These studies also show that testosterone affects noradrenaline levels not only in reproductive organs but also in other visceral organs19, although such effects in the spleen have not been described previously. There are small biological variations in BAFF levels in homoeostasis, which may be concordant with a tight regulation of BAFF and that even small alterations may change B cell homoeostasis. There are no data available on the concentration-response relation between local or systemic BAFF levels and B cell numbers in mice. In our study, BAFF levels were modestly increased by testosterone/AR deficiency. Testosterone can also act to regulate spermatogenesis via its non-aromatizable metabolite, Dihydrotestosterone (DHT) and estradiol (E2), its aromatizable metabolite 7, 8. AR blockade reduced the fertility of male rats due to the production of poor quality epididymal spermatozoa, deficient in thiols and protamine1 . Most mammalian species express a testicular protein that specifically binds androgens T/DHT (dihydrotestosterone) with high affinity . Testosterone (T) is a lipophilic steroidal molecule synthesized in the interstitial cells of Leydig in the testis. Throughout this entire process of maturation and differentiation of B cells, self-reactive clones can be generated. The maintenance of the activation of GC-B cells, coupled with the maturation of the affinity and increase of BLIMP-1, IRF4, and XBP1, gives way to the formation of memory B cells or long-lived plasma cells, which travel to bone marrow for the maintenance of immunological memory. The activation of MZ-B or follicular B cells in the absence of cooperation with follicular T cells (TFH) leads to the formation of short-lived plasma cells, the process of which is highly regulated by BLIMP-1. The immature cells migrate to the spleen, and during this stage, they go through transitional cell stages 1 (T1) and 2 (T2) to finally reach the marginal zone (MZ) or the B follicles as mature cells. Approaches such as testicular tissue or SSC transplantation, and in vitro spermatogenesis, are emerging as vital strategies to restore fertility in individuals suffering from conditions like cancer or azoospermia . Nevertheless, the endocrinology of the male reproductive system is particularly critical as it regulates the synthesis of sperm and other male reproductive entities . This complexity is not unique to reproductive biology; for instance, the in vivo intestinal stem cell compartment also illustrates the challenges in capturing physiological interactions within tissues . Hormonal male contraception has been shown to be effective in clinical trials, but a novel male contraceptive will mitigate a myriad of biopsychosocial risks by male users and their partners . It has been proven in clinical trials to be a highly reversible, effective, and safe male contraceptive, with a total efficacy was about 95% . Testosterone undecanoate (TU), a testosterone ester created by the fatty acid esterification of testosterone, has been approved for use in several countries. For example, transcription factors including Krüppel-like factor 4 (KLF4) , nuclear factor (NF)-κB , and activator protein-1 (AP-1) are involved in the regulation of Sertoli cell differentiation by FSH. Furthermore, FSH targets functional factors and transcription factors through the cAMP/PKA pathway to affect Sertoli cell differentiation and apoptosis 76,77. The suppression of FSH in neonates reduces the number of final Sertoli cells by approximately 40% , which in turn affects the quantity of sperm. FSH-induced signal transduction is mediated by FSHR, and its function reliant on interactions with numerous intracellular effectors. Interestingly, the role of androgens in establishing normal reproductive tract development and the masculinization of anogenital distance (AGD) is limited to a specific developmental window, known as the "masculinization programming window" (MPW).
