Regulation of pig ovarian function

根据加拿大猪肉委员会的数据，2020年，超过2800万头猪在加拿大国内销售，500万头猪和500万美元的猪肉产品出口到全球。由于繁殖效率是猪肉行业盈利的关键因素，深入了解猪卵巢功能的调节对于提高猪的繁殖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的了解，从而制定提高母猪生产力的策略。在卵巢中，雌二醇与卵泡刺激素(FSH)协同作用，促进卵泡的形成。雌二醇作为一种分泌型激素，调节着女性的生殖功能，如卵母细胞的生长、成熟和子宫发育。MicroRNAs(MiRNAs)是一种小的非编码RNA，它与目标转录物的3‘非翻译区(3’UTR)相互作用，抑制表达。由于每个miRNA能够靶向多个基因，它们被认为是不同生理过程的重要调节因子。自噬是细胞内清除受损大分子、细胞器的重要过程，在维持细胞内环境平衡中起着至关重要的作用。最近有报道称，自噬参与了卵泡的发育，并对促性腺激素起反应。在我之前和现在NSERC发现基金的资助下，我们已经确定miR-378、-21和-574在调节猪颗粒雌激素的产生和卵母细胞成熟方面发挥着多种作用。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调控自噬参与颗粒细胞产生雌二醇的假说2.检验miRNA-21、-378和-574miRNAs的表达受卵巢内分泌/旁分泌因子调控的假说3.验证在这些重要的miRNA区域可以找到分子标记(S)用于选择潜在高生育力母猪的假说意义：本研究将进一步揭示miRNAs在卵巢功能调节中的作用和机制，并为如何调节卵巢miRNA的表达提供新的见解。此外，这些实验的结果将有助于我们的研究开发选择具有高繁殖力潜力的母猪/母猪的策略。因此，本研究计划将继续有助于我们对猪卵巢生理的了解，这可能在提高猪的繁殖效率方面具有潜在的应用价值。。这一多学科研究计划也为下一代科学家提供了一个杰出和包容的培训机会。

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.