Division of Animal Sciences, University of Missouri, Columbia, MO 65211.
Division of Animal Sciences, University of Missouri, Columbia, MO 65211;
Proc Natl Acad Sci U S A. 2021 Apr 13;118(15). doi: 10.1073/pnas.2026804118.
Suboptimal uterine fluid (UF) composition can lead to pregnancy loss and likely contributes to offspring susceptibility to chronic adult-onset disorders. However, our understanding of the biochemical composition and mechanisms underpinning UF formation and regulation remain elusive, particularly in humans. To address this challenge, we developed a high-throughput method for intraorganoid fluid (IOF) isolation from human endometrial epithelial organoids. The IOF is biochemically distinct to the extraorganoid fluid (EOF) and cell culture medium as evidenced by the exclusive presence of 17 metabolites in IOF. Similarly, 69 metabolites were unique to EOF, showing asymmetrical apical and basolateral secretion by the in vitro endometrial epithelium, in a manner resembling that observed in vivo. Contrasting the quantitative metabolomic profiles of IOF and EOF revealed donor-specific biochemical signatures of organoids. Subsequent RNA sequencing of these organoids from which IOF and EOF were derived established the capacity to readily perform organoid multiomics in tandem, and suggests that transcriptomic regulation underpins the observed secretory asymmetry. In summary, these data provided by modeling uterine luminal and basolateral fluid formation in vitro offer scope to better understand UF composition and regulation with potential impacts on female fertility and offspring well-being.
子宫液（UF）组成不佳可导致妊娠丢失，并可能导致后代易患慢性成年发病的疾病。然而，我们对 UF 形成和调节的生化组成和机制的理解仍然难以捉摸，特别是在人类中。为了解决这一挑战，我们开发了一种从人子宫内膜上皮类器官中分离类器官内液（IOF）的高通量方法。IOF 在生化上不同于类器官外液（EOF）和细胞培养基，这一点可由 IOF 中仅存在 17 种代谢物证明。同样，EOF 中也有 69 种代谢物是独特的，表明体外子宫内膜上皮细胞以类似于体内观察到的方式，以不对称的顶侧和基底外侧分泌方式分泌。比较 IOF 和 EOF 的定量代谢组学图谱，揭示了类器官的供体特异性生化特征。随后对从中分离出 IOF 和 EOF 的这些类器官进行 RNA 测序，确立了能够轻松地串联进行类器官多组学的能力，并表明转录组调节是观察到的分泌不对称的基础。总之，这些通过体外模拟子宫腔和基底外侧液形成获得的数据提供了更好地理解 UF 组成和调节的范围，这可能对女性生育能力和后代健康产生影响。
