Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels.

Rubin, Beverly S.; Murray, Mary K.; Damassa, David A.; King, Joan C.; Soto, Ana M.

doi:10.1289/ehp.01109675

Cited by 525 publications

(251 citation statements)

References 53 publications

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“…The perinatal low-dose BPA exposure had no obvious effect on the reproductive physiology of their offspring, as deduced by observations of anogenital distance, puberty onset, ovarian histology and vaginal smears, in agreement with the literature regarding low-dose exposures (Ashby 2001, Rubin et al 2001, Tinwell et al 2002, Yoshida et al 2004, Patisaul & Polston 2008, Poimenova et al 2010. However, the reduced male:female offspring ratio in BPA-treated dams, though not statistically significant in this study, may imply a male embryo selective vulnerability in utero that worth further investigation.…”

Section: Reproductive Physiologysupporting

confidence: 90%

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

Panagiotidou¹,

Zerva²,

Mitsiou³

et al. 2013

Journal of Endocrinology

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Bisphenol A (BPA) is an estrogen-mimicking endocrine disruptor. Early-life exposures to low doses of BPA exert long-lasting effects on animals' reproductive and brain physiology. However, little is known about the effects of BPA on the stress-response system. Given the interaction of sex and stress hormones, we examined the effect of a low perinatal BPA exposure on the function of the hypothalamic-pituitary-adrenal (HPA) axis at rest and upon application of acute stress. Throughout pregnancy and lactation rats received daily 40 mg BPA/kg body weight orally via cornflakes. We studied the effect of this low but chronic exposure to BPA in the male and female offspring at puberty. BPA exposure led to abnormal adrenal histology including reduced zona reticularis especially in male offspring, hyperplasia of zona fasciculata in both sexes, and increased adrenal weight in female offspring. BPA-treated females had increased basal corticosterone and reduced hypothalamic glucocorticoid receptors (GR) levels. Stressed BPA-exposed females exhibited anxiety-like behavioral coping, a less rigorous corticosterone response, and did not downregulate GR in the hypothalamus, compared with control females. BPA-exposed males exhibited a heightened corticosterone stress response compared with females; they also displayed increased pro-opiomelanocortin mRNA levels and retained the prestress levels of pituitary corticotropin-releasing hormone-receptor 1, compared with control males. We found that perinatal chronic exposure to a low dose of BPA perturbs the basal and stress-induced activity of the HPA axis in a sexually dimorphic manner at adolescence. Exposure to BPA might contribute to increased susceptibility to stress-related disorders in later life.

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Section: Reproductive Physiologysupporting

confidence: 90%

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

Panagiotidou¹,

Zerva²,

Mitsiou³

et al. 2013

Journal of Endocrinology

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“…However, irregular estrous cyclicity could not be detected in our BPA study in which animals were exposed to 3000 ppm (corresponding to 231.8 mg/kg per day during the gestational period and 384.4 mg/kg per day during the lactation period). A similar lack of effects on estrous cyclicity was reported by others using rats or mice (Kwon et al 2000;Suzuki et al 2002) at doses much higher than those of Rubin et al (2001). Differences in the exposure time-windows or exposure protocols do not appear to be responsible for the discrepancy, because Kwon and colleagues selected a wide time window for exposure similar to that of Rubin and coworkers, and Suzuki and colleagues chose the more potent subcutaneous injection route.…”

Section: Discussionmentioning

confidence: 55%

“…Although as an estrogenic reference drug EE exposure at 0.5 ppm exerted obvious endocrine effects on offspring, neither BPA nor NP, even at doses causing maternal toxicity, did not affect development of the endocrine/reproductive systems. Rubin et al (2001) reported that maternal perinatal exposure to BPA induced irregular estrous cyclicity in rats at a dose level corresponding to 1.2 mg/kg per day in the drinking water from GD 6 to PND 22. However, irregular estrous cyclicity could not be detected in our BPA study in which animals were exposed to 3000 ppm (corresponding to 231.8 mg/kg per day during the gestational period and 384.4 mg/kg per day during the lactation period).…”

Section: Discussionmentioning

confidence: 99%

Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life

Takagi

Shibutani

Masutomi

et al. 2004

Archives of Toxicology

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Two potential endocrine-disrupting chemicals, bisphenol A (BPA) and nonylphenol (NP), were assessed for their long-lasting effects on endocrine/reproductive systems following transplacental and lactational exposure to rat offspring during a time-window that included the critical period for brain sexual differentiation. Each chemical was mixed with diet at concentrations of 60, 600 and 3000 ppm and was provided to maternal Sprague-Dawley rats from gestational day (GD) 15 to postnatal day (PND) 10. Ethinylestradiol (EE) at 0.5 ppm was used as an estrogenic reference drug. During pregnancy and lactation, including the exposure period, a soy-free rodent diet was provided to eliminate possible modification of the study results by plant-derived phytoestrogens. Effects on endocrine/reproductive systems were evaluated by examining the anogenital distance, organ weights before puberty, onset of puberty, estrous cyclicity, and organ weights and histopathology of adult endocrine organs (at 11 weeks of age), as well as the volume of the sexually dimorphic nucleus of preoptic area. Both NP and BPA, at high doses, caused decreases in maternal body weights and retardation of offspring growth, but neither affected any of the endocrine/reproductive endpoints of offspring, whereas EE induced irreversible changes in estrous cyclicity and histopathology of ovaries and uterus of adult females. The results indicated that maternal dietary exposure to NP or BPA at concentrations up to 3000 ppm from GD 15 through PND 10 do not exert any apparent adverse effects on the endocrine/reproductive systems of offspring.

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“…Several studies in rodent models have reported that perinatal exposure to BPA increases the body weight of offspring at 6 months of age (Alonso-Magdalena et al 2010) and in adulthood (Somm et al 2009) as well as in the neonatal period (Howdeshell et al 1999, Rubin et al 2001, Rubin & Soto 2009). However, Ryan et al (2010) reported a contrary result that oral exposure to BPA during the perinatal period did not induce glucose intolerance later in life in CD-1 mice.…”

mentioning

confidence: 99%

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

Moon¹,

Jeong²,

Oh³

et al. 2015

Journal of Endocrinology

103

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Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4-to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 mg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9G16.8 vs 97.9G18.2 mM/min, PZ0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3b phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor a, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of b cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.

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Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels.

Cited by 525 publications

References 53 publications

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats

Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life

Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance

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