Disturbed Gastrointestinal Contractility in a Polycystic Ovary Syndrome Rat Model. Wang Kai-Lee,Hsia Shih-Min,Wang Paulus S,Lin Po-Han Digestive diseases and sciences BACKGROUND:Polycystic ovary syndrome (PCOS), a common hormonal disorder in women, affects 4-18% of women of reproductive age worldwide. A higher prevalence of irritable bowel syndrome was found in women with PCOS. However, the effects and mechanism of PCOS on stomach and colon contractility remain unclear. AIMS:This study aims to evaluate the correlation between PCOS and gastrointestinal disorder. METHODS:Four-week-old female rats were subcutaneously implanted with pellets containing 7.5 mg of dihydrotestosterone for 13 weeks to create PCOS rat models. After vaginal smears, the estrus cycle stage was evaluated. Oral glucose tolerance test was performed after 90 days of treatment. All animals were killed at 17 weeks. The rats were fasted overnight and then anesthetized before decapitation, and the stomach fundus and colon were surgically removed and cultured in oxygenated Krebs solution. Acetylcholine and carbachol were used to evaluate the cholinergic system on contractility. RESULTS:The basal and stomach fundus responded with a reduced frequency and contractility in response to acetylcholine in the PCOS group. Moreover, no difference was found in the spontaneous stomach contractility induced by carbachol in both groups. Lower maximal colon muscle contractility was also found in response to acetylcholine stimulation in PCOS rats. Furthermore, lower maximal muscle contractility was found in response to extracellular calcium levels. MLC20 phosphorylation was also reduced in the gastrointestinal tissue in PCOS rats. CONCLUSIONS:PCOS induces gastroparesis and reduces gastrointestinal muscle contractility. This effect is, at least partly, through reducing the responsiveness of acetylcholine and MLC20 phosphorylation. 10.1007/s10620-019-06001-x

Cigarette smoking and nicotine exposure contributes for aberrant insulin signaling and cardiometabolic disorders. Rehman Kanwal,Haider Kamran,Akash Muhammad Sajid Hamid European journal of pharmacology Cigarette smoking- and nicotine-mediated dysregulation in insulin-signaling pathways are becoming leading health issues associated with morbidity and mortality worldwide. Many cardiometabolic disorders particularly insulin resistance, polycystic ovary syndrome (PCOS), central obesity and cardiovascular diseases are initiated from exposure of exogenous substances which augment by disturbances in insulin signaling cascade. Among these exogenous substances, nicotine and cigarette smoking are potential triggers for impairment of insulin-signaling pathways. Further, this aberrant insulin signaling is associated with many metabolic complications, which consequently give rise to initiation as well as progression of these metabolic syndromes. Hence, understanding the underlying molecular mechanisms responsible for cigarette smoking- and nicotine-induced altered insulin signaling pathways and subsequent participation in several health hazards are quite essential for prophylaxis and combating these complications. In this article, we have focused on the role of nicotine and cigarette smoking mediated pathological signaling; for instance, nicotine-mediated inhibition of nuclear factor erythroid 2-related factor 2 and oxidative damage, elevated cortisol that may promote central obesity, association PCOS and oxidative stress via diminished nitric oxide which may lead to endothelial dysfunction and vascular inflammation. Pathological underlying molecular mechanisms involved in mediating these metabolic syndromes via alteration of insulin signaling cascade and possible molecular mechanism responsible for these consequences on nicotine exposure have also been discussed. 10.1016/j.ejphar.2021.174410

Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome. Journal of pediatric endocrinology & metabolism : JPEM OBJECTIVES:Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction, clinical and/or biochemical hyperandrogenism, and polycystic ovaries. Its pathogenesis is still unclear. This study aimed to investigate the relationship between kisspeptin, leptin, neuropeptide Y (NPY), and neurokinin B (NKB) levels for evaluating the pathogenesis of PCOS. METHODS:Levels of these parameters were analyzed in 20 patients with PCOS, and 16 healthy adolescents. RESULTS:Serum NPY levels were significantly higher in the obese and non-obese PCOS group (p<0.01). There was a negative correlation between the kisspeptin and the NKB levels (p<0.01) in the PCOS group but not in the control group. This negative correlation was also found in both PCOS groups (p<0.01). In the obese PCOS group, serum kisspeptin levels were significantly lower than the control and non-obese PCOS groups (p<0.05) although serum leptin and NPY levels were significantly higher in the obese PCOS group (p<0.01). CONCLUSIONS:The high NPY levels in both obese and non-obese patients with PCOS indicate that NPY plays a role in the pathogenesis independently from obesity. Significantly high leptin and low kisspeptin levels in the obese PCOS group suggested that they may be associated with obesity rather than PCOS. 10.1515/jpem-2021-0487

Gut microbiota alterations reveal potential gut-brain axis changes in polycystic ovary syndrome. Journal of endocrinological investigation PURPOSE:Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder companied with neuroendocrine and metabolic disorders. Gut microbiota has been implicated to play a key role in metabolic diseases and the production of neurotransmitters. Previous studies have reported the alterations in the gut microbiota of PCOS patients and animal models, however, most of the articles did not take the effect of age or diet on gut microbiota into account. The aim of this study was to identify the differential gut microbial species in PCOS patients compared with age and BMI-matched healthy control women. METHODS:We performed physical examinations and dietary survey in 20 women with PCOS (lean PCOS, PL, n = 10; overweight PCOS, PO, n = 10) and 20 healthy control women (lean control, CL, n = 10; overweight control, CO, n = 10), and collected the blood on the days 1-3 of the menstrual cycle for the measurement of endocrine and metabolic profiles, and inflammatory factors; and collected the feces in non-menstrual period to investigate the composition of gut microbiota by sequencing the V4 region of the 16S rDNA gene in fecal samples. The correlations between clinical parameters and the differential species were evaluated. RESULTS:Dietary analysis showed that the intake of dietary fiber, vitamin D were significantly decreased in PCOS. For the first time, our study found an increase of gamma-aminobutyric acid (GABA)-producing species in PCOS, including Parabacteroides distasonis, Bacteroides fragilis and Escherichia coli, which significantly positively correlated with serum LH levels and LH:FSH ratios. CONCLUSIONS:GABA-producing bacteria that were increased in PCOS, including Parabacteroides distasonis, Bacteroides fragilis and Escherichia coli, showed positive relationship with serum LH levels and LH:FSH ratios. In conclusion, gut microbial dysbiosis in women with PCOS is associated with neuroendocrine changes, revealing a potential gut-brain axis in PCOS. 10.1007/s40618-020-01481-5