Bisphenol A and S affect early embryonic development in cattle

双酚 A 和 S 影响牛的早期胚胎发育

• 批准号: RGPIN-2019-04034
• 负责人: Favetta, Laura
• 金额: $ 1.68万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746251
• 关键词: Bisphenol; affect; early; embryonic; development

The cattle industry contributes billions of dollars and thousands of jobs annually to the Canadian economy. A key to its success is the efficient production of healthy bovine embryos. Although the advance in reproductive biotechnologies is striking, the overall fertility of cattle is as low as 35% with the majority of embryo loss during the first weeks of development. Understanding factors that affect bovine embryo development offers a model to study mechanistic pathways that can be translated in other mammals, while improving cattle fertility.  My primary research program combines the basic understanding of embryo development to the focus on the effects of environmental stressors, especially Endocrine Disrupting Compounds (EDCs), on early embryonic loss, with the long-term goal of limiting embryo loss during the first week of development, therefore increasing the chances of producing healthy bovine embryos and improving reproductive biotechnologies in farm animals. This project focuses on the effect of specific EDCs, with the short-term goals of investigating the effects and mechanism of action of Bisphenol A (BPA) and Bisphenol S (BPS), on bovine early embryo development. EDCs are environmental stressors with estrogen-like potential that impact fertility, with BPA being one of the highest volume chemicals produced worldwide. We have shown that bovine oocytes exposure to BPA resulted in spindle abnormalities, reduced meiosis progression, decreased blastocyst development, increased apoptosis and changes in genes and proteins. Concerns over BPA effects led to the use of its analog BPS, that however also has negative effects on oocyte maturation. Both BPA and BPS induce spindle abnormalities and chromosome misalignment in bovine at concentrations significantly lower than the ones observed in humans, suggesting the bovine reproductive system is even more susceptible to bisphenols. These data support our rationale that bisphenols, especially BPA, affect cattle reproductive capability. Therefore, we hypothesize that BPA and BPS contribute to the decrease in cattle reproductive efficiency. Objective 1: Investigate BPA and BPS mechanisms of action during oocyte maturation and early embryo development Objective 2: Investigate the role of BPA and BPS in inducing early embryonic arrest. Objective 3: Study the epigenetic changes caused by BPA and BPS during in vitro development. Objective 4: Identify the changes in the metabolomics profile due to BPA and BPS exposure during in vitro development. A better understanding of the link between EDCs exposure and reproductive decline in cattle is of growing scientific and economic importance. Our research program 1) can substantially contribute to assess whether BPS is a valid substitute for BPA and 2) can drive to implement changes in farm animal environment/feeding system to limit the exposure to bisphenols, and EDCs in general, to reduce their potential effects on cattle reproductive capability.

养牛业每年为加拿大经济贡献数十亿美元和数千个工作岗位。其成功的关键是高效生产健康的牛胚胎。虽然生殖生物技术的进步是惊人的，但牛的总体生育率低至35%，大多数胚胎在发育的第一周丢失。了解影响牛胚胎发育的因素提供了一个模型来研究可以在其他哺乳动物中翻译的机制途径，同时提高牛的生育力。我的主要研究计划结合了对胚胎发育的基本理解，重点关注环境应激因素的影响，特别是内分泌干扰化合物（EDCs），对早期胚胎损失，长期目标是限制胚胎在发育的第一周内损失，从而增加生产健康牛胚胎的机会，并改善农场动物的生殖生物技术。该项目的重点是特定内分泌干扰物的影响，短期目标是研究双酚A（BPA）和双酚S（BPS）对牛早期胚胎发育的影响和作用机制。内分泌干扰物是具有雌激素样潜力的环境压力源，影响生育能力，BPA是全球产量最高的化学品之一。我们已经表明，牛卵母细胞暴露于BPA导致纺锤体异常，减数分裂进程减少，囊胚发育减少，细胞凋亡增加，基因和蛋白质的变化。对BPA影响的担忧导致了其类似物BPS的使用，然而这也对卵母细胞成熟有负面影响。BPA和BPS在牛中诱导纺锤体异常和染色体错位，其浓度显著低于在人类中观察到的浓度，这表明牛生殖系统对双酚更敏感。这些数据支持我们的理论基础，双酚，特别是BPA，影响牛的繁殖能力。 因此，我们假设BPA和BPS有助于降低牛的繁殖效率。目标一：探讨BPA和BPS在卵母细胞成熟和早期胚胎发育过程中的作用机制目的2：探讨BPA和BPS在诱导早期胚胎发育阻滞中的作用。 目的3：研究BPA和BPS在体外发育过程中引起的表观遗传学变化。 目的4：确定体外开发过程中BPA和BPS暴露引起的代谢组学特征变化。 更好地了解内分泌干扰物暴露与牛生殖能力下降之间的联系具有越来越重要的科学和经济意义。我们的研究计划1）可以大大有助于评估BPS是否是BPA的有效替代品，2）可以推动实施农场动物环境/饲养系统的改变，以限制双酚和一般的内分泌干扰物的暴露，以减少其对牛繁殖能力的潜在影响。