ENVIRONMENTAL POLLUTANT BISPHENOL DISRUPTS THE PROGRAMMING OF SEXUAL BEHAVIOR IN FEMALE RAT OFFSPRING
A.G. Reznikov, O.V. Sachynska, A.A. Lymareva, L.I. Polyakova, I.G. Perchyk
State Institution V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz69.01.003

Abstract
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.
Keywords:
bisphenol A; prenatal action; sexual behavior; testosterone; estradiol; corticosterone; stress; females; rats.
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