Suppression of Sertoli cell tumour development during the first wave of spermatogenesis in inhibin α-deficient mice
Jenna T. Haverfield A B , Peter G. Stanton A C , Kate L. Loveland A B C , Heba Zahid A D , Peter K. Nicholls A C , Justine S. Olcorn A C , Yogeshwar Makanji A , Catherine M. Itman E , Evan R. Simpson A C and Sarah J. Meachem A B FA Hudson Institute of Medical Research, 27–31 Wright Street, Clayton, Vic. 3168, Australia.
B Department of Anatomy and Developmental Biology, Monash University, Wellington Road and Blackburn Road, Clayton, Vic. 3800, Australia.
C Department of Biochemistry and Molecular Biology, Monash University, Wellington Road and Blackburn Road, Clayton, Vic. 3800, Australia.
D Faculty of Applied Medical Science, Taibah University, Al Madinah Al Monawarah, Universities Road, Medina, 30001, Saudi Arabia.
E Priority Research Centres for Reproductive Science and Chemical Biology, School of Environmental and Life Sciences, Faculty of Science and Information Technology, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.
F Corresponding author. Email: sarah.meachem@princehenrys.org
Reproduction, Fertility and Development 29(3) 609-620 https://doi.org/10.1071/RD15239
Abstract
A dynamic partnership between follicle-stimulating hormone (FSH) and activin is required for normal Sertoli cell development and fertility. Disruptions to this partnership trigger Sertoli cells to deviate from their normal developmental pathway, as observed in inhibin α-knockout (Inha-KO) mice, which feature Sertoli cell tumours in adulthood. Here, we identified the developmental windows by which adult Sertoli cell tumourigenesis is most FSH sensitive. FSH was suppressed for 7 days in Inha-KO mice and wild-type littermates during the 1st, 2nd or 4th week after birth and culled in the 5th week to assess the effect on adult Sertoli cell development. Tumour growth was profoundly reduced in adult Inha-KO mice in response to FSH suppression during Weeks 1 and 2, but not Week 4. Proliferative Sertoli cells were markedly reduced in adult Inha-KO mice following FSH suppression during Weeks 1, 2 or 4, resulting in levels similar to those in wild-type mice, with greatest effect observed at the 2 week time point. Apoptotic Sertoli cells increased in adult Inha-KO mice after FSH suppression during Week 4. In conclusion, acute FSH suppression during the 1st or 2nd week after birth in Inha-KO mice profoundly suppresses Sertoli cell tumour progression, probably by inhibiting proliferation in the adult, with early postnatal Sertoli cells being most sensitive to FSH action.
Additional keywords: FSH, cancer, testis.
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