Vol. 32, Nš 3

PPAR ? agonist pioglitazone partially reverses hyperglycemia but improves semen quality and testicular histomorphometrics in alloxan-induced diabetic rats

Akinola, O.; Sanusi, S. A.; Ajayi, T. F.; Olajide, T. H.

KEYWORDS: diabetes mellitus, hyperglycaemia, male infertility, pioglitazone, PPAR gamma.

ABSTRACT: Introduction: Chronic hyperglycaemia is associated with subfertility and infertility in male diabetic subjects, possible as a result of perturbed testicular antioxidant defence system. Recent evidence however shows that some testicular cells produce insulin and this raises the possibility of a role for this hormone in spermatogenesis. Moreover, isoforms of the nuclear peroxisome proliferator activated receptor (PPAR) have been detected in testicular tissue, suggesting a role for insulin sensitization in testicular function. Materials and Methods: In this study, we report the ameliorative effects of the PPAR ? agonist pioglitazone on testicular morphologic aberrations and impaired semen profile induced by diabetes in rats treated with intraperitoneal alloxan (150 mg/kg). Diabetic rats were randomly assigned to receive oral pioglitazone at 10 or 30 mg/kg once daily for 6 weeks. Weekly blood glucose measurement using the glucometer showed weak effect of pioglitazone on hyperglycaemia in our model. Results: Nonetheless, findings from caudal epididymal sperm analysis showed significantly high sperm density in the pioglitazone-treated rats at the two doses tested (P < 0.05 compared with diabetic controls). Moreover, pioglitazone at 10 mg/kg improved sperm motility and lowered the percentages of deformed and dead sperm cells in the treated diabetic rats. Haematoxylin and eosin (H&E) sections of the testes showed significantly reduced seminiferous tubule diameter and lumen size, as well as diminished height of the germinal epithelium in the untreated diabetic rats, but not in rats on pioglitazone intervention. Furthermore, Gordon and Sweet section of the testes showed thickened interstitial compartment only in the untreated diabetic group. Meanwhile, interstitial cells of Leydig appeared undisturbed in testicular sections of all the groups, while intratesticular testosterone levels measured by the enzyme immunoassay technique were not significantly different between the treated and control rats (P > 0.05). These findings show that increased sensitization of testicular cells to insulin signalling mediated by the PPAR ? agonist pioglitazone restores testicular histomorphometry and improves semen quality in diabetic rats, despite the weak effect of this drug on blood glucose. Conclusion: This suggests a role for insulin sensitizers and improved insulin signalling in the amelioration of testicular lesions and regulation of spermatogenesis in the diabetic state; and lends support for insulin at promoting testicular functions.