The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Abstract

Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the SpragueDawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. KeywordsAroclor 1221; Paced mating; PCB; Female reproductive behavior; Endocrine disruption Polychlorinated biphenyls (PCBs) were used in industry as inflammable coolants and lubricants and as components of paints and plastics. Banned in 1977 in response to dawning public awareness of their estrogenic and potentially toxic effects on humans and wildlife, PCBs continue to leach into soil, air and groundwater via retired industrial equipment, and from old factories and buildings. PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al., 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al., 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al., 1997), alter circulating hormone levels (Desaulniers et al., 1999), change patterns of estrous cyclicity (Meerts et al., 2004;Buitenhuis et al., 2004), disrupt hormone metabolism Kester et al., 2000;Yamane et al., 1975), influence endocrine-related and hypothalamic gene expression ...

Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle

“…Likewise, embryonic exposure to PCB47 or PCB77 reduces adult female-typical sexual behavior in rats [31]. Work from our laboratory showed a diminution in several parameters of feminine sexual behaviors in adult rats that had been exposed prenatally to low doses of A1221 [84]. Moreover, many of these effects exhibited an inverted-U or U-shaped dose-response curve, consistent with effects of both hormones and EDCs on physiological and behavioral endpoints (reviewed in [85]).…”

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

“…Clemens' group has reported consistent deleterious effects of prenatal EDCs on feminine mating behaviors in rats [31,32,160]. My laboratory reported evidence that acute prenatal exposure to low doses of PCBs had permanent consequences on paced mating behavior in adult females [148]. As the ability of a female to control the pace of mating enhances her reproductive success [34] we believe that these data are relevant to non-laboratory animals, including wildlife.…”

“…As the ability of a female to control the pace of mating enhances her reproductive success [34] we believe that these data are relevant to non-laboratory animals, including wildlife. Some of the behavioral effects exerted by prenatal PCBs in our laboratory exhibited an inverted-U or U-shaped dose-response curve [148]. This is important because hormones and EDCs sometimes exert non-linear doseresponse curves due to the range of mechanisms acted upon by these substances, as discussed above and reviewed in Gore et al [63].…”

“…We previously showed that late embryonic (gestational days 16 and/or 18) exposures to the estrogenic PCB mixture, Aroclor 1221 (A1221), decreased expression of ERβ in the AVPV of adult female rats [134], stimulated GnRH mRNA levels in the preoptic area (see Figure 2 and [59]); and altered female paced mating behavior in adulthood [148]. We have recently extended some of our A1221 studies to a second generation.…”

“…We have recently extended some of our A1221 studies to a second generation. In this experiment, pregnant female rats were injected with low doses of A1221 twice during late gestation, on embryonic days 16 and 18 (see [148] for experimental details). Some F1 pups were euthanized on postnatal day (P) 1 for gene expression analysis of the POA.…”