: Hydroxysteroid (17beta) dehydrogenase 1 (Hsd17b1) is a steroidogenic enzyme catalyzing the conversion of estrone (E1) to estradiol (E2), and androstenedione (A-dione) to testosterone (T). We have shown that the deletion of Hsd17b1 gene in mice resulted in the failure of ovarian estrogen production and subfertility. In this study, we clarified the role of Hsd17b1 in male reproduction. The data revealed that in mice Hsd17b1 mRNA is highly expressed in the Sertoli cells at the fetal age. The Sertoli cell function is critical for normal spermatogenesis, and their action is dependent on the pituitary gonadotropins and testosterone. The breeding tests revealed that the Hsd17b1 knockout male mice (HSD17B1KO) were infertile. Because the Hsd17b1 is part of the steroid synthesis machinery, we analyzed the in vivo biomarkers for androgen action, while no changes were observed in fetal masculinization or in onset of puberty. Furthermore, the weights of androgen-dependent tissues in HSD17B1KO were neither affected. Also, the serum gonadotropin levels and the steroid concentrations in the testis, were close to normal in the HSD17B1KO males, with minor changes in the E1/E2 and A-dione/T ratios. Interestingly, several steroidogenic genes, Hsd17b3, Star, Cyp11a1 and Hsd3b1, were significantly upregulated in HSD17B1KO testes, suggesting a functional compensation due to the lack of Hsd17b1 activity. Although no marked changes were observed in the hormonal environment, histological analysis of HSD17B1KO testis revealed defects in the organization of differentiating germ cells in the seminiferous epithelium, and major defects in the haploid germ cell differentiation, particularly in the head shaping of elongating spermatids. Consequently, the epididymal sperm count was dramatically reduced in the HSD17B1KO males, and the remaining spermatozoa were morphologically abnormal. These results revealed a novel role for Hsd17b1 in the control of spermatogenesis and male fertility, and suggest that Hsd17b1 is required for a proper function of Sertoli cells.
20 - 23 May 2017
European Society of Endocrinology