Male reproductive parameters of rats exposed perinatally to Ibuprofen: morphological, seminal, behavioral and molecular aspects.

Abstract

Prostaglandins (PGE2) are essential in the process of hypothalamic sexual differentiation, promoting the masculinization of hypothalamus in males. The non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (third class of drugs most used by pregnant) act through non-selective inhibition of COX-1 and 2, with the reduction of PGE2. Thus, when used during pregnancy, these substances are able to compromise the hypothalamic differentiation process. This study will evaluate the effects of perinatal exposure to ibuprofen and possible late on reproductive parameters in adult male rats. Pregnant rats will be exposed to three doses of ibuprofen (10; 25; 50 mg/kg) from last week of pregnancy (Gestational days 15-21) to the end of lactation (Postnatal day 20) by gavage. During the treatment, some maternal parameters, such as toxicity signs, behavior, biochemical and hematological analyses will be evaluated. After birth, the male offspring will be assessed using the following parameters: determination of body weight, anogenital distance and ages of preputial separation and testicular descent. In adulthood, these same animals will be investigated regarding weights of reproductive organs, sperm parameters, hormonal dosage, histology of testis, epididymis, pituitary and hypothalamus, sexual behavior, fertility test, volume of the sexually dimorphic nucleus of the preoptic area and quantitative gene expression in real time in hypothalamus genes. (AU)