Division of Animal Sciences, University of Missouri, Columbia, MO 65211.
Fort Keogh Livestock and Range Research Laboratory, United States Department of Agriculture Agricultural Research Service, Miles City, MT 59301.
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1749-E1758. doi: 10.1073/pnas.1721191115. Epub 2018 Feb 5.
A major unresolved issue is how the uterus influences infertility and subfertility in cattle. Serial embryo transfer was previously used to classify heifers as high-fertile (HF), subfertile (SF), or infertile (IF). To assess pregnancy loss, two in vivo-produced embryos were transferred into HF, SF, and IF heifers on day 7, and pregnancy outcome was assessed on day 17. Pregnancy rate was substantially higher in HF (71%) and SF (90%) than IF (20%) heifers. Elongating conceptuses were about twofold longer in HF than SF heifers. Transcriptional profiling detected relatively few differences in the endometrium of nonpregnant HF, SF, and IF heifers. In contrast, there was a substantial difference in the transcriptome response of the endometrium to pregnancy between HF and SF heifers. Considerable deficiencies in pregnancy-dependent biological pathways associated with extracellular matrix structure and organization as well as cell adhesion were found in the endometrium of SF animals. Distinct gene expression differences were also observed in conceptuses from HF and SF animals, with many of the genes decreased in SF conceptuses known to be embryonic lethal in mice due to defects in embryo and/or placental development. Analyses of biological pathways, key players, and ligand-receptor interactions based on transcriptome data divulged substantial evidence for dysregulation of conceptus-endometrial interactions in SF animals. These results support the ideas that the uterus impacts conceptus survival and programs conceptus development, and ripple effects of dysregulated conceptus-endometrial interactions elicit loss of the postelongation conceptus in SF cattle during the implantation period of pregnancy.
一个尚未解决的主要问题是子宫如何影响牛的不孕和不育。以前使用连续胚胎移植将小母牛分类为高生育力（HF）、低生育力（SF）或不育（IF）。为了评估妊娠损失，将两个体内产生的胚胎在第 7 天转移到 HF、SF 和 IF 小母牛中，并在第 17 天评估妊娠结果。HF（71%）和 SF（90%）小母牛的妊娠率明显高于 IF（20%）小母牛。伸长的胚胎在 HF 小母牛中比 SF 小母牛长约两倍。转录谱分析检测到非妊娠 HF、SF 和 IF 小母牛的子宫内膜之间差异相对较少。相比之下，HF 和 SF 小母牛的子宫内膜对妊娠的转录组反应存在很大差异。在外层基质结构和组织以及细胞黏附等与妊娠相关的生物学途径中发现了相当大的缺陷在 SF 动物的子宫内膜中。还观察到 HF 和 SF 动物的胚胎之间存在明显的基因表达差异，许多在 SF 胚胎中减少的基因由于胚胎和/或胎盘发育缺陷而在小鼠中是胚胎致死的。基于转录组数据的生物途径、关键参与者和配体-受体相互作用的分析为 SF 动物中胚胎-子宫内膜相互作用的失调提供了大量证据。这些结果支持这样的观点，即子宫影响胚胎的存活并编程胚胎的发育，而失调的胚胎-子宫内膜相互作用的连锁反应会导致 SF 牛在妊娠的延长期丧失延长后的胚胎。
