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Inhibin, activin, follistatin and follicle stimulating hormone serum levels and testicular production are highly modulated during the first spermatogenic wave in mice

B Barakat, Monash Institute of Medical Research, Monash University, Clayton, 3168, Australia
A O'Connor, Monash Institute of Medical Research, Monash University, Clayton, Australia
E Gold, Monash Institute of Medical Research, Monash University, Clayton, Australia
D de Kretser, Monash Institute of Medical Research, Monash University, Clayton, Australia
K Loveland, Centre for Molecular Reproduction and Endocrinology and The ARC Centre of Excellence in Biotechnology and Development, Monash Institute of Reproduction and Development, Clayton, Australia

Correspondence: Badia Barakat, Email: badia.barakat{at}med.monash.edu.au

Abstract

Testicular development is governed by the combined influence of hormones and proteins, including FSH, inhibins, activins and follistatin. This study documents the expression of these proteins and their corresponding mRNA in testes and serum from mice aged 0 through 91 days postpartum (dpp), using real-time PCR, in situ hybridisation, immunohistochemistry, ELISA and radioimmunoassay. Serum immunoactive total inhibin and FSH levels were negatively correlated during development, with FSH levels rising and inhibin levels falling. Activin A production changed significantly during development, with subunit mRNA and protein levels declining rapidly after 4 dpp, while simultaneously, levels of the activin antagonists, follistatin and inhibin/activin βC, increased. Inhibin/activin βA and βB subunit mRNAs were detected in Sertoli, germ and Leydig cells throughout testis development, with the βA subunit also detected in peritubular myoid cells. The , βA, βB, and βC subunit proteins were detected in Sertoli and Leydig cells of developing and adult mouse testes. While βA and βB subunit proteins were observed in spermatogonia and spermatocytes in immature testes, βC was localised to leptotene and zygotene spermatocytes in immature and adult testes. Nuclear βA subunit protein was observed in primary spermatocytes and nuclear βC subunit in gonocytes and round spermatids. The changing spatial and temporal distribution of inhibins and activins indicates that their modulated synthesis and action are important during onset of murine spermatogenesis. This study provides a foundation for evaluation of these proteins in mice with disturbed testicular development, enabling their role in normal and perturbed spermatogenesis to be more fully understood.