups: age-matched control rats, ischemia (30 minutes)-reperfusion (30 minutes) rats without NG-nitro-L-arginine methyl ester (L-NAME) and L-arginine (L-Arg) treatment, ischemia (30 minutes)-reperfusion (30 minutes) rats treated with L-NAME (10, 30, and 100 mg/kg), ischemia-reperfusion rats treated with L-Arg (10 and 30 mg/kg). Sixty minutes prior to induction of ischemia, L-NAME or L-Arg was administrated intraperitoneally. Real-time monitoring of blood flow and NO release were measured simultaneously with a laser Doppler flowmeter and an NO-selective electrode, respectively. NO2-NO3 and malonaldehyde (MDA) concentrations were measured in the experimental testes. Furthermore, we investigated possible morphological changes in the testis. Clamping of the testicular artery decreased blood flow to 5-20% of the basal level measured before clamping. Immediately following clipping of the artery, NO release rapidly increased. After removing the clip, NO release gradually returned to the basal level. This phenomenon was enhanced by treatment with L-Arg and inhibited by treatment with L-NAME. NO2-NO3 concentrations were increased by treatment with L-Arg and decreased by treatment with L-NAME, while MDA concentrations were increased by treatment with L-NAME and were decreased by treatment with L-Arg. In histological studies, the ischemia-reperfusion caused infiltration of leukocytes and a rupture of microvessels in the testis. Our data suggest that NO has cytoprotective effects on ischemia-reperfusion injury in the rat testis.
10.1007/s11010-005-9105-3
A Systematic Review on the Use of Qualitative and Quantitative Contrast-enhanced Ultrasound in Diagnosing Testicular Abnormalities.
Pinto Sofia P S,Huang Dean Y,Dinesh Ayushi A,Sidhu Paul S,Ahmed Kamran
Urology
Greyscale and color doppler ultrasound are the standard when investigating testicular lesions. However, they cannot provide information on the microvasculature. As such, differentiating benign from malignant tumors is challenging. Contrast-enhanced ultrasound (CEUS) uses ultrasound contrast agents that are exclusively intravascular to image the microvasculature. This review assessed CEUS outcomes in investigating intratesticular lesions and concluded that qualitative CEUS provides the most advantage by confirming vascularity, thus differentiating non-neoplastic from neoplastic lesions with added confidence, allowing for appropriate management. Whilst results for quantitative CEUS are promising in distinguishing malignant from benign neoplasms, further research on its benefits is required.
10.1016/j.urology.2021.02.012
Line and birth season effects on plasma testosterone and oxidative stress parameters in testis of maturing rabbits.
García-Tomás M,Sánchez J,Piles M,Mitjavila M T
Animal reproduction science
Oxidative stress plays a key role in the male reproductive function. Differences between rabbit breeds have been found for testis size, seminiferous tubule diameter, number and size of interstitial and germ cells, etc. Traits related to the redox system could also be affected by genetic factors. It is likely that differences between breeds for these traits would lead to differences in reproductive maturation and fertility. We have investigated in the present paper the age-related changes of the plasma testosterone (TST) concentration, superoxide anion (O(2)(-)) radical formation, superoxide dismutase (SOD) activity, catalase (CAT) activity and thiobarbituric acid-reactive substances (TBARs) level in testis of rabbits in two breeds selected for different aptitudes (Caldes for growth rate and Prat for litter size). The effect of birth season for these traits was also assessed. Major changes in parameters related to oxidative stress were observed at an early age and most probably can be explained by the concomitant changes in testicular structure and function. Both lines showed similar developmental profiles and levels for all the variables studied. There was no interaction between line and birth season, consequently environmental conditions affected both lines in the same manner. Significant differences between males born in different seasons were found for O(2)(-) (4.84+/-0.19RLU/mg tissuemin versus 5.67+/-0.19RLU/mg tissuemin), SOD (6.12+/-0.11U/mg protein versus 7.09+/-0.11U/mg protein) and CAT (0.058+/-0.002K/mg protein versus 0.040+/-0.002K/mg protein). Future studies should take into account differences between seasons for a more precise analysis.
10.1016/j.anireprosci.2009.05.005
Cholesterol-enriched diet disrupts the blood-testis barrier in rabbits.
Morgan Daniel H,Ghribi Othman,Hui Liang,Geiger Jonathan D,Chen Xuesong
American journal of physiology. Endocrinology and metabolism
About 15% of heterosexual couples in the USA suffer from infertility issues; male infertility accounts for ∼50% of all infertility cases and roughly 50% of male infertility is idiopathic. Increased levels of plasma cholesterol affect spermatogenesis and male fertility negatively, but by unclear mechanisms. Clearly, spermatogenesis occurs in immune-privileged seminiferous tubules that are protected by the blood-testis barrier (BTB), and BTB disruption results in sperm damage and male infertility. Accordingly, using rabbits fed a 2% cholesterol-enriched diet for 2, 4, and 6 wk to raise levels of plasma cholesterol, we tested the hypothesis that elevated levels of plasma cholesterol disrupt the BTB functionally and biochemically. The cholesterol-enriched diet increased lipid deposition dramatically and time-dependently in the seminiferous tubules and disrupted the BTB as evidenced by increased IgG staining within the seminiferous tubules. Total protein levels of the tight-junction proteins ZO-1 and occludin were increased in the seminiferous tubules of rabbits fed the cholesterol-enriched diet, and the distribution patterns of tight-junction proteins were markedly affected, including an increased accumulation of tight-junction proteins in endosomes. Disruption of the integrity of the BTB due to increased plasma levels of cholesterol might play a role in male infertility.
