Prostaglandins, Masculinization and Its Disorders: Effects of Fetal Exposure of the Rat to the Cyclooxygenase Inhibitor- IndomethacinReport as inadecuate




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Recent studies have established that masculinization of the male reproductive tract is programmed by androgens in a critical fetal ‘masculinization programming window’ MPW. What is peculiar to androgen action during this period is, however, unknown. Studies from 20 years ago in mice implicated prostaglandin PG-mediation of androgen-induced masculinization, but this has never been followed up. We therefore investigated if PGs might mediate androgen effects in the MPW by exposing pregnant rats to indomethacin which blocks PG production by inhibiting cyclooxygenase activity during this period and then examining if androgen production or action masculinization was affected.Pregnant rats were treated with indomethacin 0.8 mg-kg-day; e15.5–e18.5 to encompass the MPW. Indomethacin exposure decreased fetal bodyweight e21.5, testis weight e21.5 and testicular PGE2 e17.5, e21.5, but had no effect on intratesticular testosterone ITT; e17.5 or anogenital index AGI; e21.5. Postnatally, AGI, testis weight and blood testosterone were unaffected by indomethacin exposure and no cryptorchidism or hypospadias occurred. Penis length was normal in indomethacin-exposed animals at Pnd25 but was reduced by 26% p<0.001 in adulthood, an effect that is unexplained.Our results demonstrate that indomethacin can effectively decrease intra-testicular PGE2 level. However, the resulting male phenotype does not support a role for PGs in mediating androgen-induced masculinization during the MPW in rats. The contrast with previous mouse studies is unexplained but may reflect a species difference.



Author: Afshan Dean, William Mungall, Chris McKinnell, Richard M. Sharpe

Source: http://plos.srce.hr/



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