ABSTRACT
Bisphenol S (BPS) is used as an alternative plasticizer to Bisphenol A (BPA), despite limited knowledge of potential adverse effects. BPA exhibits endocrine disrupting effects during development. This article focuses on the impact of bisphenols during oocyte maturation. Connexins (Cx) are gap junctional proteins that may be affected by bisphenols, providing insight into their mechanism during development. Cxs 37 and 43 are crucial in facilitating cell communication between cumulus cells and oocytes. Cumulus-oocyte complexes (COCs), denuded oocytes, and cumulus cells were exposed to 0.05 mg/mL BPA or BPS for 24 h. Both compounds had no effect on Cx43. Cumulus cells exhibited a significant increase in Cx37 expression following BPA (p = 0.001) and BPS (p = 0.017) exposure. COCs treated with BPA had increased Cx37 protein expression, whilst BPS showed no effects, suggesting BPA and BPS act through different mechanisms. Experiments conducted in in vitro cultured cumulus cells, obtained by stripping germinal vesicle oocytes, showed significantly increased expression of Cx37 in BPA, but not the BPS, treated group. BPA significantly increased Cx37 protein expression, while BPS did not. Disrupted Cx37 following BPA exposure provides an indication of possible effects of bisphenols on connexins during the early stages of development.
Subject(s)
Benzhydryl Compounds/pharmacology , Connexin 43/genetics , Connexins/genetics , Phenols/pharmacology , Sulfones/pharmacology , Animals , Benzhydryl Compounds/adverse effects , Cattle , Cumulus Cells/drug effects , Endocrine Disruptors/adverse effects , Endocrine Disruptors/pharmacology , Gene Expression Regulation, Developmental/drug effects , In Vitro Oocyte Maturation Techniques , Oocytes/drug effects , Oocytes/growth & development , Phenols/adverse effects , Plasticizers/adverse effects , Plasticizers/pharmacology , Sulfones/adverse effects , Gap Junction alpha-4 ProteinABSTRACT
Bisphenol A (BPA) and its alternative, bisphenol S (BPS), are widespread endocrine disrupting compounds linked in several studies to poor female fertility. Sufficient oocyte competence and subsequent embryo development are highly dependent on oocyte maturation, an intricate process that is vulnerable to BPA. These effects as well as the effects of its analog, BPS, have not been fully elucidated. Although the harmful consequences of bisphenols on the reproductive system are largely due to interferences with canonical gene expression, more recent evidence implicates noncoding RNAs, including microRNAs (miRNA), as significant contributors. The aim of this work was to test the hypothesis that abnormal expression of key miRNAs during oocyte maturation and embryo development occurs following BPA and BPS exposure during maturation. Using qPCR, primary and mature forms of miR-21, -155, -34c, -29a, -10b, -146a were quantified in an in vitro bovine model of matured cumulus-oocyte complexes, fertilized embryos, and cultured cumulus cells after exposure to BPA or BPS at the LOAEL dose (0.05 mg/mL). Expression of miR-21, miR -155, and miR-29a were markedly increased (P = 0.02, 0.04, <0.0001) while miR-34c and miR-10b were decreased (P = 0.01, 0.01), after BPA treatment. miR-146a expression remained stable. BPS had no effects, suggesting may not exert its actions through these six miRNAs examined. Overall, this study indicates that BPA effects are likely miRNA specific rather than a global effect on miRNA synthesis and processing mechanisms and that its analog, BPS, may not possess the same properties required to interfere with these miRNAs during bovine oocyte maturation.
