Department of Large Animal Clinical Sciences, University of Tennessee, Knoxville, Tennessee, USA.
Center for Species Survival, Smithsonian Conservation Biology Institute, Front Royal, Virginia, USA.
Reproduction. 2020 Dec;160(6):819-831. doi: 10.1530/REP-20-0266.
The endometrium, the inner uterine lining, is composed of cell layers that come in direct contact with an embryo during early pregnancy and later with the fetal placenta. The endometrium is responsible for signals associated with normal reproductive cyclicity as well as maintenance of pregnancy. In the mare, functionally competent in vitro models of the endometrium have not been successful. Furthermore, the ability to study various reproductive processes in vitro may allow critical evaluation of signaling pathways involved in the reproductive diseases of animals that cannot be handled frequently, such as various wildlife species. Here we report the establishment of organoids, 3D structures, derived from fresh and frozen-thawed equine endometrium (Equus ferus caballus and E. f. przewalskii). Although organoids from domestic mares responded to exogenous hormonal stimuli, organoids from Przewalski's horse failed to respond to exogenous hormones. The present study represents a 'first' for any large animal model or endangered species. These physiologically functional organoids may facilitate improved understanding of normal reproductive mechanisms, uterine pathologies, and signaling mechanisms between the conceptus and endometrium and may lead to the development of novel bioassays for drug discovery.
子宫内膜是子宫内的衬里，由直接与胚胎接触的细胞层组成，在怀孕早期，后来与胎儿胎盘接触。子宫内膜负责与正常生殖周期性相关的信号以及妊娠的维持。在母马中，功能上能够胜任的子宫内膜体外模型尚未成功建立。此外，在体外研究各种生殖过程的能力可能允许对涉及动物生殖疾病的信号通路进行关键评估，这些动物疾病不能频繁处理，例如各种野生动物物种。在这里，我们报告了从新鲜和冷冻解冻的马子宫内膜（Equus ferus caballus 和 E. f. przewalskii）中衍生的类器官（3D 结构）的建立。尽管来自家马的类器官对外源激素刺激有反应，但来自普氏野马的类器官对外源激素没有反应。本研究代表了任何大型动物模型或濒危物种的“首例”。这些具有生理功能的类器官可能有助于更好地理解正常生殖机制、子宫病理学以及胚胎和子宫内膜之间的信号机制，并可能导致新的药物发现生物测定的开发。