10.1152/ajpendo.00416.2014
Quantitative Evaluation of Hepatic Microvascular Perfusion after Ischemia-Reperfusion Injury in Rabbits by Contrast-Enhanced Ultrasound Perfusion Imaging.
Xie Fang,Fei Xiang,Zhang Ming-Bo,Zhang Yan,Wang Hong-Wei,Tang Jie,Tang Wen-Bo,Luo Yu-Kun
Ultrasound in medicine & biology
The aim of this study was to evaluate microvascular perfusion after liver ischemia-reperfusion injury (IRI) in rabbits using the "flash-replenishment" method of contrast-enhanced ultrasound (CEUS) perfusion imaging. Twenty-eight rabbits underwent either 30, 60 or 90 min of ischemia and 120 min of reperfusion. CEUS perfusion imaging was performed using the "flash-replenishment" model, and hepatic microvascular perfusion parameters, including peak intensity (PI), area under the curve (AUC), and hepatic artery-to-vein transit time (HA-HVTT), were calculated. Prolonged ischemia upregulated intracellular adhesion molecule-1 (ICAM-1), alanine transaminase (ALT) and aspartate transaminase (AST) levels. Longer ischemia decreased PI and AUC, but increased HA-HVTT. The perfusion parameters were significantly correlated with Suzuki's pathology scores and ALT and AST levels. The "flash-replenishment" method of CEUS perfusion imaging is an accurate and non-invasive method for evaluating hepatic microvascular perfusion and provides a valuable experimental basis for early prediction of liver IRI damage after liver transplantation or liver resection.
10.1016/j.ultrasmedbio.2018.01.004
Effect of simultaneous coffee/caffeine and ethanol administration on sperm quality and reproductive hormones: an experimental study in Sprague Dawley rats.
Drug and chemical toxicology
Chronic alcohol or coffee/caffeine consumption has been associated with negative effects on male reproductive system. The present study evaluated the possible interaction (combination treatment) of coffee/caffeine and alcohol and its resultant consequence on sperm parameters in rats. Ten groups of adult Sprague Dawley rats ( = 5 per group) were orally gavaged with different quantities of coffee (≈5, 10, and 20 mg/kg caffeine); 30% v/v ethanol (0.5, 1, and 2 g/kg); coffee + ethanol or vehicle (distilled water) daily for 60 days. Sperm parameters, serum sex hormone levels, together with antioxidants and lipid peroxidation status of testis homogenate were evaluated. Single and combined administration of coffee/caffeine and ethanol caused a reduction in sperm count dose-dependently ( 0.0002), but this effect was highest in the combined treatment. Sperm viability, motility, and morphology were unaffected by coffee or ethanol administration, but the combination produced detrimental effects on them. While changes in follicle stimulating hormone were not significant, testosterone and luteinizing hormone levels were decreased significantly and dose-dependently in all experimental groups ( 0.05-0.0001). This effect was most pronounced in the groups that received the combination. Testicular superoxide dismutase and catalase activities, and reduced glutathione and malondiadehye (MDA) levels were not affected by coffee/caffeine, but ethanol decreased ( 0.05) the antioxidants and elevated MDA levels mostly at 2 g/kg. The combination reduced ( 0.0001) the antioxidants and increased MDA levels in testis homogenates at all doses. Combination of coffee/caffeine and ethanol potentiates their detrimental effects on sperm quality and reproductive hormones via reduction in testicular antioxidants activities and elevation of lipid peroxidation in rats.
10.1080/01480545.2020.1802479
Acute alcohol intoxication-induced microvascular leakage.
Doggett Travis M,Breslin Jerome W
Alcoholism, clinical and experimental research
BACKGROUND:Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication increases microvascular permeability and investigated potential signaling mechanisms in endothelial cells that may be involved. METHODS:Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered fluorescein isothiocyanate (FITC)-conjugated albumin (FITC-albumin) from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein kinase (MAPK), myosin light-chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation was assessed by ELISA assays. RESULTS:Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of alcohol dehydrogenase or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAPK, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. CONCLUSIONS:Our results suggest that alcohol intoxication increases microvascular permeability to plasma proteins. The data also suggest the endothelial-specific mechanism involves the p38 MAPK, Rac1, and reorganization of VE-cadherin at junctions. Last, activation of Epac can quickly resolve alcohol-induced endothelial barrier dysfunction.
10.1111/acer.12525
Contrast-enhanced ultrasound imaging for assessing organ perfusion in rainbow trout (Oncorhynchus mykiss).
Goncin Una,Ton Ngoc,Reddy Ashwin,El Kaffas Ahmed,Brinkmann Markus,Machtaler Steven
The Science of the total environment
Contrast-enhanced ultrasound (CEUS) imaging has great potential as a non-lethal, inexpensive monitoring tool in aquatic toxicology. It is a well-established clinical imaging approach that combines real-time, quantitative assessment of organ blood flow, with morphological data. In humans, it has been extensively used to measure changes in blood flow that can be attributed to cancer, inflammation, and other biological abnormalities. However, it has yet to be explored as a tool for fish physiology or environmental toxicology. In this study, our goal was to determine if CEUS could be used to visualize and measure blood flow in the liver of a rainbow trout. All rainbow trout received two injections of an ultrasound contrast agent, microbubbles. A subset received a third injection after administration of propranolol, a non-specific beta1 & 2-blocker, to determine if changes in blood flow could be detected. Ultrasound contrast time-intensity curves (TIC) were obtained, fit to a lognormal model, and different perfusion parameters were calculated. Contrast enhancement was observed in all rainbow trout livers, with high percentage between repeated measurements, including blood flow (80.6 ± 27.3%), area under the curve (73.2 ± 14%), blood volume (84 ± 14.2%) and peak enhancement (86.7 ± 7.5%). After administration of propranolol, we detected a non-significant (p > 0.05) increase in area under the curve (102.6 ± 44.2%), peak enhancement (77.3 ± 106.4), blood volume (48.2 ± 74.5%), and decrease in hepatic blood flow (-17.3 ± 37.1%). These data suggest that CEUS imaging is suitable to measure organ blood flow in fish, and demonstrates tremendous potential for exploring different organs, fish species, and effects of chemical contaminants in future studies.
