Endocrine Disruption of Brain Sexual Differentiation by Developmental PCB Exposure

Abstract

In mammals, sexual differentiation of the hypothalamus occurs during prenatal and early postnatal development due in large part to sex differences in hormones. These early organizational processes are critically important for the attainment and maintenance of adult reproductive functions. We tested the hypothesis that perinatal exposure to polychlorinated biphenyls (PCBs) that disrupt hormonal pathways would perturb reproductive maturation and the sexually dimorphic development of neuroendocrine systems in the preoptic area (POA). Pregnant Sprague-Dawley rats were injected on gestational d 16 and 18 with vehicle (dimethylsulfoxide), Aroclor 1221 (A1221, an estrogenic PCB mix), a reconstituted PCB mixture representing those highest in human body burden (PCBs 138, 153, 180), or estradiol benzoate, an estrogenic control. Male and female pups were monitored for somatic and reproductive development. In adulthood, some rats were perfused and used for immunohistochemistry of estrogen receptor α, kisspeptin, and coexpression of Fos in GnRH neurons. Other rats were used to obtain fresh-frozen POA dissections for use in a PCR-based 48-gene expression array. Pubertal onset was advanced and estrous cyclicity irregular in endocrine-disrupted females. Furthermore, sexual differentiation of female neuroendocrine systems was masculinized/defeminized. Specifically, in the adult female anteroventral periventricular nucleus, estrogen receptor α-cell numbers and kisspeptin fiber density were significantly decreased, as was GnRH-Fos coexpression. PCR analysis identified androgen receptor, IGF-I, N-methyl-d-aspartate receptor subunit NR2b, and TGFβ1 mRNAs as significantly down-regulated in endocrine-disrupted female POAs. These data suggest that developmental PCBs profoundly impair the sexual differentiation of the female hypothalamus.

Neuronal basis of reproductive dysfunctions associated with diet and alcohol: From the womb to adulthood

“…In HFD-exposed obese females, the earlier accelerated GnRH pulse generator frequency and advanced puberty might be associated with premature up-regulation of kisspeptin and NKB signaling in the hypothalamus [131]. Similarly, exposure during pregnancy to polychlorinated biphenyls (PCBs) -chemicals found in polycarbonate plastics and other materials [133] -led to advanced pubertal onset and abnormal estrous cyclicity in female offspring [134].…”

Endocrine Disruptors Are a Novel Direction of Endocrinologic Scientific Investigation

“…Они нару-шают функциональную деятельность щитовидной железы, снижая продукцию тиреоидных гормонов, печени и про-цессы обмена веществ, наиболее выраженные в прена-тальном периоде развития особи с последующим разви-тием детского ожирения и риском возникновения сахарного диабета [31,32]. Воздействие ПХБ в пренатальном периоде развития организма приводит к нарушениям половой диф-ференцировки гипоталамуса [33]. Однако механизмы эндо-кринных нарушений остаются еще малоизученными.…”

Daily intake of anthropogenic pollutants through yogurt consumption in the Spanish population

“…Among them persistent organic pollutants (POPs) are organic compounds characterized by their stable structures and lipophilicity that are resistant to the degradation in the environment and biota. Over the last 30 years a number of these substances have been highlighted as a cause for concern (Dorgan et al 1999;Ribas-Fito et al 2001;Samanta et al 2002;Knerr & Schrenk 2006;Valerón et al 2009;Casals-Casas & Desvergne 2011;Dickerson et al 2011;Boada et al 2012 ) and have been the subject of extensive study and international regulation. Among them the halogenated hydrocarbons such as organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) are especially relevant.…”