Endocrine Disruption of the Follicle-Stimulating Hormone Receptor Signaling During the Human Antral Follicle Growth.

Neena Roy,Elisa Mascolo,Sara D’Alessandro,Elia Paradiso,Manuela Simoni,Kornelia Zaręba,Livio Casarini,Clara Lazzaretti

doi:10.3389/fendo.2021.791763

Abstract

An increasing number of pollutants with endocrine disrupting potential are accumulating in the environment, increasing the exposure risk for humans. Several of them are known or suspected to interfere with endocrine signals, impairing reproductive functions. Follicle-stimulating hormone (FSH) is a glycoprotein playing an essential role in supporting antral follicle maturation and may be a target of disrupting chemicals (EDs) likely impacting female fertility. EDs may interfere with FSH-mediated signals at different levels, since they may modulate the mRNA or protein levels of both the hormone and its receptor (FSHR), perturb the functioning of partner membrane molecules, modify intracellular signal transduction pathways and gene expression. In vitro studies and animal models provided results helpful to understand ED modes of action and suggest that they could effectively play a role as molecules interfering with the female reproductive system. However, most of these data are potentially subjected to experimental limitations and need to be confirmed by long-term observations in human.

Highlights

An increasing number of organic pollutants are accumulating in wastewater and soil
Another study in rat granulosa cells showed that TCDD (10 pM) suppresses the expression and mRNA stability of Folliclestimulating hormone (FSH)-induced luteinizing hormone (LH) receptors, suggesting that TCDD disrupts the signaling pathway that responds to LH-induced ovulation [112]
Environmental pollutants which cause endocrine disruption may impact FSHR signals at different levels. They may target direcly receptors expressed in the surface of ovarian cells, acting as allosteric modulators and binding promiscuity

Summary

Introduction

An increasing number of organic pollutants are accumulating in wastewater and soil. They may not necessarily be eliminated by purification treatments and could be potentially damaging for animals, as well as for human health. The activation of FSHR-mediated intracellular signaling pathways is further modulated by the presence of partner proteins located in the cell membrane, which may form heteromeric complexes perturbing FSH-dependent activity [32, 33]. FSHR/GPER complexes would be present on the surface of primary granulosa cells, where they inhibit the intracellular cAMP accumulation and stimulate proliferative signals activating the AKT pathway upon FSH binding [4, 41].

Results

Conclusion