10.1016/j.scitotenv.2020.141231
Effects of different doses of ethanol on sperm parameters, chromatin structure and apoptosis in adult mice.
Rahimipour Marzieh,Talebi Ali Reza,Anvari Morteza,Sarcheshmeh Abolghasem Abbasi,Omidi Marjan
European journal of obstetrics, gynecology, and reproductive biology
OBJECTIVE:Chronic ethanol abuse causes reproductive organ failure and infertility in both humans and laboratory animals. Since sperm has a critical role in reproductive function, the objective of this unique study was to evaluate the effects of different doses of ethanol on sperm parameters, chromatin structure and apoptosis in adult mice. STUDY DESIGN:A total of 36 adult male mice were equally divided into four groups. Group 1 received ethanol (10%, v/v) containing saccharin (0.2%, w/v), group 2 received ethanol (5%, v/v) containing saccharin (0.1%, w/v), group 3 was treated with saccharin (0.2%, w/v) and group 4 served as control and fed on basal diet for 35 days. Finally, the left cauda epididymis of each animal was cut and placed in Ham's F10 medium. Retrieved spermatozoa were used to analyze count, motility, morphology and viability. Sperm chromatin condensation and DNA integrity were assessed by five different tests including chromomycin A3 (CMA3), toluidine blue (TB), sodium dodecyl sulfate (SDS), and SCD (sperm chromatin dispersion) and sperm apoptosis was assessed by TUNEL. RESULTS:Following ethanol consumption, the sperm count diminished in the ethanol-treated groups. A decrease in sperm motility and an increase in the rate of morphological abnormalities (coiled and broken tails) were seen in the experimental and saccharin groups in comparison with controls. We showed that ethanol consumption can disturb sperm DNA integrity and chromatin remodeling and it may also induce sperm apoptosis. The rates of sperm apoptosis were 51.57 ± 7.45 and 42.85 ± 6.76 in the high ethanol dose and low ethanol dose groups, respectively. CONCLUSION:The results showed that alcohol has negative effects on sperm parameters, chromatin/DNA integrity and apoptosis in mice. These alcohol-induced sperm anomalies may be dose-dependent.
10.1016/j.ejogrb.2013.06.038
Does alcohol have any effect on male reproductive function? A review of literature.
La Vignera Sandro,Condorelli Rosita A,Balercia Giancarlo,Vicari Enzo,Calogero Aldo E
Asian journal of andrology
Although alcohol is widely used, its impact on the male reproductive function is still controversial. Over the years, many studies have investigated the effects of alcohol consumption on sperm parameters and male infertility. This article reviews the main preclinical and clinical evidences. Studies conducted on the experimental animal have shown that a diet enriched with ethanol causes sperm parameter abnormalities, a number of alterations involving the reproductive tract inhibition, and reduced mouse oocyte in vitro fertilization rate. These effects were partly reversible upon discontinuation of alcohol consumption. Most of the studies evaluating the effects of alcohol in men have shown a negative impact on the sperm parameters. This has been reported to be associated with hypotestosteronemia and low-normal or elevated gonadotropin levels suggesting a combined central and testicular detrimental effect of alcohol. Nevertheless, alcohol consumption does not seem to have much effect on fertility either in in vitro fertilization programs or population-based studies. Finally, the genetic background and other concomitant, alcohol consumption-related conditions influence the degree of the testicular damage. In conclusion, alcohol consumption is associated with a deterioration of sperm parameters which may be partially reversible upon alcohol consumption discontinuation.
10.1038/aja.2012.118
Additional deleterious effects of alcohol consumption on sperm parameters and DNA integrity in diabetic mice.
Pourentezari M,Talebi A R,Mangoli E,Anvari M,Rahimipour M
Andrologia
The aim of this study was to survey the impact of alcohol consumption on sperm parameters and DNA integrity in experimentally induced diabetic mice. A total of 32 adult male mice were divided into four groups: mice of group 1 served as control fed on basal diet, group 2 received streptozotocin (STZ) (200 mg kg(-1) , single dose, intraperitoneal) and basal diet, group 3 received alcohol (10 mg kg(-1) , water soluble) and basal diet, and group 4 received STZ and alcohol for 35 days. The cauda epididymidis of each mouse was dissected and placed in 1 ml of pre-warm Ham's F10 culture medium for 30 min. The swim-out spermatozoa were analysed for count, motility, morphology and viability. Sperm chromatin quality was evaluated with aniline blue, toluidine blue, acridine orange and chromomycin A3 staining. The results showed that all sperm parameters had significant differences (P < 0.05), also when sperm chromatin was assessed with cytochemical tests. There were significant differences (P < 0.001) between the groups. According to our results, alcohol and diabetes can cause abnormalities in sperm parameters and chromatin quality. In addition, alcohol consumption in diabetic mice can intensify sperm chromatin/DNA damage.
10.1111/and.12481
Male subfertility effects of sub-chronic ethanol exposure during stress in a rat model.
Alcohol (Fayetteville, N.Y.)
