Regulation of pig ovarian function

根据加拿大猪肉委员会的数据，到2020年，加拿大境内销售了2800多万头猪，全球出口了500万头猪和500万美元的猪肉产品。由于繁殖效率是猪肉行业盈利能力的关键组成部分，因此更深入地了解猪卵巢功能的调节对于提高猪的繁殖和猪肉行业的成功至关重要。我的研究计划的长期目标是提高我们对猪卵巢生理学的理解，从而制定提高母猪生产力的策略。在卵巢中，雌二醇与促卵泡激素（FSH）协同作用，促进卵泡生成。雌二醇作为一种分泌激素，调节女性生殖功能，如卵母细胞的生长、成熟和子宫的发育。MicroRNAs （miRNAs）是一种小的非编码rna，它们与目标转录物的3‘非翻译区（3’ utr）相互作用以抑制表达。由于每个miRNA能够靶向多个基因，因此它们被认为是多种生理过程的重要调节因子。自噬是清除受损大分子和细胞器的重要细胞过程，在维持细胞稳态中起着至关重要的作用。最近有报道称，自噬参与卵泡发育，并对促性腺激素有反应。在我之前和现在的NSERC发现资助的支持下，我们已经确定miR-378， -21和-574在调节猪颗粒雌二醇产生和卵母细胞成熟中发挥多种作用。我们计划进一步研究自噬在miRNA调节卵巢功能中的作用。考虑到这些mirna的重要性，我们也开始研究它们在卵巢中的表达是如何被调节的。以下是拟议研究的具体目标。1.为了验证miRNA调节的自噬参与颗粒细胞2产生雌二醇的假设。验证卵巢内miRNA-21、-378和-574 mirna的表达受内分泌/旁分泌因子调控的假说3。意义：本研究将进一步揭示miRNA在卵巢功能调节中的作用和机制，并为研究miRNA在卵巢中的表达调控机制提供新的见解。此外，这些实验结果将有助于我们的研究制定高生育潜力后备母猪/母猪的选择策略。因此，该研究项目将继续为我们对猪卵巢生理学的理解做出贡献，并可能在提高猪繁殖效率方面具有潜在的应用前景。这个多学科的研究项目也为下一代科学家提供了一个优秀的、包容性的培训机会。

According to the Canadian Pork Council, over 28 million pigs were marketed within Canada, and 5 million hogs and 5 million dollars of pork products were exported worldwide in 2020. As reproductive efficiency is a key component for profitability in the pork industry, a deeper understanding of the regulation of porcine ovarian function is critical for enhancing pig reproduction and success in the pork industry. The long-term goal of my research program is to improve our understanding of pig ovarian physiology and thereby develop strategies to enhance sow productivity. In the ovary, estradiol acts in concert with follicle stimulating hormone (FSH) to facilitate folliculogenesis. As a secreted hormone, estradiol modulates the of female reproductive function, such as oocyte growth, maturation and the uterus development. MicroRNAs (miRNAs) are small non-coding RNAs that interact with the 3' untranslated region (3'UTR) of their target transcripts to suppress expression. With each miRNA able to target multiple genes, they are known as important regulators of diverse physiological processes. Autophagy is a major cellular process that removes damaged macromolecules, organelles and plays a crucial role in maintaining cell homeostasis. It was recently reported that autophagy involves in follicular development, and is responded to gonadotropin. With the funding support from my previous and current NSERC Discovery grants, we have established that miR-378, -21 and -574 play multiple roles in regulating pig granulosa estradiol production and oocyte maturation. We plan to further study the involvement of autophagy in miRNA regulation of ovarian function. Given the importance of these miRNAs, we also set to investigate how their expression is regulated in the ovary. Below are the specific objectives of the proposed study. 1.To test the hypothesis that miRNA regulated autophagy is involved in estradiol production by granulosa cell 2.To test the hypothesis that the expression of miRNA-21, -378 and -574 miRNAs is regulated by endocrine/paracrine factors in the ovary 3.To test the hypothesis that molecular marker(s) in these important miRNA regions can be identified for selection of potentially high fertility gilts Significance:  The proposed study will further reveal the role and mechanism of miRNAs in ovarian function regulation and offer novel insights on how miRNA expression in the ovary is regulated. Moreover, findings from these experiments will aid our study in developing strategies for selection of gilts/sows with high fertility potential. Thus, this research program will continuously contribute to our understanding of porcine ovarian physiology, which may have potential applications into improving pig reproduction efficiency. . This multidisciplinary research program also offers an outstanding and inclusive training opportunity for the next generation of scientists.