4.5 Article

Progesterone receptor membrane components: key regulators of fetal membrane integrity

期刊

BIOLOGY OF REPRODUCTION
卷 104, 期 2, 页码 445-456

出版社

OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioaa192

关键词

amnion membrane; progesterone; functional progesterone withdrawal; PGRMC2; PGRMC1; preterm birth; pPROM

资金

  1. National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH) of the United States [T32ES007254]
  2. National Institute of Child Health and Human Development (NICHD) [1R03HD098469-01]

向作者/读者索取更多资源

The study reveals that progesterone interacts with PGRMCs to maintain fetal membrane integrity, while oxidative stress decreases endogenous progesterone production and reduces PGRMC expression. These changes may lead to fetal membrane-specific functional progesterone withdrawal.
Pro-pregnancy hormone progesterone (P4) helps to maintain a quiescent status of uterine tissues during gestation. However, P4's functional role in maintaining fetal membrane (amniochorion) integrity remains unclear. P4 functions through its membrane receptors (progesterone receptor membrane components (PGRMCs)) as fetal membrane cells lack nuclear receptors. This study screened the differential expression of PGRMCs in the fetal membranes and tested P4-PGRMC interactions under normal and oxidative stress (OS) conditions expected that can disrupt P4-PGRMC interactions impacting fetal membrane stability resulting in parturition. Human fetal membranes were collected from term and preterm deliveries (N = 5). Immunohistochemistry and western blot localized and determined differential expression of P4 receptors. Primary amnion epithelial, mesenchymal (AMCs), and chorion cell were treated with P4 alone or co-treated (P4 + OS induced by cigarette smoke extract (CSE)). Proximity ligation assay (PLA) documented P4-receptor binding, whereas P4 enzyme-linked immunosorbent assay documented culture supernatant levels. Immunohistology confirmed lack of nuclear progesterone receptors; however, confirmed expressions of PGRMC 1 and 2. Term labor (P = 0.01) and preterm rupture (P = 0.01) are associated with significant downregulation of PGRMC2. OS-induced differential downregulation of PGRMCs in both amnion and chorion cells (all P < 0.05) and downregulates P4 release (AMCs; P = 0.01). The PLA showed preferential receptor-ligand binding in amnion and chorion cells. Co-treatment of P4 + CSE did not reverse CSE-induced effects. In conclusion, P4-PGRMCs interaction maintains fetal membranes' functional integrity throughout pregnancy. Increased OS reduces endogenous P4 production and cell type-dependent downregulation of PGRMCs. These changes can lead to fetal membrane-specific functional progesterone withdrawal, contributing to the dysfunctional fetal membrane status seen at term and preterm conditions.

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