BACKGROUND:Stressful conditions increase alcohol consumption in men. Clinical studies link disruption of the neuroendocrine stress system with alcoholism, but the effect of alcohol in a stress condition on male fertility is still relatively poorly understood. This project was undertaken to evaluate the effect of sub-chronic alcohol in a stress condition on male fertility in a rat model. METHODS:Male Sprague-Dawley rats were randomly divided into a control group, a stress group that was exposed to restraint stress, an ethanol group that was injected with ethanol daily, and a stress + ethanol group that was injected with ethanol daily and was exposed to restraint stress, simultaneously. Furthermore, testis tissue was evaluated histomorphometrically and immunohistochemically for apoptosis using a TUNEL assay after 12 days. Epididymis sperm analysis was done. Blood cortisol and testosterone were measured and expression of hypothalamic kisspeptin (Kiss1), RFRP-3, and MC4R mRNA were evaluated. RESULTS:Ethanol exposure during restraint stress did not alter body weight. Ethanol exposure decreased the cellular diameter and area, and stress increased the cellular diameter and area, in comparison with the control group. In the stress group, in comparison with the other groups, the number of seminiferous tubules decreased and the numerical density of seminiferous tubules increased. In addition, ethanol exposure and/or stress reduced semen analysis parameters (sperm viability and motility), but did not change serum testosterone concentrations. Apoptosis increased in spermatogonia with ethanol exposure, but spermatocytes were not affected. Our data present the novel finding that ethanol and stress reduced hypothalamic Kiss1 mRNA expression, while ethanol exposure decreased hypothalamic RFRP-3 and MC4R mRNA expression. CONCLUSIONS:Ethanol decreased cortisol hormone level during the restraint stress condition and attenuated hypothalamic reproductive-related gene expressions. Therefore, ethanol exposure may induce reduction of sperm viability, increased sperm mortality, and increased apoptosis, with long-term effects, and may induce permanent male subfertility.
10.1016/j.alcohol.2021.08.003
Impact of Alcohol Consumption on Male Fertility Potential: A Narrative Review.
Finelli Renata,Mottola Filomena,Agarwal Ashok
International journal of environmental research and public health
Alcohol abuse disorder is a serious condition, implicating more than 15 million people aged 12 years and older in 2019 in the United States. Ethanol (or ethyl alcohol) is mainly oxidized in the liver, resulting in the synthesis of acetaldehyde and acetate, which are toxic and carcinogenic metabolites, as well as in the generation of a reductive cellular environment. Moreover, ethanol can interact with lipids, generating fatty acid ethyl esters and phosphatidylethanol, which interfere with physiological cellular pathways. This narrative review summarizes the impact of excessive alcohol consumption on male fertility by describing its metabolism and how ethanol consumption may induce cellular damage. Furthermore, the impact of alcohol consumption on hormonal regulation, semen quality, and genetic and epigenetic regulations is discussed based on evidence from animal and human studies, focusing on the consequences on the offspring. Finally, the limitations of the current evidence are discussed. Our review highlights the association between chronic alcohol consumption and poor semen quality, mainly due to the development of oxidative stress, as well as its genotoxic impact on hormonal regulation and DNA integrity, affecting the offspring's health. New landscapes of investigation are proposed for the identification of molecular markers for alcohol-associated infertility, with a focus on advanced OMICS-based approaches applied to the analysis of semen samples.
10.3390/ijerph19010328
Contrast-enhanced ultrasound as a valuable imaging modality for characterizing testicular lesions.
Asian journal of andrology
Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.
10.4103/aja202158
Effects of gradual low-flow reperfusion postconditioning on ischemia-reperfusion injury involving incomplete testicular torsion in rabbits.
Xue Ensheng,Guo Jingjing,Huang Mei,Zhang Yu,Chen Shun,Liang Rongxi
Journal of medical ultrasonics (2001)
PURPOSE:The aim of this study was to investigate the impacts of gradual low-flow reperfusion postconditioning (GLFRP) on testicular ischemia-reperfusion injury (IRI). METHODS:A rabbit testicular ischemia model was established, and rabbits were divided into mild ischemia groups (the IRm, IPm1, IPm2, IPm3, and IPm4 groups) and moderate ischemia groups (the IRM, IPM1, IPM2, IPM3, and IPM4 groups). The IRm and IRM groups underwent direct reperfusion. The IPm1 and IPM1 groups, and the IPm3 and IPM3 groups, received 45 and 30 s maintained low-flow reperfusion. The IPm2 and IPM2 groups, and the IPm4 and IPM4 groups, were subjected to 45 and 30 s gradual low-flow reperfusion. The SOD and Johnsen's score of testicular tissue on the surgical side 3 days after reperfusion were determined. RESULTS:The SOD activities in the IP3 and IP4 groups were higher than those in the IR, IP1, and IP2 groups (P < 0.05), and those in the IP4 group were higher than those in the IP3 group (P < 0.05). The Johnsen's score in the IPm4 group was higher than that in the other groups (P < 0.05), those in the IPM groups were higher than those in the IRM group (P < 0.05), and those in the IPM3 and IPM4 groups were higher than those in the IPM1 and IPM2 groups (P < 0.05). CONCLUSIONS:GLFRP could effectively reduce testicular IRI.
10.1007/s10396-014-0591-3
Physiologic Factors Affecting the Circulatory Persistence of Copolymer Microbubbles and Comparison of Contrast-Enhanced Effects between Copolymer Microbubbles and Sonovue.
