Stalling of the endometrial decidual reaction determines the recurrence risk of miscarriage
Brosens, Jan
Brosens, Jan
Abstract
In every menstrual cycle, progesterone acting on estrogen-primed endometrium elicits an
inflammatory decidual reaction, rendering it poised for embryo implantation and
transformation into the decidua of pregnancy. Here, we show that the sequential functions of
the decidual reaction - implantation and decidualization - pivot on the time-sensitive loss of
progesterone-resistant DIO2+ stromal cells that form a specialized implantation niche and
reciprocal expansion of progesterone-dependent PLA2G2A+ pre-decidual cells.
Simultaneously, uterine natural killer (uNK) cell proliferation results in the accumulation of
immunotolerant subsets. Examination of endometrial biopsies from 924 women revealed that
the recurrence risk of miscarriage closely aligns with the incidence of a weakened or stalled
decidual reaction, more so than poor uNK cell expansion. Analysis of paired biopsies obtained
in different cycles and modeling in assembloids intimated that prior miscarriages disrupt
intercycle endometrial homeostasis and calibration of the decidual reaction. Our findings show
that erosion of the decidual reaction following a miscarriage drives the recurrence risk
irrespective of maternal age.
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Date
2025
Type
Article
Subject
Collections
Citation
: Joanne Muter1,2 †, Chow-Seng Kong1 †,Mireia Taus Nebot1 ,Maria Tryfonos1,3 , Pavle Vrljicak1 ‡, Paul J. Brighton1 , Danai B. Dimakou4 , Megan Vickers1 , Hiroyuki Yoshihara1 §, Sascha Ott1 , Bee K. Tan5 , Phillip R. Bennett5 , Siobhan Quenby1,2, Alex Richter4 , Hilde Van de Velde3 , Emma S. Lucas1 ¶, Thomas M. Rawlings1 , and Jan J. Brosens1,2*
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DOI
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Publisher
Science Family of Journals