Journal Article

Follicle-stimulating hormone-mediated decline in miR-92a-3p expression in pubertal mice Sertoli cells is crucial for germ cell differentiation and fertility

Ghosal, Anindita, Majumdar, Subeer S., Vats, Amandeep, Sarkar, Rajesh, Bhattacharya, Indrashis, Das, Sanjeev, Gupta, Alka, Mandal, Kamal, Pal, Rahul

2022

Overview

Sertoli cells (Sc) are the sole target of follicle-stimulating hormone (FSH) in the testis and attain functional maturation post-birth to significantly augment germ cell (Gc) division and differentiation at puberty. Despite having an operational microRNA (miRNA) machinery, limited information is available on miRNA-mediated regulation of Sc maturation and male fertility. We have shown before that miR-92a-3p levels decline in pubertal rat Sc. In response to FSH treatment, the expressions of FSH Receptor , Claudin11 and Klf4 were found to be elevated in pubertal rat Sc coinciding with our finding of FSH-induced decline in miR-92a-3p levels. To investigate the association of miR-92a-3p and spermatogenesis, we generated transgenic mice where such pubertal decline of miR-92a-3p was prevented by its overexpression in pubertal Sc under proximal Rhox5 promoter, which is known to be activated specifically at puberty, in Sc. Our in vivo observations provided substantial evidence that FSH-induced decline in miR-92a-3p expression during Sc maturation acts as an essential prerequisite for the pubertal onset of spermatogenesis. Elevated expression of miR-92a-3p in post-pubertal testes results into functionally compromised Sc, leading to impairment of the blood–testis barrier formation and apoptosis of pre-meiotic Gc, ultimately culminating into infertility. Collectively, our data suggest that regulation of miR-92a-3p expression is crucial for Sc-mediated induction of active spermatogenesis at puberty and regulation of male fertility. Graphical abstract

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: Animals / Apoptosis / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cell Biology / Cell Differentiation / decline / Differentiation (biology) / Female / Fertility / Follicle Stimulating Hormone - pharmacology / Follicle-stimulating hormone / follicle-stimulating hormone receptors / Follicles / germ cells / Germ Cells - cytology / Germ Cells - drug effects / Germ Cells - metabolism / Hormones - pharmacology / Infertility / KLF4 protein / Life Sciences / Male / male fertility / Males / Maturation / Meiosis / Mice / Mice, Transgenic / microRNA / MicroRNAs / MicroRNAs - genetics / miRNA / Original / Original Article / Puberty / Rats / Rats, Wistar / Receptors, FSH - genetics / Receptors, FSH - metabolism / Ribonucleic acid / RNA / Sertoli cells / Sertoli Cells - cytology / Sertoli Cells - drug effects / Sertoli Cells - metabolism / Sexual Maturation / Spermatogenesis / Testes / Testis - cytology / Testis - drug effects / Testis - metabolism / Transgenic mice