Chen Wanping,Cai Hongjiao,Zhang Xiujuan,Huang Danfeng,Yang Jing,Chen Cong,Qian Qingfu,He Yimi,Chen Zhikui
Ultrasound in medicine & biology
Ultrasound contrast agents have been widely used in clinical diagnosis. Knowledge of the physiologic factors affecting circulatory persistence is helpful in preparing long-lasting microbubbles (MBs) for blood perfusion and drug delivery research. In the study described here, we prepared copolymer MBs, compared their characteristics and contrast-enhanced effects with those of SonoVue and investigated the influence of external pressure, temperature, plasma components, renal microcirculation and cardiac motion on their circulatory persistence. The mean size of the copolymer MBs was 3.57 μm, larger than that of SonoVue. The copolymer MBs had longer circulatory persistence than SonoVue. At external pressures of 110 and 150 mm Hg, neither the quantity nor the morphology of the copolymer MBs changed. Further, their quantity and size were similar after incubation at 4°C and 39.4°C and when rabbit plasma and saline were compared. In vivo contrast-enhanced ultrasonography revealed a slightly larger area under the curve for the renal artery than for the renal vein. Thus, copolymer MBs exhibited good stability. However, the quantity of copolymer MBs decreased significantly after 180 s of circulation in an isolated toad heart perfusion model, indicating that cardiac motion was the main factor affecting their circulatory persistence.
10.1016/j.ultrasmedbio.2019.11.019
Association of Alcohol Intake and Semen Parameters in Men With Primary and Secondary Infertility: A Cross-Sectional Study.
Bai Shun,Wan Yangyang,Zong Lu,Li Wei,Xu Xiangdong,Zhao Yun,Hu Xuechun,Zuo Yanzhen,Xu Bo,Tong Xianhong,Guo Tonghang
Frontiers in physiology
Alcohol consumption has commonly been associated with semen parameters. However, the association between alcohol intake and semen parameters in primary and secondary infertile men remains unclear. In this study, 776 infertile men from China were grouped according to alcohol intake: abstainers, moderate drinkers (<9 units/week, up to approximately 100 g of ethanol) and heavy drinkers (≥9 units/week). Semen parameters, including semen volume, sperm concentration, total sperm count, progressive motility and normal morphology were investigated. Alcohol consumption and other lifestyle factors were assessed by questionnaire. Logistic regression models were applied. There was no significant association between alcohol consumption and semen parameters in men with primary infertility. Smaller testis volumes and lower sperm concentrations were found among moderate and heavy drinkers in the secondary infertility group than among abstainers. After adjustment for potential confounders, men with secondary infertility and heavy alcohol consumption had a higher risk of abnormal sperm concentrations (OR = 3.72; 95% CI, 1.04, 13.37). These findings suggest that alcohol intake may decrease sperm concentrations in men with secondary infertility, whereas no association was found in men with primary infertility. It may be beneficial for clinicians to advise male patients with secondary infertility who are seeking fertility treatment to avoid heavy alcohol consumption.
10.3389/fphys.2020.566625
Mast cells and ethanol consumption: interactions in the prostate, epididymis and testis of UChB rats.
Mendes Leonardo O,Amorim João Paulo A,Teixeira Giovana R,Chuffa Luiz Gustavo A,Fioruci Beatriz Aparecida,Pimentel Tatiana Aparecida,de Mello Wilson,Padovani Carlos Roberto,Pereira Sergio,Martinez Marcelo,Pinheiro Patrícia Fernanda F,Oliani Sônia Maria,Martinez Francisco Eduardo
American journal of reproductive immunology (New York, N.Y. : 1989)
PROBLEM:Alcoholism has reached alarming proportions while fertility rates slowing in populations. The assessment of inflammatory effects with emphasis on the variation of the mast cells comparing ethanol chronic ingestion on reproductive organs deserves attention. METHOD OF STUDY:The mast cells were investigated with light microscopy using toluidine blue to locate and count total mast cells and immunohistochemistry to identify the connective tissue mast cells (CTMC). RESULTS:The increase in total mast cells in the prostate, total and degranulated mast cells in epididymis of UChB rats was accompanied by a greater proportion of mucosal mast cells (MMC) in these organs. In addition, a lower incidence of degranulated mast cells was observed in epididymis of control rats. CONCLUSIONS:Ethanol increases the number of total and degranulated mast cells in the prostate and epididymis, as well as associated with increasing MMC, and therefore, it could be leading to inflammation in these organs.
10.1111/j.1600-0897.2010.00958.x
Effect of Rourea coccinea on ethanol-induced male infertility in Wistar albino rats.
Agbodjento Eric,Klotoé Jean Robert,Dougnon Tamègnon Victorien,Sacramento Téniola Isabelle,Dougnon Tossou Jacques,Atègbo Jean-Marc
Andrologia
Ethanol consumption is a risk factor of male infertility. The use of medicinal plants offers an alternative for the treatment of male infertility in developing countries. This study aimed to evaluate the Rourea coccinea effect on ethanol-induced male infertility in Wistar rats. Twenty-five (25) male Wistar rats were randomised into five groups of five rats and treated by oesophageal gavage over a 28-day period. Group 1 (negative control) received distilled water; Group 2 (positive control) received 30% ethanol at 7 mg/kg body weight; Group 3 (reference control) received 30% ethanol co-treated with the reference drug, clomiphene citrate; Groups 4 and 5 (test groups) received 30% ethanol co-treated with Rourea coccinea hydro-ethanolic extract at 200 and 400 mg/kg respectively. Testosterone hormone, sperm parameters and testicular histopathology were evaluated. Ethanol treatment induced a significant reduction (p < .05) in sperm count, motility, viability and a significant increase in sperm abnormalities because of the significant decrease (p < .05) in testosterone levels. These data correlate with the alterations observed in the seminiferous tubule on histopathological examination of the testes. However, co-treatment of ethanol with Rourea coccinea extract or the reference drug restored the ethanol-induced toxic effects on the reproductive organs, sperm profile and testosterone level.
