Abstract
Endocrine-disrupting chemicals (EDCs) lead to endocrine and neurobehavioral changes, particularly due to developmental exposures during gestation and early life. Moreover, intergenerational and transgenerational phenotypic changes may be induced by germline exposure (F2) and epigenetic germline transmission (F3) generation, respectively. Here, we assessed reproductive and sociosexual behavioral outcomes of prenatal Aroclor 1221 (A1221), a lightly chlorinated mix of PCBs known to have weakly estrogenic mechanisms of action; estradiol benzoate (EB), a positive control; or vehicle (3% DMSO in sesame oil) in F1-, F2-, and F3-generation male and female rats. Treatment with EDCs was given on embryonic day (E) 16 and 18, and F1 offspring monitored for development and adult behavior. F2 offspring were generated by breeding with untreated rats, phenotyping of F2s was performed in adulthood, and the F3 generation were similarly produced and phenotyped. Although no effects of treatment were found on F1 or F3 development and physiology, in the F2 generation, body weight in males and uterine weight in females were increased by A1221. Mating behavior results in F1 and F2 generations showed that F1 A1221 females had a longer latency to lordosis. In males, the F2 generation showed decreased mount frequency in the EB group. In the F3 generation, numbers of ultrasonic vocalizations were decreased by EB in males, and by EB and A1221 when the sexes were combined. Finally, partner preference tests in the F3 generation revealed that naïve females preferred F3-EB over untreated males, and that naïve males preferred untreated over F3-EB or F3-A1221 males. As a whole, these results show that each generation has a unique, sex-specific behavioral phenotype due to direct or ancestral EDC exposure.
Highlights
Endocrine-disrupting chemicals (EDCs) interfere with hormone action within an organism [1,2]
The current study aims to build upon previous studies in the lab that identified transgenerational effects of polychlorinated biphenyls (PCBs) on physiology, behavior, and hypothalamic gene expression throughout development [29,30,34,35]
The current study demonstrates that a transient gestational exposure to estrogenic EDCs can significantly alter behaviorally relevant endpoints for at least three generations
Summary
Endocrine-disrupting chemicals (EDCs) interfere with hormone action within an organism [1,2]. These chemicals, or mixture of chemicals, act upon the neuroendocrine systems that govern physiological processes such as reproduction, immune function, metabolism, and sex-typical behaviors in adulthood. Regarding neuroendocrine functions and hormonedependent behaviors, the focus of this study, exposures to EDCs including bisphenol A (BPA), phthalates, and persistent organic pollutants such as polychlorinated biphenyls (PCBs) induce adverse phenotypic outcomes in animal studies [4,5,6,7,8,9,10,11,12,13,14,15,16,17], and are associated with increased prevalence of neurobehavioral disorders in epidemiological studies in humans [18,19,20,21,22]. More research comparing generational effects is needed to better understand how legacy chemicals that are no longer actively manufactured but are still persistent in the environment, such as PCBs, may lead to heritable effects generations later
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