Defective AMH Signaling Disrupts GnRH Neuron Development and Function and Contributes to Hypogonadotropic Hypogonadism

Overview

Journal Elife

Specialty Biology

Date 2019 Jul 11

PMID 31291191

Citations 35

Authors

Samuel Andrew Malone

Georgios E Papadakis

Andrea Messina

Nour El Houda Mimouni

Sara Trova

Monica Imbernon

Cecile Allet

Irene Cimino

James Acierno

Daniele Cassatella

Cheng Xu

Richard Quinton

Gabor Szinnai

Pascal Pigny

Lur Alonso-Cotchico

Laura Masgrau

Jean-Didier Marechal

Vincent Prevot

Nelly Pitteloud

Paolo Giacobini

Affiliations

Soon will be listed here.

Abstract

Congenital hypogonadotropic hypogonadism (CHH) is a condition characterized by absent puberty and infertility due to gonadotropin releasing hormone (GnRH) deficiency, which is often associated with anosmia (Kallmann syndrome, KS). We identified loss-of-function heterozygous mutations in anti-Müllerian hormone () and its receptor, , in 3% of CHH probands using whole-exome sequencing. We showed that during embryonic development, AMH is expressed in migratory GnRH neurons in both mouse and human fetuses and unconvered a novel function of AMH as a pro-motility factor for GnRH neurons. Pathohistological analysis of -deficient mice showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in reduced fertility in adults. Our findings highlight a novel role for AMH in the development and function of GnRH neurons and indicate that AMH signaling insufficiency contributes to the pathogenesis of CHH in humans.

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