Anxiety-like behaviors in adulthood are altered in male but not female rats exposed to low dosages of polychlorinated biphenyls in utero

Abstract

Exposure to polychlorinated biphenyls (PCBs), a class of endocrine-disrupting chemicals, can result in altered reproductive behavior in adulthood, especially when exposure occurs during critical periods of brain sexual differentiation in the fetus. Whether PCBs alter other sexually dimorphic behaviors such as those involved in anxiety is poorly understood. To address this, pregnant rat dams were injected twice, on gestational days 16 and 18, with the weakly estrogenic PCB mixture Aroclor 1221 (A1221) at one of two low dosages (0.5 mg/kg or 1.0 mg/kg, hereafter 1.0 and 0.5), estradiol benzoate (EB; 50 μg/kg) as a positive estrogenic control, or the vehicle (3% DMSO in sesame oil). We also conducted a comprehensive assessment of developmental milestones of the F1 male and female offspring. There were no effects of treatment on sex ratio at birth and age at eye opening. Puberty, assessed by vaginal opening in females and preputial separation in males, was not affected in females but was advanced in males treated with A1221 (1.0). Males and females treated with A1221 (both dosages) were heavier in early adulthood relative to controls. The earliest manifestation of this effect developed in males prior to puberty and in females slightly later, during puberty. Anxiety-like behaviors were tested using the light:dark box and elevated plus maze tests in adulthood. In females, anxiety behaviors were unaffected by treatment. Males treated with A1221 (1.0) showed reduced indices of anxiety and increased activity in the light:dark box but not the elevated plus maze. EB failed to replicate the phenotype produced by A1221 for any of the developmental and behavioral endpoints. Collectively, these results indicate that PCBs increase body weight in both sexes, but their effects on anxiety-like behaviors are specific to males. Furthermore, differences between the results of A1221 and EB suggest that the PCBs are likely acting through mechanisms distinct from their estrogenic activity.

Passing experiences on to future generations: endocrine disruptors and transgenerational inheritance of epimutations in brain and sperm

“…Fourth, our lab has previously utilized a very short exposure window for A1221 (E16 and E18 only) to determine its effects during the beginning of the critical window of sexual differentiation [37,38]. Here, we extended the exposure window (E8-18) to encompass the period of germline erasure and reestablishment in fetal males (E8-14, e.g., [21]).…”

Aging and estradiol effects on gene expression in the medial preoptic area, bed nucleus of the stria terminalis, and posterodorsal medial amygdala of male rats

“…Eta-squared represents the proportion of variance accounted for by the factor that is tested. An η 2 greater than 0.06 is considered medium and an η 2 greater than 0.14 is considered large (Gillette et al, 2016). …”

Sexually Dimorphic Effects of Early-Life Exposures to Endocrine Disruptors: Sex-Specific Epigenetic Reprogramming as a Potential Mechanism

“…The influence of heavy metals, including lead (Pb) on the endocrine system, is also an emerging area of research in humans and animal models [21]. Hormone signaling is sexually dimorphic in nature, and thus EDCs that disrupt hormonal pathways may elicit sex-specific effects, including altered metabolism, behavior, and cognition [17, 22–24]. …”