A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization

Isaac Shaw, Phoebe M. Kirkwood, Diane Rebourcet, Fiona L. Cousins, Rebecca J. Ainslie, Dawn E. W. Livingstone, Lee B. Smith, Philippa T. K. Saunders, Douglas A Gibson
In: Frontiers in Endocrinology · 2022 · vol. 13 , pp. 1027164 · doi:10.3389/fendo.2022.1027164 · PMID:36465608 · W4309315785
article OA: gold CC0 ⤵ 1 in-corpus citation
🔓 Open OA copy View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Steroid 5α-reductase 1 deficiency in mice impaired endometrial decidualization and vascular remodeling by disrupting VEGF signaling, which dihydrotestosterone administration could partially restore.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

The study investigated whether steroid 5α-reductase type 1 (SRD5A1)–dependent intracrine androgen signaling is required for in vivo endometrial decidualization and associated vascular remodeling, using Srd5a1−/− mice and a hormone-induced model of decidualization. Decidualization outcomes (response scoring and uterine tissue measurements), vascular morphology/function (including vessel permeability), and transcriptomic changes in angiogenesis-related pathways—especially those involving VEGF—were assessed, with finasteride used to inhibit 5α-reductase activity and dihydrotestosterone (DHT) supplementation used to restore androgen signaling. SRD5A1 deficiency produced impaired decidualization and disrupted vessel permeability and angiogenesis gene regulation, and co-administration of DHT restored these effects toward wild-type levels. The authors explicitly frame this work as confirming a major role for intracrine androgens in decidual vasculature through the VEGF pathway in vivo. This paper is centrally about endometriosis — it analyzes endometrial decidualization biology, including androgen and VEGF-dependent vascular remodeling mechanisms relevant to endometriosis-associated pelvic inflammation and altered endometrial function.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

Decidualization is the hormone-dependent process of endometrial remodeling that is essential for fertility and reproductive health. It is characterized by dynamic changes in the endometrial stromal compartment including differentiation of fibroblasts, immune cell trafficking and vascular remodeling. Deficits in decidualization are implicated in disorders of pregnancy such as implantation failure, intra-uterine growth restriction, and pre-eclampsia. Androgens are key regulators of decidualization that promote optimal differentiation of stromal fibroblasts and activation of downstream signaling pathways required for endometrial remodeling. We have shown that androgen biosynthesis, via 5α-reductase-dependent production of dihydrotestosterone, is required for optimal decidualization of human stromal fibroblasts in vitro , but whether this is required for decidualization in vivo has not been tested. In the current study we used steroid 5α-reductase type 1 (SRD5A1) deficient mice ( Srd5a1-/- mice) and a validated model of induced decidualization to investigate the role of SRD5A1 and intracrine androgen signaling in endometrial decidualization. We measured decidualization response (weight/proportion), transcriptomic changes, and morphological and functional parameters of vascular development. These investigations revealed a striking effect of 5α-reductase deficiency on the decidualization response. Furthermore, vessel permeability and transcriptional regulation of angiogenesis signaling pathways, particularly those that involved vascular endothelial growth factor (VEGF), were disrupted in the absence of 5α-reductase. In Srd5a1-/- mice, injection of dihydrotestosterone co-incident with decidualization restored decidualization responses, vessel permeability, and expression of angiogenesis genes to wild type levels. Androgen availability declines with age which may contribute to age-related risk of pregnancy disorders. These findings show that intracrine androgen signaling is required for optimal decidualization in vivo and confirm a major role for androgens in the development of the vasculature during decidualization through regulation of the VEGF pathway. These findings highlight new opportunities for improving age-related deficits in fertility and pregnancy health by targeting androgen-dependent signaling in the endometrium.

My notes (saved in your browser only)

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (50)

Cited by (1)

Source provenance

openalex
last seen: 2026-06-10T17:14:06.276822+00:00
License: CC0 · commercial use OK