Genital system development and reproductive function of female offspring of rats exposed to cisplatin during peri-puberty.

Abstract

Cisplatin is a drug widely used in chemotherapy against several types of human malignant tumors such as ovarian cancer, head and neck, bladder, lung, and particularly, testicular cancer, one of the tumor that most affect men in reproductive age. Its mechanism of action include induction of cell apoptosis, however, can also cause some adverse effects on reproduction, for example, DNA damage in germ cells, resulting in impaired spermatogenesis. There are several studies that describe the adverse effects of cisplatin on the male reproductive system, but there are few that report the association between cisplatin and the development of female reproductive system of the offspring of rats exposed to the drug. Thus, this study aims to investigate the possible adverse effects on reproductive parameters of female offspring of rats exposed to 1 mg / kg / day cisplatin for 3 weeks, during peri-puberty. For this, the following parameters will be evaluated: fetal ovarian histology, measurement of anogenital distance, number of areolas / nipples, age of vaginal opening and first estrus (indicative of puberty installation), weight and histological evaluation of the reproductive organs (uterus and ovaries), regularity of the estrous cycle,sexual behavior, fertility, hormonal levels and immunohistochemical analysis of androgen and estrogen receptors in uterine tissue. The goal of this proposal is to contribute to the updating of scientific knowledge about the possible adverse effects of the drug on the development and female reproductive function, through the dissemination of results through publications in international and indexed impact journals, as well as communications at scientific meetings in the area, besides the preparation of qualified human resources in Biology and Toxicology of Reproduction.