Follicle-stimulating hormone induced changes in gene expression of murine testis

Abstract

Even though FSH is not required for qualitatively normal spermatogenesis, it plays an important role in the spermatogenic capacity of the testis. Although the actions of FSH are well documented, most of these studies were done in vitro, and the molecular targets of FSH in vivo remain largely unverified. To understand the complete mechanism of FSH actions in spermatogenesis, it is important to identify the genes that are involved in its signaling, and know how these genes are affected by FSH. We have used hypogonadal (hpg) mouse that lacks circulating FSH as an in vivo model in conjunction with the Affymetrix murine GeneChip U74A (12,488 genes) to monitor changes in testicular gene expression as a result of FSH signaling. Hpg mice were injected with 10 IU ovine FSH, killed 4, 8, 12, or 24 h post treatment, and their testicular gene expression was compared with that of untreated control hpg mice. The abundance of a large number of mRNAs was affected by the FSH treatment. The primary effect of FSH resulted in increased steady-state levels of many mRNAs in testes of hpg mice. Several transcripts were identified whose abundance was decreased as well. We have used real-time PCR to confirm the changes in levels of transcripts such as renin-1, Kruppel-like factor 4, Mad4 (max-interacting protein repressor), Nur-related protein 1, and hairy/enhancer of splits gene 1 that were found to be regulated by FSH in testes of hpg mice.