Regulation of pig ovarian function

根据加拿大猪肉理事会的数据，2020年，加拿大国内销售了超过2800万头猪，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，因此深入了解猪卵巢功能的调节对于提高猪的繁殖能力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，促进卵泡发生。雌二醇作为一种分泌性激素，调节女性生殖功能，如卵母细胞的生长、成熟和子宫发育。微小RNA（microRNAs，miRNAs）是一类小的非编码RNA，它与靶基因转录本的3'非翻译区（3' UTR）相互作用，从而抑制其表达。由于每个miRNA都能靶向多个基因，因此它们被认为是多种生理过程的重要调节因子。自噬是一种主要的细胞过程，它清除受损的大分子和细胞器，并在维持细胞内环境稳定方面起着至关重要的作用。近年来研究发现，自噬参与卵泡发育，并对促性腺激素有反应。在我以前和现在的NSERC赠款的资金支持下，我们已经确定miR-378，-21和-574在调节猪颗粒层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调控卵巢功能中的作用。鉴于这些miRNAs的重要性，我们还着手研究它们在卵巢中的表达是如何调节的。以下是拟议研究的具体目标。1.验证miRNA调控的自噬参与颗粒细胞分泌雌二醇的假设2.验证卵巢中miRNA-21、-378和-574的表达受内分泌/旁分泌因子调控的假设3.验证这些重要miRNA区域的分子标记可用于选择潜在高生育力母猪的假设意义：该研究将进一步揭示miRNAs在卵巢功能调控中的作用和机制，并为卵巢中miRNAs的表达调控提供新的见解。此外，这些实验的结果将有助于我们的研究制定选择具有高生育潜力的后备母猪/母猪的策略。因此，这项研究计划将继续有助于我们了解猪卵巢生理，这可能有潜在的应用，以提高猪的繁殖效率。.这个多学科的研究计划还为下一代科学家提供了一个杰出的和包容性的培训机会。

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.