D. Andrew Crain

Female reproductive disorders: the roles of endocrine-disrupting compounds and developmental timing

OBJECTIVE To evaluate the possible role of endocrine-disrupting compounds (EDCs) on female reproductive disorders emphasizing developmental plasticity and the complexity of endocrine-dependent ontogeny of reproductive organs. Declining conception rates and the high incidence of female reproductive disruptions warrant evaluation of the impact of EDCs on female reproductive health. DESIGN Publications related to the contribution of EDCs to disorders of the ovary (aneuploidy, polycystic ovary syndrome, and altered cyclicity), uterus (endometriosis, uterine fibroids, fetal growth restriction, and pregnancy loss), breast (breast cancer, reduced duration of lactation), and pubertal timing were identified, reviewed, and summarized at a workshop. CONCLUSION(S) The data reviewed illustrate that EDCs contribute to numerous human female reproductive disorders and emphasize the sensitivity of early life-stage exposures. Many research gaps are identified that limit full understanding of the contribution of EDCs to female reproductive problems. Moreover, there is an urgent need to reduce the incidence of these reproductive disorders, which can be addressed by correlative studies on early life exposure and adult reproductive dysfunction together with tools to assess the specific exposures and methods to block their effects. This review of the EDC literature as it relates to female health provides an important platform on which womens health can be improved.

Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: The case of Bisphenol A

Background In their safety evaluations of bisphenol A (BPA), the U.S. Food and Drug Administration (FDA) and a counterpart in Europe, the European Food Safety Authority (EFSA), have given special prominence to two industry-funded studies that adhered to standards defined by Good Laboratory Practices (GLP). These same agencies have given much less weight in risk assessments to a large number of independently replicated non-GLP studies conducted with government funding by the leading experts in various fields of science from around the world. Objectives We reviewed differences between industry-funded GLP studies of BPA conducted by commercial laboratories for regulatory purposes and non-GLP studies conducted in academic and government laboratories to identify hazards and molecular mechanisms mediating adverse effects. We examined the methods and results in the GLP studies that were pivotal in the draft decision of the U.S. FDA declaring BPA safe in relation to findings from studies that were competitive for U.S. National Institutes of Health (NIH) funding, peer-reviewed for publication in leading journals, subject to independent replication, but rejected by the U.S. FDA for regulatory purposes. Discussion Although the U.S. FDA and EFSA have deemed two industry-funded GLP studies of BPA to be superior to hundreds of studies funded by the U.S. NIH and NIH counterparts in other countries, the GLP studies on which the agencies based their decisions have serious conceptual and methodologic flaws. In addition, the U.S. FDA and EFSA have mistakenly assumed that GLP yields valid and reliable scientific findings (i.e., “good science”). Their rationale for favoring GLP studies over hundreds of publically funded studies ignores the central factor in determining the reliability and validity of scientific findings, namely, independent replication, and use of the most appropriate and sensitive state-of-the-art assays, neither of which is an expectation of industry-funded GLP research. Conclusions Public health decisions should be based on studies using appropriate protocols with appropriate controls and the most sensitive assays, not GLP. Relevant NIH-funded research using state-of-the-art techniques should play a prominent role in safety evaluations of chemicals.

Environmental endocrine disrupters : an evolutionary perspective

1. The Role of Contaminants as Endocrine Disruptors 2. A background on the evolution of the vetebrate endocrine system 3. The Evolution of Vertebrate Systems Associated with lipid storage and Utilisation, and the Degradation and Excretion Of Toxins 4. Specific Aspects of Endocrine Disrupting contaminants (EDC) 5. The Effects on the Immune System, as Well as the Effects on the Liver and Thyroid

Effect of Acute Stress on Plasma Concentrations of Sex and Stress Hormones in Juvenile Alligators Living in Control and Contaminated Lakes

Environmental contaminants can act as stressors, inducing elevated circulating concentrations of stress hormones such as corticosterone and corticod sol. Development in contaminated eggs has been reported to modify circulating sex steroid hormone concentrations in alligators (Alligator mississippiensis). We ex- amined plasma concentrations of testosterone (T), estradiol-17p (E2), and corticosterone (B) immediately upon and two hours after capture in male and female juvenile alligators living in either contaminated or relatively pristine lake systems. We observed that plasma T concentration was significantly depressed in males from the contaminated lake, whereas plasma E2 showed significant variation between sexes but not between lakes. Initial plasma B concentrations were similar between alligators from both lakes or either sex. Two hours of capture and restraint did not effect plasma T or E2 concentrations but was associated with a dramatic rise in plasma B concentrations. These data suggest that juvenile alligators exposed to contaminants in ovo are apparently unaffected in their rapid glucocorticoid response to acute stress.

Thyroid status in juvenile alligators (Alligator mississippiensis) from contaminated and reference sites on Lake Okeechobee, Florida, USA

Exposure to environmental contaminants has been shown to alter normal thyroid function in various wildlife species, including the American alligator (Alligator mississippiensis). Abnormalities in circulating levels of the thyroid hormone thyroxine (T4) have been reported in juvenile alligators from several contaminated lakes in Florida. To further elucidate these functional thyroid abnormalities, this study examines the structure of thyroids and circulating T4 concentrations from juvenile alligators collected from three sites of varying contamination on Lake Okeechobee, Florida. The following variables were used to characterize thyroid morphology: epithelial cell height, width and area, percent colloid, and follicle area. These variables were compared among study sites and between genders. No difference was detected in epithelial cell height, epithelial cell area, or follicle area among the sites, whereas significant differences in epithelial cell width (p = 0.02) and percent colloid (p = 0.008) were found. Animals from the most contaminated site (Belle Glade) had significantly greater epithelial cell widths and significantly less colloid present in their follicles compared to animals from the reference site (West). Gender did not have a significant interaction with site for any variable measured. Thyroxine (T4) concentrations were elevated in the intermediately contaminated site (Conservation Area 3A) compared to the other sites (p < 0.0001). It is proposed that the disruptions seen in Lake Okeechobee alligators are due to disruptions at both the thyroid and extra-thyroidal tissues.