Targeting Heme Oxygenase-1 in Hypothyroidism Induced Reproductive Dysfunction in Adult Male Rats

Abstract
Background: Hypothyroidism can impair reproductive function leading to infertility.
Aim of the Study: The present study was designed to investigate the possible modulating effect of Heme Oxygenase-1 (HO-1) induction on hypothyroidism-induced reproductive dysfunction in rats.
Material and Methods: Rats were categorized into four groups, 10 rats each. Group I was control, group II (PTU): Received oral 0.05% propyl-thiouracil (PTU) for 8 weeks, group III (PTU + hemin ) received co treatment of oral PTU and hemin (30μmol/kg) by i.p. injections three times per week for 8 weeks and group IV, co administered with oral PTU and zinc protoporphyrin IX (ZnPP) (20μmol/kg) by i.p. injections three times per week for 8 weeks and served as (PTU + Znpp) group. Serum samples were taken to asses thyroid function and serum sex hormones level. Semen samples were taken to detect sperm count and quality, while testicular tissue homoge-nates were used to evaluate oxidative stress markers, ster-oidogenic enzymes and c-Jun NH2-terminal kinases (JNK) activation level together with DNA fragmentation in testicular tissue.
Results: Compared to PTU group, hemin-induced HO-1 up regulation improved the oxidative stress state with enhance-ment of reproductive hormone secretion, which was parallel to abrogation of semen analysis parameters. Further hemin blocked the PTU induced activation of JNK and DNA frag-mentation. On the contrary, inhibition of HO-1 by ZnPP further aggrevated all of the PTU induced changes.
Conclusion: These findings suggested the potential strategy of targeting of HO-1 in improving the hypothyroidism induced reproductive dysfunction.