Effects of chronic administration of a heme oxygenase substrate or inhibitor on progression of the estrous cycle, pregnancy and lactation of Sprague-Dawley rats

Abstract

The purpose of this study was to investigate whether a heme oxygenase substrate (hemin) or an inhibitor (chromium mesoporphyrin IX; CrMP) had any effect on the normal course of the estrous cycle, pregnancy, parturition or lactation in rats. The hypothesis was that these agents, acting on HO to increase or decrease endogenous production of carbon monoxide (CO) respectively, would disrupt these reproductive processes. The results showed that hemin administered s.c. at 30 μmoles/kg for 10 or 11 days, did not markedly influence the estrous cycle; whereas CrMP blocked the estrous cycle in a dose dependant fashion. At 2 and 4 μmoles/kg for 11 days CrMP significantly reduced the occurrence of estrus phase of the estrous cycle and the effect continued after the treatments were discontinued, while a dose of 1 μmole/kg produced no significant effects. CrMP, administered at 4 μmoles/kg during days 5-14 of pregnancy, led to massive fetal resorption with no live births from 14 successfully mated rats. Administration of hemin at 30 μmoles/kg for 10 days during lactation did not have any effect on milk production, whereas administration of CrMP at 4 μmoles/kg significantly decreased lactational performance which was attributed to milk production and not to suckling intensity of the pups. From these observations we conclude that heme oxygenase, and presumably endogenous CO, play positive roles in female reproductive processes and lactation in the rat.