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 Previous Article

Molecular and Cellular Biology, March 2006, p. 2012-2018, Vol. 26, No. 5
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.5.2012-2018.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Alpha-Fetoprotein Controls Female Fertility and Prenatal Development of the Gonadotropin-Releasing Hormone Pathway through an Antiestrogenic Action{dagger}

Christelle De Mees,1* Jean-François Laes,2 Julie Bakker,3 Johan Smitz,4 Benoît Hennuy,2 Pascale Van Vooren,1 Philippe Gabant,2,{ddagger} Josiane Szpirer,1 and Claude Szpirer1

Université Libre de Bruxelles, IBMM, Laboratoire de Biologie du Développement, Rue Pr. Jeener & Brachet 12, B-6041 Gosselies (Charleroi), Belgium,1 Biovallée, Rue A. Bolland 8, B-6041 Gosselies (Charleroi), Belgium,2 Université de Liège, Center for Cellular & Molecular Neurobiology, Avenue de l'Hopital 1, B-4000 Sart Tilman (Liège), Belgium,3 Vrije Universiteit Brussel, Academic Hospital, Radioimmunology and Reproductive Biology, Laarbeeklaan 101, B-1090 Bruxelles, Belgium4

Received 26 August 2005/ Returned for modification 28 October 2005/ Accepted 10 December 2005

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.

* Corresponding author. Mailing address: Université Libre de Bruxelles, IBMM, Laboratoire de Biologie du Développement, Rue Pr. Jeener & Brachet 12, B-6041 Gosselies (Charleroi), Belgium. Phone: 3226509703. Fax: 3226509700. E-mail: cdemees{at}ulb.ac.be.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: DelphiGenetics, Rue A. Bolland 8, B-6041 Gosselies (Charleroi), Belgium.

Molecular and Cellular Biology, March 2006, p. 2012-2018, Vol. 26, No. 5
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.5.2012-2018.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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