Morpho-functional characteristic of estrogen action on mammalian spermatogenesis

Abstract

The present study deals with mechanisms of estrogen action on male germ cell (GC) development. Experimental approach was developed to manipulate neonatal hormonal environment by single or combined treatment with estrogens (at different doses), GnRH, antiandrogens and phytoestrogens. Experimental model was applied in common marmoset monkeys that were fed neonatally with soy formula milk. Quantitative study of different GC types in tandem with supporting function of the Sertoli cells (SCs) was performed. Specific biomarkers of testicular cells involved in the regulation of spermatogenesis ware investigated. It was found that neonatal estrogen treatment affects spermatogenesis suppressing spermatogonial differentiation by direct mechanism. Meiotic and postmeiotic GC stages are changed by direct estrogen action, as well. More differentiated meiotic (pachytene spermatocytes) and postmeiotic stages (elongated spermatids) are more sensitive to hormonal manipulations. Differential effects of DES and GnRHa on spermatogonia, spermatocytes and spermatids and their subtypes demonstrated differential sensitivity of mitotic, meiotic and posmeiotic stages of spermatogenesis to neonatal hormonal dis-balance.Investigation on expression of retinoic acid receptor-α in Sertoli cells under experimental conditions suggested a possible interplay between retinoid and androgen signaling in SC in the differentiation of GC. The anti-androgenic effect of estrogens on meiotic GC is probably mediated by augmentation of retinoic acid receptor α expression.Two germ cell specific markers were expressed in a stage specific manner - protein p63 in meiotic pachytene spermatocytes and testicular angiotensin-converting enzyme in elongating stages of postmeiotic spermatids.Soy-rich food does not exert dramatically adverse reproductive consequences on marmosets although these `positive` changes should be interpreted carefully as they interfere with hormonal balance and thus growth and/or development of the organism.In conclusion, our complex study provides new understanding about precise mechanisms (direct and indirect) of estrogens on different stages of germ cell differentiation and on Seroli cell supportive function and maturation.