Johanna R. Rochester

Bisphenol A and human health: A review of the literature

There is growing evidence that bisphenol A (BPA) may adversely affect humans. BPA is an endocrine disruptor that has been shown to be harmful in laboratory animal studies. Until recently, there were relatively few epidemiological studies examining the relationship between BPA and health effects in humans. However, in the last year, the number of these studies has more than doubled. A comprehensive literature search found 91 studies linking BPA to human health; 53 published within the last year. This review outlines this body of literature, showing associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. These studies encompass both prenatal and postnatal exposures, and include several study designs and population types. While it is difficult to make causal links with epidemiological studies, the growing human literature correlating environmental BPA exposure to adverse effects in humans, along with laboratory studies in many species including primates, provides increasing support that environmental BPA exposure can be harmful to humans, especially in regards to behavioral and other effects in children.

Post-hatch oral estrogen exposure reduces oviduct and egg mass and alters nest-building behavior in adult zebra finches (Taeniopygia guttata)

In addition to well recognized effects on the zebra finch song system, we previously showed that post-hatch oral estrogen and xenoestrogen exposure disrupts reproduction by increasing eggshell breakage in females and decreasing fertility in males. Here we show that post-hatch exposure to estradiol benzoate (by oral gavage on days 5 to 11) at a 100 nmol EB per g body mass dose (EB100) also reduces adult oviduct mass. Further, EB100 and doses two orders of magnitude lower (EB10, EB1) reduce egg mass and length. Similar to the induction of song-control nuclei in females, dosing with EB10 and EB100 increased and masculinized another highly differentiated behavior: nest-building. Zebra finches orally exposed as chicks were observed during reproductive trials in communal breeding cages for 4 or 6weeks duration. EB100 males and females and EB10 males showed increased nest-building behaviors. Further, EB10 and EB100 birds had larger nests than canola oil-treated controls, and EB100 birds had faster rates of nest-building than controls, while EB1 birds had significantly slower rates of nest-building than controls. Additionally, EB100 males and females also showed an increased preference for a coarser male-typical nest-building material (jute) over a finer, female-typical material (wool), suggesting a masculinization of nest-building behavior at the higher doses. The change in zebra finch nest-building behavior induced by early EB exposure suggests that nest size and quality, in addition to egg mass and length, may provide new endpoints for assessing avian exposure to xeno- and phyto-estrogens in wild birds.

Dietary red clover (Trifolium pratense) induces oviduct growth and decreases ovary and testes growth in Japanese quail chicks

To determine whether drought-stress alters phytoestrogens in red clover and whether red clover in the diet influences sexual development in Japanese quail, we fed chicks diets containing irrigated or non-irrigated clover. Irrigation altered phytoestrogenic activity of red clover (determined using an in vitro bioassay), with extracts of irrigated clover diet containing more estrogenic activity than extracts of non-irrigated clover diet. Chick growth was negatively correlated with the amount of irrigated or non-irrigated clover in the diet. Dietary red clover also depressed both absolute and relative gonad weights; however, relative oviduct weight was increased by the irrigated diet. Diets did not affect serum vitellogenin. These results reveal a negative influence of drought-stress on phytoestrogenic potency of clover, and that red clover in the diet can inhibit avian growth and development independent of irrigation state. Thus, phytoestrogens may affect reproductive development in wild birds, and environmental stressors may influence levels of phytoestrogens in the field.

Post-hatch oral estrogen in zebra finches (Taeniopygia guttata): Is infertility due to disrupted testes morphology or reduced copulatory behavior?

Previous studies show that post-hatch oral exposure of zebra finches to estradiol benzoate compromises male fertility, but the basis of the infertility is not clear. In this study, zebra finch nestlings were orally dosed with estradiol benzoate (at 1, 10, or 100 nmol/g BW per day, post-hatch days 5 to 11 [EB1, EB10, and EB100, respectively]). EB10 and EB100 males exhibited no significant differences in the frequency of mounting behavior (compared to canola oil [vehicle]-treated controls), when observed for six weeks as adults in communal breeding cages with similarly treated females; EB1 males showed reduced mounting behavior compared to controls (p<0.05). EB- and control-treated adult pairs were subsequently co-housed in a communal breeding trial to determine the extent of parentage outside the established pair-bond. Microsatellite analysis was consistent with EB-treated males having lower success than controls in obtaining paternity outside the established pair-bond. Histological examination of testes revealed dose-related disruption of normal morphology: disrupted basal-to-lumen laminarity of spermatogenesis stages, increased vacuolization within seminiferous tubules, decreased sperm aggregation and decreased spermatid density. Additionally, EB100 and control males were housed individually, implanted with testosterone propionate (TP) and presented with a female 3, 5, 9, and 11 days post-implantation for assessment of male sexual behavior. EB-treated, TP-implanted birds showed a slight decrease in mounting and singing behavior on day 5 after implantation; other male courtship behaviors (display, solicitation) were unaffected. Taken together, these results suggest that infertility in male zebra finches resulting from early oral estrogen exposure is more likely due to disrupted testicular morphology than altered sexual behavior.

