Melatonin up-regulates the expression of the GATA-4 transcription factor and increases testosterone secretion from Leydig cells through RORα signaling in anin vitrogoat spermatogonial stem cell differentiation culture system

Abstract

Because androgen function is regulated by its receptors, androgen-androgen receptor signaling is crucial for regulating spermatogenesis. Androgen is mainly testosterone secreted by testis. Based on the results of early studies in goats, the administration of melatonin over an extended period of time increases steroid production, but the underlying mechanism remains unclear. Here, we report the expression of the melatonin membrane receptors MT1 and MT2 and the retinoic acid receptor-related orphan receptor-alpha (RORα) in the goat testis. An in vitro differentiation system using spermatogonial stem cells (SSCs) cultured in the presence of testicular somatic cells was able to support the formation of sperm-like cells with a single flagellum. The addition of 10-7 M melatonin to the in vitro culture system increased RORα expression and considerably improved the efficiency of haploid cell differentiation, and the addition of the RORα agonist CGP52608 significantly increased the testosterone concentration and expression of GATA binding factor 4 (GATA-4). Furthermore, inhibitors of melatonin membrane receptors and a RORα antagonist (T0901317) also led to a considerable reduction in the efficiency of haploid spermatid formation, which was coupled with the suppression of GATA-4 expression. Based on these results, RORα may play a crucial role in enhancing melatonin-regulated GATA-4 transcription and steroid hormone synthesis in the goat spermatogonial stem cell differentiation culture system.

Insertion/Deletion Within the KDM6A Gene Is Significantly Associated With Litter Size in Goat

“…The analysis results indicate that the 16 bp indel was very strongly associated with goat first-born litter size. Compared with direct analysis in the tested population (Deng et al, 2017a ), this new strategy may provide more detailed and reliable results of association analysis. Additionally, the 16 bp locus had a significant effect on KDM6A gene expression, further implying a huge potential application for analysis of this locus.…”

Lack of retinoid acid receptor-related orphan receptor alpha accelerates and melatonin supplementation prevents testicular aging

“…Expression of RORα nuclear receptors were reported in various tissues including testis, where a relationship between Sertoli cells functions and RORα was detected [ 36 ]. Furthermore, RORα expression and melatonin membrane receptors were recently detected in sheep [ 37 ] and goat [ 38 ] Leydig cells. In the present study, Retinoid-related orphan receptor (RORα)-deficient mice showed age-related progressive damage in the testis tubules and interstitium as well as a massive degeneration in spermatids that lead to decrease in the number of sperms.…”

“…Melatonin increases GATA-4 expression to induce testosterone synthesis by Leydig cells, promoting consequently more active meiosis and spermatid differentiation [ 38 ]. In this regard, the present study revealed an increase in the cellular activity of Leydig cells in the melatonin group, associated with an increase in the number of mitochondria and secretory granules.…”

Retinoic acid promotes in vitro development of haploid germ cells from pre-pubertal porcine spermatogenic cells

“…CREB is an important transcription factor that is differentially regulated in various cell types. The cAMP responsive element modulator (CREM) is an important transcriptional activator during spermatogenesis, especially in postmeiotic germ cells [47]. Inactivation of CREM in mice resulted in an increased rate of apoptosis in the round spermatozoon stage, and the simultaneous expression of apoptosis-related genes [48].…”