美国加州大学圣迭戈分校Adrian Erlebacher小组发现，KDM6B依赖的子宫成纤维细胞早期妊娠表观遗传编程调控小鼠分娩时机。2025年1月21日，国际知名学术期刊《细胞》在线发表了这一成果。

通过研究缺乏组蛋白H3K27me3去甲基化酶KDM6B的子宫成纤维细胞的小鼠延迟分娩表型，研究人员提供了证据表明，分娩时机受早期妊娠期间发生的事件调控。交配后，子宫成纤维细胞启动了一个特定位点的表观遗传程序，迅速调整其基因组中H3K27me3水平。在缺乏KDM6B的情况下，许多调整过的位点过度积累H3K27me3。

这种过度积累导致在妊娠中期至晚期，邻近基因发生误表达，这种延迟效应部分可归因于一个独立于KDM6B的、在着床后不久在子宫成纤维细胞内启动的第二个位点特异性过程。这个第二个过程通过逐步丧失H3K27me3，时间性地构建了妊娠中期后的基因诱导模式。进一步剖析子宫编程如何调控分娩时机，可能与人类妊娠并发症，如早产，具有相关性。

据悉，目前关于分娩时机机制的研究主要集中在妊娠晚期产生的分娩启动近端触发因素。

附：英文原文

Title: KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice

Author: Tara I. McIntyre, Omar Valdez, Nathan P. Kochhar, Brittany Davidson, Bushra Samad, Longhui Qiu, Kenneth Hu, Alexis J. Combes, Adrian Erlebacher

Issue&Volume: 2025-01-21

Abstract: Current efforts investigating parturition timing mechanisms have focused on the proximal triggers of labor onset generated in late pregnancy. By studying the delayed parturition phenotype of mice with uterine fibroblast deficiencies in the histone H3K27me3 demethylase KDM6B, we provide evidence that parturition timing is regulated by events that take place in early pregnancy. Immediately after copulation, uterine fibroblasts engage in a locus-specific epigenetic program that abruptly adjusts H3K27me3 levels across their genome. In the absence of KDM6B, many of the adjusted loci over-accumulate H3K27me3. This over-accumulation leads to nearby genes being misexpressed in mid-to-late gestation, a delayed effect partly attributable to a second locus-specific but KDM6B-independent process initiated within uterine fibroblasts soon after implantation. This second process employs progressive H3K27me3 loss to temporally structure post-midgestational patterns of gene induction. Further dissection of the ways uterine programming controls parturition timing may have relevance to human pregnancy complications such as preterm labor.

DOI: 10.1016/j.cell.2024.12.019

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01432-6