Polycyclic aromatic hydrocarbons and female reproductive health: A scoping review

Polycyclic aromatic hydrocarbons (PAHs) are a class of common persistent environmental pollutants found in water, air, soil, and plants and can be released by natural sources. However, the majority of atmospheric PAHs are from vehicular emissions, coal-burning plants, and the production and use of petroleum-derived substances. Exposure to PAHs has been implicated in cancer and other diseases, including reproductive disorders. This scoping review is a preliminary step that explores the utility and feasibility of completing a systematic review evaluating the effect of PAHs on female reproduction. We performed literature searches in PubMed, Web of Science, and Scopus, then screened, identified, and categorized relevant studies. Our results identified fertility and pregnancy/fetal viability as outcomes with sufficient research for systematic review. In addition to presenting the relevant studies, the review identifies data gaps, and provides the groundwork to develop the most appropriate research questions for systematic review.

Potential Developmental and Reproductive Impacts of Triclocarban: A Scoping Review

Triclocarban (TCC) is an antimicrobial agent used in personal care products. Although frequently studied with another antimicrobial, triclosan, it is not as well researched, and there are very few reviews of the biological activity of TCC. TCC has been shown to be a possible endocrine disruptor, acting by enhancing the activity of endogenous hormones. TCC has been banned in the US for certain applications; however, many human populations, in and outside the US, exhibit exposure to TCC. Because of the concern of the health effects of TCC, we conducted a scoping review in order to map the current body of literature on the endocrine, reproductive, and developmental effects of TCC. The aim of this scoping review was to identify possible endpoints for future systematic review and to make recommendations for future research. A search of the literature until August 2017 yielded 32 relevant studies in humans, rodents, fish, invertebrates, and in vitro. Based on the robustness of the literature in all three evidence streams (human, animal, and in vitro), we identified three endpoints for possible systematic review: estrogenic activity, androgenic activity, and offspring growth. In this review, we describe the body of evidence and make recommendations for future research.

Prenatal exposure to bisphenol A and hyperactivity in children: a systematic review and meta-analysis

BACKGROUND Attention-deficit hyperactivity disorder (ADHD) has increased in prevalence in the past decade. Studies attempting to identify a specific genetic component have not been able to account for much of the heritability of ADHD, indicating there may be gene-environment interactions underlying the disorder, including early exposure to environmental chemicals. Based on several relevant studies, we chose to examine bisphenol A (BPA) as a possible contributor to ADHD in humans. BPA is a widespread environmental chemical that has been shown to disrupt neurodevelopment in rodents and humans. OBJECTIVES Using the Office of Health Assessment and Translation (OHAT) framework, a systematic review and meta-analysis was designed to determine the relationship between early life exposure to BPA and hyperactivity, a key diagnostic criterion of ADHD. DATA SOURCES Searches of PubMed, Web of Science, and Toxline were completed for all literature to January 1, 2017. STUDY ELIGIBILITY CRITERIA For inclusion, the studies had to publish original data, be in the English language, include a measure of BPA exposure, and assess if BPA exposure affected hyperactive behaviors in mice, rats or humans. Exposure to BPA had to occur at <3 months of age for humans, up to postnatal day 35 for rats and up to postnatal day 40 for mice. Exposure could occur either gestationally (via maternal exposure) or directly to the offspring. STUDY APPRAISAL AND SYNTHESIS METHODS Studies were evaluated using the OHAT risk of bias tool. The effects in humans were assessed qualitatively. For rodents exposed to 20 μg/kg/day BPA, we evaluated the study findings in a random effects meta-analytical model. RESULTS A review of the literature identified 29 rodent and 3 human studies. A random effects meta-analysis showed significantly increased hyperactivity in male rodents. In humans, early BPA exposure was associated with hyperactivity in boys and girls. LIMITATIONS, CONCLUSIONS, AND IMPLICATIONS OF KEY FINDINGS We concluded that early life BPA exposure is a presumed human hazard for the development of hyperactivity. Possible limitations of this systematic review include deficiencies in author reporting, exclusion of some literature based on language, and insufficient similarity between human studies. SRs that result in hazard-based conclusions are the first step in assessing and mitigating risks. Given the widespread exposure of BPA and increasing diagnoses of ADHD, we recommend immediate actions to complete such risk analyses and take next steps for the protection of human health. In the meantime, precautionary measures should be taken to reduce exposure in pregnant women, infants and children. The present analysis also discusses potential mechanisms by which BPA affects hyperactivity, and the most effective avenues for future research. SYSTEMATIC REVIEW REGISTRATION NUMBER Not available.