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Conditional deletion of FOXL2 and SMAD4 in gonadotropes of adult mice causes isolated FSH deficiency
Li Y.2; Schang G.2; Wang Y.2; Zhou X.2; Levasseur A.5; Boyer A.5; Deng C.-X.6; Treier M.3; Boehm U.1; Boerboom D.5; Bernard D.J.2
2018-07-01
Source PublicationEndocrinology
ISSN19457170 00137227
Volume159Issue:7Pages:2641-2655
Abstract

The glycoprotein FSH, a product of pituitary gonadotrope cells, regulates ovarian follicle development in females and spermatogenesis in males. FSH is a heterodimer of the common a gonadotropin subunit and the hormone-specific FSHb subunit (a product of the Fshb gene). Using a conditional knockout approach (Cre-lox), we previously demonstrated that Fshb expression in mice depends on the transcription factors forkhead box L2 (FOXL2) and SMAD4. Deletion of Foxl2 or Smad4 alone led to FSH deficiency, female subfertility, and oligozoospermia in males. Simultaneous deletion of the two genes yielded a greater suppression of FSH and female sterility. The Cre-driver used previously was first active during embryonic development. Therefore, it is unclear whether FOXL2 and SMAD4 play important roles in the development or adult function of gonadotropes, or both. To address this question, we developed a tamoxifen-inducible Cre-driver line, which enabled Foxl2 and Smad4 gene deletions in gonadotropes of adult mice. After tamoxifen treatment, females with previously demonstrated fertility exhibited profound reductions in FSH levels, arrested ovarian follicle development, and sterility. FSH levels were comparably reduced in males 1 or 2 months after treatment; however, spermatogenesis was unaffected. These data indicate that (1) FOXL2 and SMAD4 are necessary to maintain FSH synthesis in gonadotrope cells of adult mice, (2) FSH is essential for female reproduction but appears to be unnecessary for the maintenance of spermatogenesis in adult male mice, and (3) the inducible Cre-driver line developed here provides a powerful tool to interrogate gene function in gonadotrope cells of adult mice.

DOI10.1210/en.2018-00100
URLView the original
Indexed BySCI
Language英语
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000438614000014
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorBernard D.J.
Affiliation1.Universitatsklinikum des Saarlandes Medizinische Fakultat der Universitat des Saarlandes
2.McGill University
3.Max Delbruck Center for Molecular Medicine
4.Charité – Universitätsmedizin Berlin
5.University of Montreal
6.Universidade de Macau
Recommended Citation
GB/T 7714
Li Y.,Schang G.,Wang Y.,et al. Conditional deletion of FOXL2 and SMAD4 in gonadotropes of adult mice causes isolated FSH deficiency[J]. Endocrinology,2018,159(7):2641-2655.
APA Li Y..,Schang G..,Wang Y..,Zhou X..,Levasseur A..,...&Bernard D.J..(2018).Conditional deletion of FOXL2 and SMAD4 in gonadotropes of adult mice causes isolated FSH deficiency.Endocrinology,159(7),2641-2655.
MLA Li Y.,et al."Conditional deletion of FOXL2 and SMAD4 in gonadotropes of adult mice causes isolated FSH deficiency".Endocrinology 159.7(2018):2641-2655.
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