Influence of tamoxifen in utero and lactation exposure: repercussion on reproductive parameters in adulthood in male rats

Abstract

Estradiol is known to be crucial in the process of hypothalamic sexual differentiation, promoting the masculinization of the male hypothalamus. Tamoxifen, a selective non-steroidal estrogen receptor modulator, is used as adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer. Since many breast cancer patients are in reproductive age, pregnancy is delayed until the end of the treatment due to the drug's potential teratogenic effect. However, information on the risk of tamoxifen use in pregnancy is still scarce, and further studies are needed. As tamoxifen has anti-estrogenic action, this study aims to evaluate the effects of perinatal tamoxifen exposure on reproductive parameters in male rats. Therefore, pregnant rats will be exposed to three doses of tamoxifen (0.12; 0.6; 3 µg / kg) between the last pregnancy week (gestational day 15-21) and the end of lactation (postnatal day 20) by gavage. After birth, male pups will be evaluated by 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 for reproductive organ weights, sperm count, sperm morphology and motility, hormone dosage, histopathological analysis of the testis and epididymis. (AU)