10.1111/and.14047
Antioxidant enzymes activity, lipid peroxidation, oxidative damage in the testis and epididymis, and steroidogenesis in rats after co-exposure to atrazine and ethanol.
Abarikwu S O,Duru Q C,Chinonso O V,Njoku R-C
Andrologia
Concomitant alcohol use and exposure to xenobiotics can adversely affect gonadal functions. This study investigated the oxidative status of the testis and epididymis and steroidogenesis of rats co-exposed to ethanol (EtoH, 5 mg kg(-1) b.wt.) and atrazine (ATZ, 50, 100, 300 mg kg(-1) b.wt.) for 3 weeks. The activities of catalase, superoxide dismutase, glutathione peroxidase, as well as the concentrations of glutathione and malondialdehyde, as indicators of oxidative stress were measured in the homogenates of the testis and epididymis. Testosterone and cholesterol concentrations as well as 17β-hydroxysteroid dehydrogenase (17β-HSD) activity were assayed in the plasma and testis respectively. After the administration of EtoH alone, or in combination with different doses of ATZ, oxidative damage as evident by malondialdehyde level was not observed in both the testis and epididymis. The combine exposure group showed dose-dependent decrease in plasma testosterone and testis cholesterol level and increase in testis 17β-HSD activity compared to the EtoH group. Furthermore, the testes and epididymis of the EtoH-exposed rats treated with high dose of ATZ had severe histopathological damage. Therefore, ATZ-exposed alcohol-treated rats have histological damage of the testis and epididymis and lower testosterone level than EtoH-treated rats.
10.1111/and.12478
Virgin coconut oil extract mitigates testicular-induced toxicity of alcohol use in antiretroviral therapy.
Ogedengbe O O,Naidu E C S,Akang E N,Offor U,Onanuga I O,Peter A I,Jegede A I,Azu O O
Andrology
The consumption of alcohol by people living with HIV/AIDS is associated with a graver prognosis. Long-term use of antiretrovirals may have certain health challenges that may be aggravated by concomitant alcohol use. This study investigated virgin coconut oil (VCO) as an adjuvant to the deleterious effects of highly active antiretroviral therapy (HAART) and alcohol on the cyto-architecture and functioning of the testis. Forty adult male Sprague-Dawley rats, weighing 165~176 g, were divided into eight groups and treated according to protocol. Testicular histology, stereological parameters, seminal fluid, testosterone, luteinizing hormone, follicle-stimulating hormone, the antioxidants marker malondialdehyde (MDA), and antioxidant glutathione (GSH) were examined. The use of ethanol alone and ethanol + HAART showed extensive degeneration in the seminiferous epithelium, decreased semen quality, disorganized basement membrane and widened, hypocellular interstitium. GSH was significantly decreased in the ethanol alone treated group with no significant effect on testosterone, LH, and MDA levels. Adjuvant treatment with VCO at low dose (2.5 mL/kg/bw) improved sperm motility with a partial restoration of the histopathological alterations. High doses of VCO (5.0 mL/kg/bw) showed greater improvement with respect to sperm counts, increased FSH hormonal and GSH antioxidant levels, and a well-preserved testicular cyto-architecture.
10.1111/andr.12490
Effect of ethanol on the changes in testicular protein expression in adult male rats.
Tangsrisakda Nareelak,Iamsaard Sitthichai
Andrologia
Ethanol consumption is a major cause of male infertility, but the exact mechanism is still largely unknown. This study attempted to investigate the effect of ethanol on sperm morphology, acrosome reaction status and the alteration of the testicular protein expressions. Fourteen male rats were divided into control and ethanol groups (n = 7/each group). Ethanol-treated rats received ethanol (5 g/kg, 40% v/v) via oral gavage for consecutive 14 days. Testosterone hormone, sperm parameters, and testicular and epididymal histopathologies were evaluated. In addition, the expressions of testicular proteins including androgen receptor (AR), heat shock protein 70 (HSP70), steroidogenic acute regulatory protein (StAR) and tyrosine-phosphorylated (TyrPho) proteins were investigated. The results showed that ethanol significantly increased percentage of abnormal sperm morphology and acrosome-reacted spermatozoa. Some seminiferous and ductus epididymal histopathologies were observed in ethanol-treated rats. Significantly, ethanol reduced serum testosterone and expressions of testicular AR and TyrPho proteins. However, the overexpression of StAR and HSP70 proteins in ethanol testis was found. It was concluded that the changes in testicular protein expressions may be involved in mechanism of male infertility caused from ethanol consumption.
10.1111/and.13784
Quantitative Evaluation of Renal Cortex Perfusion Using Contrast-Enhanced Ultrasound Imaging Parameters in Ischemia-Reperfusion Injury in Rabbits.
Ultrasound in medicine & biology
The aim of this study was to evaluate blood perfusion of the renal cortex during ischemia-reperfusion (I/R) injury using quantitative contrast-enhanced ultrasound (CEUS) parameters. In this experiment, 24 rabbits were randomly divided into four groups (N = 6): sham-operated group, 24-h post-operation for I/R injury group (24-h I/R), 3-d post-operation for I/R injury group (3-d I/R) and 5 d post-operation for I/R injury group (5 d I/R). All quantitative CEUS parameters were monitored and included the gradient from the start frame to the peak frame (Grad), area under the curve (Area), time-to-peak (TTP), difference between B(intercept intensity at t=0) and A(the intensity attenuation t= 0) and arrival time (AT). Subsequently, we analyzed the changes in these parameters, as well as the correlation between changes in CEUS parameters and pathological parameters. AT and TTP values peaked 3 d after I/R surgery, which correlated with the most significant pathological changes at the same time point. These parameters (such as AT, TTP and Grad) may be useful in dynamically monitoring the severity of tissue damage at the early stage of I/R injury.
