Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1, Canada.
Reproductive Health and Biotechnology Laboratory, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 50 Stone Rd E, Guelph, ON, N1G 2W1, Canada.
Reprod Toxicol. 2021 Jan;99:96-108. doi: 10.1016/j.reprotox.2020.12.001. Epub 2020 Dec 4.
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.
双酚 A（BPA）及其替代品双酚 S（BPS）是广泛存在的内分泌干扰化合物，在几项研究中与女性生育能力低下有关。足够的卵母细胞能力和随后的胚胎发育高度依赖于卵母细胞成熟，这是一个复杂的过程，容易受到 BPA 的影响。这些影响以及其类似物 BPS 的影响尚未完全阐明。尽管双酚类物质对生殖系统的有害后果主要是由于对经典基因表达的干扰，但最近的证据表明非编码 RNA，包括 microRNAs (miRNA)，是重要的贡献者。本工作旨在检验以下假设：即在成熟过程中暴露于 BPA 和 BPS 会导致卵母细胞成熟和胚胎发育过程中关键 miRNA 的异常表达。使用 qPCR，在体外牛成熟卵丘-卵母细胞复合体、受精胚胎和培养的卵丘细胞中定量检测了 miR-21、-155、-34c、-29a、-10b、-146a 的初级和成熟形式，在暴露于 BPA 或 BPS 的 LOAEL 剂量（0.05 mg/mL）后。miR-21、miR-155 和 miR-29a 的表达明显增加（P=0.02、0.04、<0.0001），而 miR-34c 和 miR-10b 的表达则降低（P=0.01、0.01），而 BPA 处理后 miR-146a 的表达保持稳定。BPS 没有影响，这表明它可能不会通过这六种 miRNA 发挥作用。总的来说，这项研究表明，BPA 的作用可能是 miRNA 特异性的，而不是对 miRNA 合成和加工机制的整体影响，其类似物 BPS 可能不具有在牛卵母细胞成熟过程中干扰这些 miRNA 的相同特性。
