P06-15 Exposure to a complex and human-relevant mixture of eight environmental toxicants during folliculogenesis alters ovarian follicular populations in the young adult female rabbit

International audienc

Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle- Aged Men

Abstract Background: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease

Membrane expression of the estrogen receptor ERα is required for intercellular communications in the mammary epithelium.

17β-Estradiol induces the postnatal development of mammary gland and influences breast carcinogenesis by binding to the estrogen receptor ERα. ERα acts as a transcription factor but also elicits rapid signaling through a fraction of ERα expressed at the membrane. Here, we have used the C451A-ERα mouse model mutated for the palmitoylation site to understand how ERα membrane signaling affects mammary gland development. Although the overall structure of physiological mammary gland development is slightly affected, both epithelial fragments and basal cells isolated from C451A-ERα mammary glands failed to grow when engrafted into cleared wild-type fat pads, even in pregnant hosts. Similarly, basal cells purified from hormone-stimulated ovariectomized C451A-ERα mice did not produce normal outgrowths. Ex vivo, C451A-ERα basal cells displayed reduced matrix degradation capacities, suggesting altered migration properties. More importantly, C451A-ERα basal cells recovered in vivo repopulating ability when co-transplanted with wild-type luminal cells and specifically with ERα-positive luminal cells. Transcriptional profiling identified crucial paracrine luminal-to-basal signals. Altogether, our findings uncover an important role for membrane ERα expression in promoting intercellular communications that are essential for mammary gland development

Supplementary Material for: Persistent organic pollutant exposure and thyroid function among 12-year-old children

Introduction Polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs) and per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants (POPs) having numerous toxicological properties, including thyroid endocrine disruption. Our aim was to assess the impact of POPs on thyroid hormones among 12-years children, while taking puberty into consideration Methods Exposure to 7 PCBs, 4 OCPs and 6 PFASs (in µg/L), and free triiodothyronine (fT3, pg/mL), free thyroxine (fT4, ng/dL) and thyroid-stimulating hormones (TSH, mIU/L) were assessed through blood-serum measurements at age 12 in 249 boys and 227 girls of the PELAGIE mother-child cohort (France). Pubertal status was clinically rated using the Tanner stages. For each POP, associations were estimated using linear regression, adjusted for potential confounders. Results Among boys, hexachlorobenzene and perfluorodecanoic acid were associated with decreased fT3 (log-scale; β (95% Confidence Interval) =-0.07 (-0.12,-0.02) and β=-0.03 (-0.06,-0.00) respectively). Intermediate levels of perfluorohexanesulfonic acid (PFHxS) and PCB180 were associated, respectively, with increased and decreased fT4. After stratification on pubertal status, PCBs and OCPs were associated with decreased TSH only in the more advanced Tanner stages (3, 4 and 5) and with decreased fT3 among early Tanner stages (1-2). Among girls, PFHxS was associated with decreased TSH (log-scale; β=-0.15 (-0.29,-0.00)), and perfluorooctanoic acid was associated with decreased fT3 (β2nd_tercile=-0.06 (-0.10,-0.03) and β3rd_tercile=-0.04 (-0.08,-0.00), vs 1st tercile). Discussion / Conclusion This cross-sectional study highlights associations between some POPs and thyroid function disruption, which appears consistent with the literature. Considering that the associations were sex-specific and moderated by pubertal status in boys, complex endocrine interactions are likely involved