报告题目：牛早期妊娠的建立（Establishment of early pregnancy in cattle）
Meeting ID: 953 4015 3801 Passcode: Aloha
报告人简介：Birendra Mishra博士，助理教授，研究兴趣包括营养和环境压力对生殖健康的影响（家禽和牛）、空间辐射对生殖健康的影响以及家禽卵细胞形成的遗传和激素调控，现任夏威夷大学马诺阿分校热爱农林与人力资源学院人类营养、食品与动物科学系助理教授，《PLOS ONE》学术编辑，《Animals》客座编辑。2011年博士毕业于日本岐阜大学，2011-2014年在美国肯塔基大学从事生殖内分泌领域的博士后研究工作，2014-2016年在美国加州大学欧文分校从事生殖毒理领域的博士后研究工作。2016年至今任夏威夷大学马诺阿分校助理教授。截至目前，Birendra Mishra博士以第一或通讯作者在Nature Reviews Endocrinology、Human Reproduction、Molecular Endocrinology、Biology of Reproduction、Reproduction、Molecular and Cellular Endocrinology、Journal of Animal Science Biotechnology等具有国际影响力的期刊发表研究论文40余篇。
Reproductive efficiency is crucial to the production of food animals and the overall profitability of the farm. The majority of pregnancy losses occur in the first month of pregnancy, especially around Day-19 of gestation, mainly due to the inability of the uterus to support conceptus growth or abnormal development of conceptus. As the uterus provides the biological environment for the embryo’s growth and development, alternation in the uterine structure also increases the propensity for conception failure in cattle. Therefore, we hypothesized that uterine functions are essential for the establishment of pregnancy in cattle. To understand the role of uterine functions in the establishment of pregnancy, grass-fed Angus cows (2-3 years old) were used for sampling. The estrous cycles of cows (n="21)" were synchronized using intramuscular injection of a Prostaglandin F2 alpha (On Day-1 and -11). Fifteen cows were bred after detecting the estrus. Endometrial samples (n="6/group)" were collected at Day 15-17 of gestation (pregnant), or estrous cycle (cyclic) or nonpregnant (absence of conceptus). Further, we also collected uterine samples from fertile and infertile (short uteri) cows (n="6/group)." Total RNAs were isolated and subjected to high-throughput RNA sequencing (n="6/group)." The most highly upregulated genes in the pregnant endometrium (vs. cyclic) were MRS2, CST6, FOS, VLDLR, ISG15, IF16, MX2, C15H11orf34, and EIF3M. The most highly upregulated genes in the pregnant endometrium (vs. nonpregnant) are ISG15, IFI6, PENK, PRSS22, MS4A8, CLDN4, C15H11orf34, MRS2, TINAGL1, and R3HDM1. Gene ontology analysis revealed that the biological process related to type-1 interferon signaling (MX1, MX2, IF16, IRF1, ISG15), immune response (IL23A, RSAD2), and extracellular matrix organization (COL1A1, COL1A2, COL3A1, TIMP2) were significantly enriched in the pregnant endometrium. Ion transporters (SLC34A2, SLC2A1, SLC16A11, SLC16A4, and ATP1B1), platelets-derived factors, telomerase activity (HMBOX1, TERF1) and ATPase activities (P2RX6, DNAJB1) were significantly enriched as molecular functions, and endoplasmic reticulum lumen (WNT5B, IL23A1, PENK, TNC, SPARCL1, B2M) was the most significantly enriched cellular component. Our study also reported a significant decrease in the total uterine layer length, endometrial layer, and uterine gland numbers in the infertile cows with short uterine tract compared to normal uteri. This study identifies the Wnt signaling pathway (WNT7A, WNT11, SOX17, CTNNBIP1, DKK1, FZD1, and SFRP4) among the most enriched downregulated pathways. The Wnt singling pathway plays a crucial role in uterine receptivity, peri-implantation period, uterine gland development, and fertility. This study also identified several processes (Oxidation-reduction and cholesterol biosynthetic processes) and pathways (metabolic pathway and carbon metabolism) essential for uterine physiology and a suitable environment during the peri-implantation period. In conclusion, these results suggest that the presence of an embryo induces the endometrial transcripts related to endometrial remodeling, immune response, nutrients, ion transporters, and relevant signaling pathways. Infertile cows with short uteri had fewer numbers of uterine glands and alternation in Wnt signaling pathways. Therefore, uterine functions are crucial for the establishment of pregnancy in cattle.