Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats

Fernández, Marina Olga; Bourguignon, Natalia; Arocena, Paula; Matias, Rosa; Libertun, Carlos; Lux‐Lantos, Victoria

doi:10.1016/j.toxlet.2017.12.029

Cited by 50 publications

(21 citation statements)

References 35 publications

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“…Pregnant female rats exposed to BPA experienced transient hypothyroidism, while their male pups underwent transient hyperthyroidism, followed by hypothyroidism (Xu et al 2007). Infant rats exposed during the neonatal period did not present any alterations, but the adult female animals developed a TH status similar to hypothyroidism, and evidence in a primary pituitary cell line showed that BPA alters TSH release through direct action on the pituitary (Fernandez et al 2018). Studies with pregnant ewes, which have a gestational period more comparable to that of humans, that were exposed to BPA both subcutaneously and by dietary exposure demonstrated lower levels of THs in pregnant females and newborns, and those females showed evidence of a modified deiodination balance (Viguie et al 2013, Guignard et al 2017.…”

Section: Plasticizersmentioning

confidence: 97%

Thyroid function disruptors: from nature to chemicals

Oliveira

Chiamolera

Giannocco

et al. 2019

Journal of Molecular Endocrinology

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The modern concept of thyroid disruptors includes man-made chemicals and bioactive compounds from food that interfere with any aspect of the hypothalamus-pituitary-thyroid axis, thyroid hormone biosynthesis and secretion, blood and transmembrane transport, metabolism and local action of thyroid hormones. This review highlights relevant disruptors that effect populations through their diet: directly from food itself (fish oil and polyunsaturated fatty acids, pepper, coffee, cinnamon and resveratrol/grapes), through vegetable cultivation (pesticides) and from containers for food storage and cooking (bisphenol A, phthalates and polybrominated diphenyl ethers). Due to the vital role of thyroid hormones during every stage of life, we review effects from the gestational period through to adulthood, including evidence from in vitro studies, rodent models, human trials and epidemiological studies.

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Section: Plasticizersmentioning

confidence: 97%

Thyroid function disruptors: from nature to chemicals

Oliveira

Chiamolera

Giannocco

et al. 2019

Journal of Molecular Endocrinology

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“… Author Animal strain Exposure period Route of exposure and dose Analyte Time of assay Sex Finding Zoeller et al [ 206 ] Sprague Dawley (Zivic-Miller) G6-P21 Wafer 0, 1, 10, 50 mg/kg daily Total T 4 P4, P8, P15, P35 No sex differences ↑ total T 4 on P15 only Maternal only Xu et al [ 214 ] Sprague Dawley Nippon Clea G11-P21 Drinking water (in 0.01 % EtOH) Free T 4 P0, P7, P11, P21 No sex differences ↔ T 4 on P0, ↑ T 4 on P7, ↓T 4 on P21. Maternal only 0, 0.1 and 50 mg/L Ahmed et al [ 218 ] Wistar P15- P30 Gavage Free T 4 * P30 Not reported ↓ T 4 on P30 VACSERA Pups 0, 20, 40 μg/kg Fernandez et al [ 219 ] Sprague Dawley P1-P10 Subcutaneous injection Total T 4 P90-120 Females only ↓ T 4 in estrus females IBYME colony …”

Section: R Thomas Zoeller: Effects Of Bpa On the Thyroidmentioning

confidence: 99%

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Heindel

Belcher

Flaws

et al. 2020

Reproductive Toxicology

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Consortium Linking Academic and Regulatory Insights on BPA Toxicity" (CLARITY-BPA) was a comprehensive "industry-standard" Good Laboratory Practice (GLP)-compliant 2-year chronic exposure study of bisphenol A (BPA) toxicity that was supplemented by hypothesis-driven independent investigator-initiated studies. The investigator-initiated studies were focused on integrating disease-associated, molecular, and physiological endpoints previously found by academic scientists into an industry standard guideline-compliant toxicity study. Thus, the goal of this collaboration was to provide a more comprehensive dataset upon which to base safety standards and to determine whether industry-standard tests are as sensitive and predictive as molecular and disease-associated endpoints. The goal of this report is to integrate the findings from the investigator-initiated studies into a comprehensive overview of the observed impacts of BPA across the multiple organs and systems analyzed. For each organ system, we provide the rationale for the study, an overview of methodology, and summarize major findings. We then compare the results of the CLARITY-BPA studies across organ systems with the results of previous peer-reviewed studies from independent labs. Finally, we discuss potential influences that contributed to differences between studies. Developmental exposure to BPA can lead to adverse effects in multiple organs systems, including the brain, prostate gland, urinary tract, ovary, mammary gland, and heart. As published previously, many effects were at the lowest dose tested, 2.5μg/kg /day, and many of the responses were non-monotonic. Because the low dose of BPA affected endpoints in the same animals across organs evaluated in different labs, we conclude that these are biologically-and toxicologically-relevant.

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“…Adewale et al (2009) found that DVO was significantly advanced by neonatal (PND0 to PND3) administration of the low‐dose BPA (50 μg/kg body weight [bw]) but not the high dose of BPA (50 mg/kg bw) compared with the control animals. Females exposed to the medium dose of BPA (6.2–2.5 mg/kg from PND1 to PND10) exhibited the highest TSH levels, whereas the high (62.5–25.0 mg/kg) and low (0.625–0.25 mg/kg) dose treated animals showed slight increases that are not statistically significant (Fernandez et al, 2018). However, the data in this study indicated a linear dose‐response effect of BPA exposure.…”

Section: Discussionmentioning

confidence: 99%

Neonatal exposure to bisphenol A advances pubertal development in female rats

Qiu

Sun

et al. 2020

Molecular Reproduction Devel

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Neonatal exposure to bisphenol A (BPA) is hypothesized to advance pubertal development. However, the effects of neonatal BPA exposure on pubertal development has not been described. In this study, female Sprague-Dawley rats were exposed to 0.05, 0.5, 5, or 10 mg·kg −1 ·day −1 BPA, or corn oil vehicle alone from postnatal day 1 (PND1) to PND10 via subcutaneous injection. We evaluated day of vaginal opening (DVO), ovarian morphology, serum hormone concentrations, and hypothalamic expression of Gnrh1 and Kiss1 in female rats at PND35. DVO was significantly advanced in rats exposed to 5 and 10 mg·kg −1 ·day −1 BPA. Serum hormone concentrations increased as BPA dose increased. Additionally, hypothalamic Gnrh1 and Kiss1 expression were increased with BPA exposure; rats exposed to 10 mg·kg −1 ·day −1 BPA had significantly upregulated hypothalamic Gnrh1 and Kiss1 expressions in terms of both messenger RNA and protein levels. Our results suggest that exposure to a 10 mg·kg −1 ·day −1 dose of BPA might advance pubertal development significantly. In addition, within the range of 0 to 10 mg·kg −1 ·day −1 , neonatal exposure to BPA may affect pubertal development in a dose-dependent manner.

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Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats

Cited by 50 publications

References 35 publications

Thyroid function disruptors: from nature to chemicals

Thyroid function disruptors: from nature to chemicals

Data integration, analysis, and interpretation of eight academic CLARITY-BPA studies

Neonatal exposure to bisphenol A advances pubertal development in female rats

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