Recovery of suppressed male reproduction in mice exposed to progesterone during embryonic development by testosterone

The present study aimed to examine whether transplacental exposure to progesterone caused male reproductive abnormalities and whether the changes can be reversed after testosterone administration. Progesterone was injected to mice on day 1, 3, and 7 of pregnancy. The male pups (F1 generation) were allowed to grow for 50 days and assessed for reproductive performance. Gestational exposure to progesterone (7 mg/kg body weight) resulted in significant body weight gain with a decrease in reproductive tissue indices in mice. Total sperm count, viable sperm, and motile sperm decreased in experimental mice. Hypo-osmotic swelling test revealed that experimental mice sperm membrane integrity was severely altered. The activity levels of testicular steroidogenic marker enzymes (hydroxy-delta-5-steroid dehydrogenase, 3 beta-and steroid delta-isomerase cluster (HSD3B) and hydroxysteroid (17-beta) dehydrogenase 1 (HSD17B)) decreased significantly in mice exposed to progesterone during embryonic development when compared with the controls. The levels of serum testosterone decreased with an increase in serum FSH and LH in mice exposed to progesterone during embryonic development. Prenatal exposure to progesterone caused significant reduction in the number of spermatozoa and increase in the lumen of seminiferous tubule. The experimental mice that cohabited with normal females showed fertility reduction. Administration of testosterone (4.16 mg/kg body weight) on postnatal day 20, 30, and 40 to progesterone-exposed prenates resulted in recovery of progesterone-induced suppressed male reproduction. It is suggested that the impairment of male reproduction in mice exposed to progesterone during embryonic development could be mediated through the inhibition of testosterone production. These results also indicate that in utero exposure to progesterone affects male reproduction and that supplementation of testosterone restores the suppressed male reproduction.