10.1016/j.ultrasmedbio.2021.07.013
Protection from ischemia by preconditioning, postconditioning, and combined treatment in rabbit testicular ischemia reperfusion injury.
Zhang Xiaoying,Lv Fangqing,Tang Jie
Archives of biochemistry and biophysics
This study aimed to investigate the protection of ischemic preconditioning (IPreC), ischemic postconditioning (IPostC) and combined treatment on ischemia reperfusion injury (IRI) of testis. A rabbit testicular ischemia reperfusion (IR) model was established with determining of rabbit serum testosterone, nitric oxide (NO), malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), and tissues pathology. After IR, the NO, MDA, PC, SOD, MPO, and GSH-Px expression significantly increased in torsive testis, and significantly decreased after IPreC, IPostC, and combined treatment in torsive testis when compared to contralateral testis. In torsive testis, testicular tissues was severely damaged with spermatogenic cells disappearing, and were filled with light eosin edema liquid. Cell apoptosis index significantly increased, and the ratio of Bcl-2/Bax significantly decreased. After IPreC, IPostC, and combined treatment, testicular tissues were restored to normal, cell apoptosis index significantly decreased, and the ratio of Bcl-2/Bax significantly increased. It indicates that IPreC, IPostC, and combined treatment has an obvious protective effect on testicular IRI, by decreasing the oxidative stress index and cell apoptosis, provides a significant reference for the treatment of testicular torsion induced infertility, and exhibits a great value in clinical applications.
10.1016/j.abb.2016.08.020
Use of contrast enhanced ultrasound in testicular diseases: A comprehensive review.
Tenuta Marta,Sesti Franz,Bonaventura Ilaria,Mazzotta Paola,Pofi Riccardo,Gianfrilli Daniele,Pozza Carlotta
Andrology
BACKGROUND:Contrast-enhanced ultrasound (CEUS) is a sonographic technique that increases the diagnostic accuracy of ultrasound and color Doppler ultrasound (CDUS) when studying testicular abnormalities. However, its role in clinical practice is still debatable because there are no accepted standards regarding how and when this technique should be used for patients with testicular disease. OBJECTIVES:To perform a nonsystematic review of the current literature to highlight the strength and flaws of performing CEUS and to provide a critical overview of current research evidence on this topic. MATERIALS AND METHODS:A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. RESULTS:Strong enhancement of neoplastic lesions (both benign and malignant) during CEUS aids in differential diagnosis with non-neoplastic lesions, which usually appears either nonenhanced or enhanced in a manner similar to that of the surrounding parenchyma. CEUS enhancement has a high predictive value in the identification of neoplastic lesions, whereas a similar or complete absence of enhancement may be interpreted as strong evidence of benignity, although there are exceptions. Literature on quantitative analysis is still scarce, though promising, particularly in distinguishing benign from malignant neoplasms. Furthermore, CEUS may be useful in many emergency situations, such as acute scrotum, blunt scrotal trauma, and focal infarction of the testis. Finally, CEUS can help increase the probability of sperm recovery in azoospermic males. DISCUSSION AND CONCLUSION:CEUS is a safe, easy-to-perform, and cost-effective diagnostic tool that can provide a more accurate diagnosis in testicular lesions and acute scrotal disease. However, further studies with larger cohorts are required to refine the differential diagnosis between benign and malignant neoplasms. Finally, these preliminary results can instigate the development of innovative research on pre-testicular sperm extraction to increase the chances of sperm recovery.
10.1111/andr.13057
Spermatic and testicular damages in rats exposed to ethanol: influence of lipid peroxidation but not testosterone.
Siervo Glaucia E M L,Vieira Henrique R,Ogo Fernanda M,Fernandez Carla D B,Gonçalves Géssica D,Mesquita Suzana F P,Anselmo-Franci Janete Ap,Cecchini Rubens,Guarnier Flavia A,Fernandes Glaura S A
Toxicology
Chronic consumption of ethanol causes morphological and physiological changes in the reproductive system of mammals. Vitamin C has an antioxidant role in organisms by neutralizing the ROS (reactive oxygen species) produced by oxidizing agents and this vitamin has an important function in the male reproductive system. The aim of this study was to evaluate whether vitamin C could prevent or attenuate the alterations in the male reproductive system caused by ethanol consumption. To test this hypothesis, male rats were divided into three experimental groups and treated by gavage for 63 days. The ethanol (E) and ethanol+vitamin C (EC) groups received 2 g/kg of ethanol (25%v/v) daily. In addition to ethanol, the EC group received vitamin C at a dose of 100 mg/day, diluted in water. The control group (C) received only the vehicle. On the 64th experimental day, the animals were anesthetized and euthanized, and blood was collected for plasmatic hormonal analysis. The testis, epididymis, vas deferens, and seminal vesicles were removed and weighed. Sperm from the vas deferens was submitted to morphological and motility analysis. The testis and epididymis were used for oxidative stress and histopathological analysis, sperm count, morphometric analysis of the testis, and stereological analysis of the epididymis. The results showed that vitamin C has a protective effect in the testes of adult male rats, entirely normalizing the parameters of sperm count, spermatogenesis kinetics, lipid peroxidation levels, and sperm motility, as well as partially normalizing the histopathological damage in the testis, epididymis, and sperm morphology. Thus, we concluded that lipid peroxidation is a major mechanism by which ethanol affects the testes and sperm, whereas no plasmatic testosterone alterations were found.
