Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex. Acuña-Hernández Deyanira Guadalupe,Arreola-Mendoza Laura,Santacruz-Márquez Ramsés,García-Zepeda Sihomara Patricia,Parra-Forero Lyda Yuliana,Olivares-Reyes Jesús Alberto,Hernández-Ochoa Isabel Toxicology and applied pharmacology In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC. 10.1016/j.taap.2018.02.011

Ferric ammonium citrate regulates iron death in mature porcine oocytes and their embryonic development in vitro through the NRF2 signaling pathway. Theriogenology Iron death is a novel type of programmed cell death caused by excessive accumulation of iron-dependent lipid peroxidation products; however, the function of iron death during porcine oocyte maturation and embryo growth is poorly understood. This study was conducted to investigate the mechanism of ferric ammonium citrate (FAC) in regulating iron death in mature oocytes in vitro through the NRF2 signaling pathway, and subsequent embryonic development. The experiment was divided into four groups: 0 (control group), 2, 5, and 10 μM FAC. Western blotting (WB), reactive oxygen species (ROS)assays, mitochondrial membrane potential (MMP) assays, and Quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the maturation of porcine oocytes in vitro, the protein content of nuclear transcription factor E2-related factor 2 (Nrf2), the distribution of mitochondria, the level of oxidative stress, and the development of embryos fertilized in vitro. The results showed that with increasing FAC concentrations, the oocyte maturation rate in vitro, Nrf2 protein content, MMP, and cleavage rates of in vitro fertilized embryos decreased (significantly in the 5 μM group); the oxidative stress level was significantly increased; the transcript levels of Nrf2, GPX4, and FTH1 mRNAs were significantly decreased; the expression of ACSL4 was significantly upregulated (P < 0.05); and the blastocyst rate of embryos fertilized in vitro was reduced (significantly in the 2 μM group). In conclusion, FAC can regulate Nrf2 protein levels in porcine oocytes matured in vitro to induce iron death, affecting the maturation rate of oocytes, distribution of mitochondria, level of oxidative stress, expression of iron-death-related genes, and development of embryos after in vitro fertilization. 10.1016/j.theriogenology.2024.10.033