HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium

Abstract

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

Network Pharmacology and Molecular Docking Approach to Reveal the Immunotherapeutic Mechanism of Cuscutae Semen in Treating Thin Endometrium

“…Hypoxia represents an important microenvironment condition, which contributes to drug resistance in cancers through regulation of signal pathways [ 37 ]. Endometrium is a kind of multicellular tissue, and there may be hypoxia in endometrium during menstruation and implantation [ 38 ]. The transcriptional activation of a series of genes involved in cell proliferation and angiogenesis was conducive to the survival of hypoxia-exposed cell.…”

Uterine bleeding: how understanding endometrial physiology underpins menstrual health

“…Disruptions in these pathways can lead to increased inflammation, resulting in AUB-E 2 . Progesterone withdrawal, and the subsequent inflammatory cascade, culminates in menstruation 94 . Destruction and shedding of the functional layer (bleeding as menstruation) ensue in a piecemeal fashion, leaving a denuded endometrial surface that undergoes concurrent repair 70 .…”

“…This finding was consistent with HIF1α having a key role in the hypoxia-mediated menstrual repair process. The delayed repair in a non-hypoxic mouse model of menstruation could be rescued with a pharmacological compound that stabilizes HIF1α, identifying a potential non-hormonal therapeutic target in women with AUB-E 94 .…”

Hypoxia and reproductive health

“…This series contains seven diverse and impactful reviews of hypoxia and its potential role in reproductive function. We start the series with a review of the presence and role of hypoxia in the non-pregnant endometrium by Martínez-Aguilar et al (2021). This addresses the controversial question of whether hypoxia actually occurs during the menstrual cycle and, if so, its role in the essential endometrial functions of implantation and menstruation.…”