Conditional Deletion of FOXL2 and SMAD4 in Gonadotropes of Adult Mice Causes Isolated FSH Deficiency

• DOI: 10.1210/en.2018-00100
• Publication Date: 2018-05-23T18:06:35Z
• Authors: Yining Li; Gauthier Schang; Ying Wang; Xiang Zhou; Adrien Levasseur; Alexandre Boyer; Chu-Xia Deng; Mathias Treier; Ulrich Boehm; Derek Boerboom; Daniel J Bernard
• Keywords: Forkhead Box Protein L2; Male; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Gonadotrophs; Oligospermia; Flow Cytometry; Immunohistochemistry; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals; Female; Follicle Stimulating Hormone; Smad4 Protein

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