ENVIRONMENTAL POLLUTANT BISPHENOL DISRUPTS THE PROGRAMMING OF SEXUAL BEHAVIOR IN FEMALE RAT OFFSPRING
Authors:   State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Reznikov A.G. , Sachynska O.V. ,   State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Lymareva A.A. ,   State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Polyakova L.I. ,   State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Perchyk I.G. ,   State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Published: March 2023

Bisphenol A (BPA) is a common environmental pollutant and, due to its estrogenic properties, can cause disorders of the reproductive and other physiological systems of the body, especially in males. It is known that in male rats it disrupts the sexual differentiation of the brain (SDB) of the fetus in utero. Studies of the effects of perinatal exposure of fetuses and newborn females through the mother’s body under the conditions of long-term administration of BPA during pregnancy and lactation did not reveal significant changes in SDB. Identification of long-term endocrine, neuromorphological, and behavioral consequences of exposure of female rat fetuses to a low dose of BPA administered to mothers during the last week of pregnancy, which corresponds to the temporal period of SDB, was the aim of this study. Rats were orally administered BPA suspended in Dorfman gel at a daily dose of 25 μg/kg b.w., which is 200 times less than the NOAEL (no observed adverse effect level) for rats, via a gavage, or, as a positive control, estradiol diacetate (E2D) subcutaneously at a dose of 10 μg/kg b.w., during 15-21 days of pregnancy. Control animals received gel without BPA. The levels of estradiol, testosterone, and corticosterone in blood plasma, the response of the hypothalamic-pituitary-adrenal (HPA) axis to acute immobilization stress, sexual behavior, and the histological structure and karyometric parameters of neurocytes of the medial-preoptic nuclei (MPN) of the hypothalamus were studied in adult female offspring. Prenatal exposure to BPA or E2D decreased the concentration of estradiol in the blood plasma, while the levels of testosterone and corticosterone remained normal. In the females of the BPA and E2D groups, a masculinization of sexual behavior (mounting to a receptive female, approaching her, etc.) was observed, which, according to the number of lordosis reactions in the presence of a sexually experienced male, not accompanied by her defeminization. Changes in the morphology of the MPN, which belongs to the sex-dimorphic area of the brain, conformed to the masculinization of female sexual behavior due to prenatal exposure to a low dose of BPA. Karyometry of neurocytes of the hypothalamic MPN of rats revealed no difference between the control and the BPA group. The response of the HPA axis to immobilization stress did not change in both experimental groups. It is found for the first time that maternal exposure of in utero female rat fetuses to an ultra-low relative to the NOAEL dose of BPA during the last gestational week, which corresponds to the critical period of SDB impairs programming of sexual behavior in the direction of its masculinization and causes hypoestrogenemia at adulthood. Disorders of sexual behavior conformed to morphological changes of the hypothalamic MPN. The unidirectionality of functional disorders induced by prenatal exposure to BPA and the reference estrogenic drug E2D indicates that they are caused by the estrogenic properties of both substances.