SAT424 Neuroendocrine And Developmental Impacts Of Early Exposure To Estrogenic Endocrine Disruptors

Abstract

Abstract Disclosure: M. Streifer: None. S. Mendez: None. R. Raval: None. L. Thompson: None. A.C. Gore: None. Polychlorinated biphenyls (PCBs) are a class of endocrine disrupting chemical (EDC), exposure to which during early development can result in a variety of neuroendocrine and reproductive abnormalities. Hypothalamic kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) and KNDy (Kisspeptin-Neurokinin B-Dynorphin expressing) neurons in the arcuate nucleus (ARC) are involved in reproductive development, maturation, and success; dysfunctions in kisspeptin signaling can lead to hypogonadotropic hypogonadism and sub- or infertility. KNDy and kisspeptin neurons develop under the influence of gonadal hormones, notably estradiol, and are vulnerable to early exposure to estrogenic EDCs. In this experiment male and female rats were perinatally exposed to the weakly estrogenic PCB mixture Aroclor 1221 (A1221) to determine if and how altered kisspeptin signaling in the ARC and AVPV affects reproductive development. Using RNAscope, a novel in situ hybridization technique, we are exploring if changes in the number of KNDy and kisspeptin neurons or RNA expression of kisspeptin and regulatory peptides neurokinin B and dynorphin are potential mechanisms of the increased incidence of reproductive disorders associated with estrogenic PCB exposure. A1221 exposure did not alter the number of kisspeptin-expressing neurons in the AVPV, though quantification of RNA expression and analysis in the ARC are still ongoing. Serum LH, FSH, estradiol, and testosterone were measured as they are involved in the kisspeptin signaling pathway. In A1221 exposed females, serum LH and FSH were decreased, and estradiol was increased in early life (postnatal day 8). A1221 exposed males had decreased serum LH at a prepubertal time point (postnatal day 30), but FSH and testosterone were unaffected by treatment. Developmental markers that could be indicative of dysfunctions in kisspeptin and KNDy neuron function were monitored. A1221 exposure did not cause any obvious abnormal developmental delays in males or females. Moving forward, we plan on further exploring the effects of developmental A1221 exposure in the AVPV and ARC through gene expression profiling. Presentation: Saturday, June 17, 2023