Maurya Vineet K, DeMayo Francesco J, Lydon John P
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, United States.
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC, United States.
Front Cell Dev Biol. 2021 Apr 7;9:640907. doi: 10.3389/fcell.2021.640907. eCollection 2021.
Synchrony between progesterone-driven endometrial receptivity and the arrival of a euploid blastocyst is essential for embryo implantation, a prerequisite event in the establishment of a successful pregnancy. Advancement of embryo implantation within the uterus also requires stromal fibroblasts of the endometrium to transform into epithelioid decidual cells, a progesterone-dependent cellular transformation process termed decidualization. Although progesterone is indispensable for these cellular processes, the molecular underpinnings are not fully understood. Because human studies are restricted, much of our fundamental understanding of progesterone signaling in endometrial periimplantation biology comes from and experimental systems. In this review, we focus on the tremendous progress attained with the use of engineered mouse models together with high throughput genome-scale analysis in disclosing key signals, pathways and networks that are required for normal endometrial responses to progesterone during the periimplantation period. Many molecular mediators and modifiers of the progesterone response are implicated in cross talk signaling between epithelial and stromal cells of the endometrium, an intercellular communication system that is critical for the ordered spatiotemporal control of embryo invasion within the maternal compartment. Accordingly, derailment of these signaling systems is causally linked with infertility, early embryo miscarriage and gestational complications that symptomatically manifest later in pregnancy. Such aberrant progesterone molecular responses also contribute to endometrial pathologies such as endometriosis, endometrial hyperplasia and cancer. Therefore, our review makes the case that further identification and functional analysis of key molecular mediators and modifiers of the endometrial response to progesterone will not only provide much-needed molecular insight into the early endometrial cellular changes that promote pregnancy establishment but lend credible hope for the development of more effective mechanism-based molecular diagnostics and precision therapies in the clinical management of female infertility, subfertility and a subset of gynecological morbidities.
孕酮驱动的子宫内膜容受性与整倍体囊胚的着床同步对于胚胎着床至关重要，而胚胎着床是成功妊娠建立的前提事件。子宫内胚胎着床的推进还需要子宫内膜的基质成纤维细胞转化为上皮样蜕膜细胞，这是一个依赖孕酮的细胞转化过程，称为蜕膜化。尽管孕酮对于这些细胞过程不可或缺，但其分子基础尚未完全了解。由于人体研究受限，我们对子宫内膜着床期生物学中孕酮信号传导的许多基本认识来自于实验系统。在本综述中，我们重点关注利用工程小鼠模型以及高通量基因组规模分析在揭示着床期子宫内膜对孕酮正常反应所需的关键信号、途径和网络方面取得的巨大进展。孕酮反应的许多分子介质和调节剂参与了子宫内膜上皮细胞和基质细胞之间的串扰信号传导，这是一种细胞间通讯系统，对于母体腔内胚胎侵入的有序时空控制至关重要。因此，这些信号系统的紊乱与不孕症、早期胚胎流产以及妊娠后期出现症状的妊娠并发症存在因果关系。这种异常的孕酮分子反应也会导致子宫内膜病变，如子宫内膜异位症、子宫内膜增生和癌症。因此，我们的综述表明，进一步鉴定和功能分析子宫内膜对孕酮反应的关键分子介质和调节剂，不仅将为促进妊娠建立的早期子宫内膜细胞变化提供急需的分子见解，而且为在女性不孕症、亚生育力和一部分妇科疾病的临床管理中开发更有效的基于机制的分子诊断和精准治疗带来可靠希望。