10.1016/j.tox.2015.01.016
Evaluation of lymph node metastasis in a rabbit tumor model: correlations between contrast-enhanced ultrasound and pathologic findings.
Ha Shin-Woo,Lee Hyun-Je,Cho Ae-Sin,Hwang Sung Il,Lee Hak Jong
Ultrasonography (Seoul, Korea)
PURPOSE:The purpose of this study was to evaluate the ability of contrast-enhanced ultrasonography (CEUS) with microbubbles to detect metastatic lymph nodes (LNs) for treatment planning and prognosis. METHODS:For the metastatic LN model, ground VX2 tumor tissues were injected subcutaneously in 12 rabbits, just below the right hind limb. The rabbits were classified into three groups based on the LN area: group A (n=4, >1.9 cm2 ), group B (n=4, 1-1.9 cm2 ), and group C (n=4, <1 cm2 ). The LNs were monitored on CEUS for 10 seconds after injecting 2.5 mL of microbubbles. The percent area of metastatic LNs was calculated on pathologic images and compared with CEUS images. RESULTS:In group A, the mean percent area of metastasis was 40.7%±19.4%. In all cases of metastasis, round-shaped perfusion defects were clearly observed in CEUS images. The metastatic areas were strongly correlated with pathologic findings. The mean percent area in group B was 21.5%±14.4%. The CEUS findings showed multiple nodular perfusion defects, clearly revealing the metastatic areas. In group B, the CEUS and pathologic findings were concordant for three of the four cases. The mean percent area in group C was 9.1%±6.4%. However, in this group, CEUS only detected a small perfusion defect in one case. CONCLUSION:CEUS has the potential to depict characteristic imaging features of metastatic LNs but still has limitations in early detection.
10.14366/usg.19010
Effectiveness of contrast-enhanced ultrasound and serum liver enzyme measurement in detection and classification of blunt liver trauma.
Zhao Da-Wei,Tian Meng,Zhang Le-Tian,Li Tao,Bi Jie,He Jia-Ying,Zhang Ying-Ying
The Journal of international medical research
Objective This study was performed to identify the correlation between contrast-enhanced ultrasound (CEUS) and contrast-enhanced multidetector computed tomography (CE-MDCT) as well as the correlation between serum liver enzyme concentrations and CE-MDCT in classification of the severity of blunt hepatic trauma using CE-MDCT as a reference standard. Materials and methods A blunt liver trauma model was created using 20 rabbits, and CE-MDCT, CEUS, and serum liver enzyme assays were performed. A radiologist and an ultrasound physician independently evaluated the degree of liver trauma. The diagnostic performance of CEUS and serum liver enzyme measurements was compared with that of CE-MDCT using Spearman's correlation analysis and Pearson's correlation analysis, respectively. Results Spearman's rank correlation coefficient between the CEUS-based classification and CE-MDCT was 0.888. The aspartate aminotransferase and lactate dehydrogenase concentrations and the aspartate aminotransferase/alanine aminotransferase ratio were positively correlated with the grade of liver injury; Pearson's correlation coefficients were 0.664, 0.704, and 0.503, respectively. The gamma-glutamyltransferase concentration had a significantly negative correlation with the grade of liver injury (r = -0.467). Conclusions CEUS and serum liver enzyme measurement exhibited high consistency with CE-MDCT for both detection and grading of intraparenchymal lesions in blunt liver trauma. These techniques may permit more accurate diagnosis of liver trauma.
10.1177/0300060516678525
Use of contrast-enhanced ultrasound to monitor rabbit renal ischemia-reperfusion injury and correlations between time-intensity curve parameters and renal ICAM-1 expression.
Li Mingxing,Luo Zhijian,Chen Xiaomei,Xuan Jiqing,Ye Fan,Liu Hui,Chen Kewen
Clinical hemorheology and microcirculation
BACKGROUND:Renal ischemia-reperfusion injury (IRI) is common in renal transplantation, shock, and nephrolithotomy. OBJECTIVE:To quantitatively assess rabbit renal IRI with contrast-enhanced ultrasound (CEUS) and investigate associations between renal cortical time-intensity curve (TIC) parameters and intracellular adhesion molecule-1 (ICAM-1) expression. METHODS:Eighteen white rabbits were randomly assigned into control and IRI groups (n = 9 each), and CEUS examination was performed 24 h after modeling. TIC parameters including arrival time (AT), time to peak intensity (TTP), changes in peak intensity, area under the curve (AUC), and slope of the ascending TIC, and correlations between these parameters and ICAM-1 expression were evaluated with linear correlation analyses. RESULTS:AT, TTP, and AUC were significantly increased in the IRI group (P < 0.05), and the slope of the ascending TIC was significantly lower than that in the control group (P < 0.05). ICAM-1 content in the renal cortex was significantly increased in the IRI group (P < 0.05). In addition, the slope of the ascending TIC negatively correlated with renal ICAM-1 expression (r = -0.923, P < 0.01), whereas AT and TTP positively correlated with ICAM-1 expression (r = 0.697 and 0.892, both P < 0.01). CONCLUSIONS:TIC parameters including the slope of the ascending TIC, AT, and TTP closely correlated with ICAM-1 in the renal cortex, and it is considered that the TIC can be used to quantitatively monitoring renal cortex blood perfusion and CEUS can be used to indirectly evaluate the degree of inflammatory reaction associated with renal IRI. CEUS may be a useful non-invasive method to identify inflammation caused by renal IRI-associated diseases.
10.3233/CH-131768