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Polychlorinated biphenyls are ubiquitous environmental contaminants linkedc with peripheral immune and neural dysfunction. Neuroimmune signaling is critical to brain development and later health; however, effects of PCBs on neuroimmune processes are largely undescribed. This study extends our previous work in neonatal or adolescent rats by investigating longer-term effects of perinatal PCB exposure on later neuroimmune responses to an inflammatory challenge in adulthood. Male and female Sprague-Dawley rats were exposed to a low-dose, environmentally relevant, mixture of PCBs (Aroclors 1242, 1248, and 1254, 1:1:1, 20 μg / kg dam BW per gestational day) or oil control during gestation and via lactation. Upon reaching adulthood, rats were given a mild inflammatory challenge with lipopolysaccharide (LPS, 50 μg / kg BW, ip) or saline control and then euthanized 3 hours later for gene expression analysis or 24 hours later for immunohistochemical labeling of Iba1+ microglia. PCB exposure did not alter gene expression or microglial morphology independently, but instead interacted with the LPS challenge in brain region- and sex-specific ways. In the female hypothalamus, PCB exposure blunted LPS responses of neuroimmune and neuromodulatory genes without changing microglial morphology. In the female prefrontal cortex, PCBs shifted Iba1+ cells from reactive to hyperramified morphology in response to LPS. Conversely, in the male hypothalamus, PCBs shifted cell phenotypes from hyperramified to reactive morphologies in response to LPS. The results highlight the potential for long-lasting effects of environmental contaminants that are differentially revealed over a lifetime, sometimes only after a secondary challenge. These neuroimmune endpoints are possible mechanisms for PCB effects on a range of neural dysfunction in adulthood, including mental health and neurodegenerative disorders. The findings suggest possible interactions with other environmental challenges that also influence neuroimmune systems., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Margaret Bell reports financial support was provided by National Institute of Environmental Health Sciences. Andrea Gore reports financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study examined the long-term effects of suppressing puberty with a GnRH agonist on reproductive physiology and behavior in female rats. We have recently reported that administration of the GnRH agonist leuprolide acetate (25 µg/kg) daily between postnatal day (PD) 25-50 delayed puberty and disrupted the development of copulatory behavior and sexual motivation in male rats. However, pilot data from our lab suggest that this low dose of leuprolide acetate (25 µg/kg) was not high enough to significantly delay puberty in female rats. Therefore, we injected female Long-Evans rats with leuprolide acetate at a higher dose (50 µg/kg) or 0.9% sterile saline, daily , starting on PD 25 and ending on PD 50. Vaginal opening was monitored daily starting on PD 30 for signs of pubertal onset and first estrous cycle. In addition, we measured estrous cyclicity starting approximately 2 weeks after the last injection of leuprolide (∼PD 64). Immediately after monitoring estrous cyclicity, the female rats were mated on their first day in behavioral estrus using the partner-preference paradigm, with and without physical contact (PD 95-110). We found that this dose of leuprolide (50 µg/kg) significantly delayed puberty; however, neither estrous cyclicity nor sexual motivation was significantly affected by periadolescent exposure to leuprolide. Together with our findings in male rats, these results add to our understanding of the developmental effects of chemically suppressing puberty in rats., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Women are nearly twice as likely to develop mood disorders compared with men, and incidence is greatest during reproductive transitions, including pregnancy and postpartum. Because these periods are characterized by dramatic hormonal and physiologic changes, there is heightened susceptibility to external factors, such as exposure to environmental toxicants, which may play a role in maternal psychopathology. The purpose of this scoping review was to provide an overview of studies conducted in humans and animal models on the effects of nonoccupational exposure to environmental chemicals on maternal psychopathology during the perinatal period. The largest number of studies examined exposure to environmental tobacco smoke and antenatal depression and showed consistently positive findings, although more prospective studies using biomarkers for exposure assessment are needed. The few studies examining persistent organic pollutants such as polybrominated diphenyl ethers and perinatal depression were consistent in showing associations with increased depressive symptoms. Results were mixed for exposure to heavy metals and non-persistent chemicals, but a strong literature in animal models supported an association between bisphenols and phthalates and reduced maternal behavior and care of pups after parturition. Biological mechanisms may include endocrine disruption, neurotransmitter system impairment, alterations in gene expression, and immune activation and inflammation. Additional longitudinal studies that include biospecimen collection are essential to furthering the understanding of how environmental toxicants during pregnancy may affect perinatal psychopathology and the underlying mechanisms of action. Future work should also leverage the parallels between animal and human maternal behavior, thereby highlighting the opportunity for multidisciplinary work in this avenue., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Endocrine-disrupting chemical (EDC) exposures to the fetus have long-lasting effects on health and disease in adulthood. Such EDC exposure to the F1 fetuses also reaches the germ cells that become the F2 generation. Previously, we demonstrated that adult social and communicative behaviors such as ultrasonic vocalizations and mating behaviors were altered by EDCs in F2 rats, especially males. In the current study, we used the brains of these F2 males to ascertain the underlying molecular changes in the hypothalamus related to these behavioral outcomes. Their progenitors were Sprague-Dawley rat dams, treated on pregnancy days 8 to 18 with one of three treatments: a polychlorinated biphenyl (PCB) mixture, Aroclor 1221, selected because it is weakly estrogenic; the anti-androgenic fungicide vinclozolin (VIN); or the vehicle, 6% dimethylsulfoxide in sesame oil (VEH). In adulthood, F1 male and female offspring were bred with untreated partners to generate paternal or maternal lineages of the F2 offspring, the subjects of molecular work. Quantitative real-time PCR was conducted in the medial preoptic area (POA) and the ventromedial nucleus (VMN) of the hypothalamus, selected for their roles in social and sexual behaviors. Of the genes assessed, steroid hormone receptors (estrogen receptor α, androgen receptor, progesterone receptor) but not dopamine receptors 1 and 2 or DNA methyltransferase 3a expression were altered, particularly in the VIN males. Several significant correlations between behavior and gene expression were also detected. These results suggest that preconceptional exposure of male rats to EDCs at the germ cell stage alters the neuromolecular phenotype in adulthood in a lineage-dependent manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Test groups consisting of three males and one female were adapted to home areas within a 244 X 122 cm enclosure for a 4-day period. Subsequently, agonistic interactions and patterns of scent marking were recorded daily for 30 min over the duration of the female's 4-day estrous cycle. Alpha males flank marked significantly more than the two subordinates. The former accounted for over 95% of flank gland marking by males on the two days prior to the female's period of sexual receptivity. The female showed increased frequencies of both flank gland and vaginal marking over the three nonreceptive days of the cycle with the highest frequency of marking occurring 24 hr prior to sexual receptivity. During the two days prior to receptivity, the female both vaginal marked and flank marked significantly more in and about the home area of the alpha male. We conclude that the female hamster shows mate choice prior to the onset of sexual receptivity and that both vaginal marks and flank marks are employed to facilitate mating with the alpha male.