Alpha-fetoprotein Controls Female Fertility and Prenatal Development of the Gonadotropin-releasing Hormone Pathway Through an Antiestrogenic Action

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Feb 16

PMID 16479017

Citations 23

Authors

Christelle De Mees

Jean-Francois Laes

Julie Bakker

Johan Smitz

Benoit Hennuy

Pascale Van Vooren

Philippe Gabant

Josiane Szpirer

Claude Szpirer

Affiliations

Soon will be listed here.

Abstract

It has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the gonadotropin-releasing hormone pathway, which are underexpressed. In the hypothalamus, the gonadotropin-releasing hormone gene, Gnrh1, was also found to be down-regulated. However, pituitary gene expression could be normalized and fertility could be rescued by blocking prenatal estrogen synthesis using an aromatase inhibitor. These results show that AFP protects the developing female brain from the adverse effects of prenatal estrogen exposure and clarify a long-running debate on the role of this fetal protein in brain sexual differentiation.

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