Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Endocrinology and Reproductive Physiology Program, University of Wisconsin-Madison, Madison, WI, USA.
Biol Reprod. 2021 Jul 2;105(1):148-163. doi: 10.1093/biolre/ioab034.
Understanding luteal maintenance during early pregnancy is of substantial biological and practical importance. Characterizing effects of early pregnancy, however, has historically been confounded by use of controls with potential exposure to early Prostaglandin F2-alpha (PGF) pulses or differences in Corpus Luteum (CL) age. To avoid this, the present study utilized bihourly blood sampling to ensure control CL (n = 6) were of a similar age to CL from pregnant animals (n = 5), yet without exposure to PGF pulses. Additionally, CL from second month of pregnancy (n = 4) were analyzed to track fate of altered genes after cessation of embryonic interferon tau (IFNT) secretion. The major alteration in gene expression in first month of pregnancy occurred in interferon-stimulated genes (ISGs), with immune/interferon signaling pathways enriched in three independent over-representation analyses. Most ISGs decreased during second month of pregnancy, though, surprisingly, some ISGs remained elevated in the second month even after cessation of IFNT secretion. Investigation of luteolytic genes found few altered transcripts, in contrast to previous reports, likely due to removal of controls exposed to PGF pulses. An exception to this trend was decreased expression of transcription factor NR4A1. Beyond luteolytic genes and ISGs, over representation analyses highlighted the prevalence of altered genes within the extracellular matrix and regulation of Insulin-like growth factor (IGF) availability, confirming results of other studies independent of luteolytic genes. These results support the idea that CL maintenance in early pregnancy is related to lack of PGF exposure, although potential roles for CL expression of diverse ISGs and other pathways activated during early pregnancy remain undefined.
了解妊娠早期黄体的维持具有重要的生物学和实际意义。然而，由于使用了可能接触早期前列腺素 F2-α（PGF）脉冲或黄体（CL）年龄差异的对照，早期妊娠的特征在历史上一直受到混淆。为了避免这种情况，本研究利用每两小时一次的血液采样来确保对照 CL（n=6）与妊娠动物的 CL（n=5）具有相似的年龄，而不会接触到 PGF 脉冲。此外，还分析了来自妊娠第二个月的 CL（n=4），以追踪胚胎干扰素 tau（IFNT）分泌停止后改变的基因的命运。妊娠第一个月基因表达的主要变化发生在干扰素刺激基因（ISGs）中，三个独立的过表达分析富集了免疫/干扰素信号通路。然而，大多数 ISGs 在第二个月下降，尽管令人惊讶的是，一些 ISGs 在 IFNT 分泌停止后甚至在第二个月仍保持升高。对黄体溶解基因的研究发现，与以前的报告相比，很少有改变的转录本，这可能是由于去除了接触 PGF 脉冲的对照。这种趋势的一个例外是转录因子 NR4A1 的表达减少。除黄体溶解基因和 ISGs 外，过表达分析强调了细胞外基质和胰岛素样生长因子（IGF）可用性调节中改变基因的普遍性，证实了其他研究结果与黄体溶解基因无关。这些结果支持妊娠早期 CL 维持与缺乏 PGF 暴露有关的观点，尽管 CL 表达不同 ISGs 和其他在妊娠早期激活的途径的潜在作用仍未定义。
