Sertoli Cell Alterations in Peripubertal Varicocelized Rats: Evidence of Primary Damage on Spermatogenesis.

Idiopathic varicocele is closely associated with male infertility or subfertility. Sertoli cell is a very important regulator of spermatogenesis. We investigated the morphofunctional alterations in the Sertoli cell and its possible involvement in the establishment of testicular primary lesion in experimental left-sided varicocele, induced from peripuberty. Twenty-five male peripubertal rats (44 days postpartum [dpp]) were distributed into two groups: control (C) and varicocele (V). Experimental left varicocele was induced in rats through the partial ligature of the left renal vein. Euthanasia was performed at 100 dpp. Testicular histopathology and testosterone plasmatic level were evaluated. Transferrin and vimentin proteins were, respectively, used as immunomarkers of Sertoli cell function and structure. Significant reductions in vimentin and transferrin expressions were noticed in androgen-dependent stages (VII and VIII) of the seminiferous epithelium cycle in V rats; testosterone plasmatic level was also reduced. Bilateral testicular histopathological alterations were found in V rats, mainly massive germ cell desquamation. The histological damage and changes in protein expressions occurred bilaterally. The relevant impairment of the functional and structural characteristics of the Sertoli cell, together with the typical massive germ cell desquamation, indicates that Sertoli cell changes can primarily contribute to the significant testicular dysfunction associated with varicocele.

Vitamin B12 Prevents Cimetidine-Induced Androgenic Failure and Damage to Sperm Quality in Rats.

Cimetidine, used as an anti-ulcer and adjuvant treatment in cancer therapy, causes disorders in the male reproductive tract, including steroidogenesis. However, its effect on sperm quality and male fertility has been poorly addressed. Since vitamin B12 has demonstrated to recover spermatogonia number and sperm concentration in cimetidine-treated rats, we evaluated the impact of cimetidine on sperm quality and fertility potential and whether vitamin B12 is able to prevent the harmful effect of this drug on steroidogenesis and sperm parameters. Adult male rats were treated for 52 consecutive days as follows: cimetidine group (100 mg/kg of cimetidine), cimetidine/vitamin B12 group (100 mg/kg of cimetidine + 3 µg vitamin B12), vitamin B12 group (3 µg vitamin B12) and control group (saline). Serum testosterone levels and immunofluorescence associated to western blot for detection of 17ß-HSD6 were performed. Sperm morphology and motility, mitochondrial activity, acrosome integrity, DNA integrity by Comet assay, lipid peroxidation as well as fertility potential were analyzed in all groups. Apoptotic spermatids were also evaluated by caspase-3 immunohistochemistry. In the cimetidine-treated animals, reduced serum testosterone levels, weak 17ß-HSD6 levels and impaired spermiogenesis were observed. Low sperm motility and mitochondrial activity were associated with high percentage of sperm tail abnormalities, and the percentage of spermatozoa with damaged acrosome and DNA fragmentation increased. MDA levels were normal in all groups, indicating that the cimetidine-induced changes are associated to androgenic failure. In conclusion, despite the fertility potential of rats was unaffected by the treatment, the sperm quality was significantly impaired. Therefore, considering a possible sperm-mediated transgenerational inheritance, the long term offspring health needs to be investigated. The administration of vitamin B12 to male rats prevents the androgenic failure and counteracts the damage inflicted by cimetidine upon sperm quality, indicating that this vitamin may be used as a therapeutic agent to maintain the androgenic status and the sperm quality in patients exposed to androgen disrupters.