Endocrine and behavioral effects in male rats after birth with their pregnant mother taking ibuprofen

Abstract

Ibuprofen, a non-selective inhibitor of cyclooxygenase, is one of the most used non-steroidal anti- inflammatory drugs (NSAID) and pain relievers. Its effect on developing fetal neuroendocrine system when taken by a pregnant mother does not well established. The aim of this study was to evaluate the long-term consequences of the administration of ibuprofen to pregnant rats with regard to hormonal profile and sexual differentiation of the brain in male offspring. Pregnant rats were given ibuprofen per os in a dose of 30 mg/kg bw twice a day during days 15-21 of gestation. On the 2 and 10 postnatal days (PND), anogenital distance (AGD) was measured in male pups. In adulthood, sexual behavior, hormone levels, and hypothalamic-pituitary-adrenal axis (HPAA) response to acute immobilization stress were studied. Prenatal ibuprofen increased AGD on PND 2 and caused incomplete masculinization of copulative behavior in adult offspring. Significant increases in the latent periods of the first mount, the first intromission, and a decrease in the number of intromissions were observed. Basal blood plasma levels of testosterone, estradiol, and corticosterone, as well as HPAA response to immobilization stress, did not change. Orchidectomized and primed with estradiol and progesterone males did not exhibit lordosis response to the presence of a sexually experienced male. Conclusion: Administration of ibuprofen to female Wistar rats during the last week of gestation disrupts partially neuroendocrine programming of male-type copulative behavior in male offspring with no changes in female-type sexual behavior and HPAA function. It is hypothesized that incomplete masculinization of the developing fetal brain with ibuprofen is due to two co-operative mechanisms: inhibition of synthesis of testosterone in the fetal gonads and prostaglandin E2 in the preoptic area of the hypothalamus.