Estrogen Regulated Genes in Rat Testes and Their Relationship to Recovery of Spermatogenesis after Irradiation.

Abstract

Despite numerous observations of the effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. Using rats in which irradiation had completely blocked spermatogonial differentiation, we previously showed that testosterone suppression with gonadotropinreleasing hormone-antagonist acyline and the antiandrogen flutamide stimulated spermatogenic recovery and that addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and using concurrent data on regulation of the genes by these hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or testosterone changes. Expression of 20 genes, largely in somatic cells, was up-or downregulated between 2-and 5-fold by E2. The unexpected and striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes suggested that these might represent noncoding mRNAs; indeed, we have identified several as miRNAs and their potential target genes in this system. We propose that genes for which expression levels are altered in one direction by irradiation and in the opposite direction by both testosterone suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.

Oestrogens as apoptosis regulators in mammalian testis: angels or devils?

“…107), and involves important changes in the expression of oestrogen-target genes (Ref. 108). Although this study has provided a valuable list of candidate genes, the identification of the molecular pathways underpinning the effect of oestrogens in the onset of spermatogenesis is still in the infancy.…”

The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1

“…Although some putative direct target genes of E 2 have been found in the testis [7][8][9], up to now the identification of a testicular cell-specific ER responsive promoter has not been reported. In this investigation, we identified fatty acid amide hydrolase (FAAH) as a direct target gene of E 2 in mouse Sertoli cells.…”