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Impaired fertility and FSH synthesis in gonadotrope-specific Foxl2 knockout mice

Item Type:Article
Title:Impaired fertility and FSH synthesis in gonadotrope-specific Foxl2 knockout mice
Creators Name:Tran, S. and Zhou, X. and Lafleur, C. and Calderon, M.J. and Ellsworth, B.S. and Kimmins, S. and Boehm, U. and Treier, M. and Boerboom, D. and Bernard, D.J.
Abstract:Impairments in pituitary FSH synthesis or action cause infertility. However, causes of FSH dysregulation are poorly described, in part because of our incomplete understanding of mechanisms controlling FSH synthesis. Previously, we discovered a critical role for forkhead protein L2 (FOXL2) in activin-stimulated FSH {beta}-subunit (Fshb) transcription in immortalized cells in vitro. Here, we tested the hypothesis that FOXL2 is required for FSH synthesis in vivo. Using a Cre/lox approach, we selectively ablated Foxl2 in murine anterior pituitary gonadotrope cells. Conditional knockout (cKO) mice developed overtly normally but were subfertile in adulthood. Testis size and spermatogenesis were significantly impaired in cKO males. cKO females exhibited reduced ovarian weight and ovulated fewer oocytes in natural estrous cycles compared with controls. In contrast, ovaries of juvenile cKO females showed normal responses to exogenous gonadotropin stimulation. Both male and female cKO mice were FSH deficient, secondary to diminished pituitary Fshb mRNA production. Basal and activin-stimulated Fshb expression was similarly impaired in Foxl2 depleted primary pituitary cultures. Collectively, these data definitively establish FOXL2 as the first identified gonadotrope-restricted transcription factor required for selective FSH synthesis in vivo.
Keywords:Activins, beta Subunit Follicle Stimulating Hormone, Fertility, Forkhead Transcription Factors, Gene Deletion, Gene Expression Regulation, Genetic Loci, Genetic Recombination, Gonadotrophs, Gonadotropins, Messenger RNA, Organ Size, Organ Specificity, Ovarian Follicle, Ovulation, Sertoli Cells, Spermatogenesis, Testis, Animals, Horses, Mice
Source:Molecular Endocrinology
Publisher:Endocrine Society
Page Range:407-421
Date:March 2013
Official Publication:https://doi.org/10.1210/me.2012-1286
PubMed:View item in PubMed

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