Induction of spermatogenesis by androgens in gonadotropin-deficient (hpg) mice

Abstract

Using a new experimental model for studying the hormonal induction of spermatogenesis, the hpg mouse, which has congenital functional gonadotropin deficiency due to a major deletion in the GnRH gene, we investigated the roles of testosterone (T) and dihydrotestosterone (DHT) in the initiation of spermatogenesis. Weanling homozygous hpg male mice were implanted subdermally with SILASTIC brand implants of varying lengths (0-2 cm) filled with T or DHT, using phenotypically normal (N/N or N/hpg) and untreated hpg/hpg mice as positive and negative controls. After 8 weeks, both T and DHT equally stimulated (approximately 14-fold) testis size and induced qualitatively complete spermatogenesis despite low intratesticular androgen levels and undetectable circulating FSH. Stereological quantitation of Sertoli and germ cells demonstrated a dose-dependent rise in the absolute numbers of all germ cell types induced by both T and DHT. At maximal androgen doses, germ cell numbers expressed per Sertoli cell and homogenization-resistant elongated spermatids expressed per mg testis were increased to more than 80% of non-hpg control values. An in vitro fertilization assay confirmed that both T and DHT induced quantitatively normal fertilizing capacity of the sperm in hpg males. We conclude that androgens, acting through the androgen receptor without need for aromatization, initiate qualitatively complete spermatogenesis in the mouse, including fertile sperm despite low intratesticular androgen levels and the absence of blood FSH levels. The hpg mouse model is a useful new paradigm to study the molecular basis of the hormonal induction of spermatogenesis.

Ginkgo Biloba Ameliorates Subfertility Induced by Testicular Ischemia/Reperfusion Injury in Adult Wistar Rats: A Possible New Mitochondrial Mechanism

“…Reyes et al [43] mentioned that increased testicular temperature might cause the hypoxic changes in the testicles such as increased vascularisation, decreased testicular mass, and increased interstitial space. Therefore, the observed low level of plasma-free testosterone in the ischemia only and I/R groups may be the possible cause of spermatogenic impairment, similar to Singh et al [44], who reported that testosterone was responsible for the activation and maintenance of spermatogenesis. In addition, O'Donnell et al [45] found that testosterone could help in the maturation of round and elongated spermatids.…”

Evidence for increased tissue androgen sensitivity in neurturin knockout mice

“…This is consistent with the retained fertility reported in mature NTNKO and GFRaKO males (Widenfalk et al 2000). The preservation of spermatogenesis despite markedly reduced circulating and intratesticular androgen levels is consistent with the fact that intratesticular testosterone levels required for induction (Singh et al 1995) or maintenance (Handelsman et al 1999) of murine spermatogenesis are much lower than ambient levels prevailing in the testis or bloodstream with analogous findings reported in rats despite a significantly reduced number of seminiferous tubules and interstitial fluid testosterone levels (Zirkin et al 1989). Hence, increased androgen sensitivity in the testis of the NTNKO mice could support the maintenance of normal spermatogenesis despite markedly lowered circulating and intratesticular levels.…”

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

“…Moreover, RGN is underexpressed in breast and prostate cancer cases and E 2 upregulated while DHT downregulated RGN mRNA expression in MCF-7 and LNCaP cell lines, respectively (Maia et al 2009). DHT, a nonaromatizable androgen, has been shown to stimulate spermatogenesis in a similar way to testosterone (Singh et al 1995, Meachem et al 2007, O'Shaughnessy et al 2010, therefore it was used to analyze the effect of androgens on Rgn expression in rat SeT cultured ex vivo. qPCR analysis showed that DHT upregulates Rgn mRNA expression in rat cultured SeT at 24 h of exposure (Fig.…”