Perinatal exposure of rats to Bisphenol A affects the fertility of male offspring

Salian, Smita; Doshi, Tanvi; Vanage, Geeta

doi:10.1016/j.lfs.2009.10.004

Cited by 233 publications

(162 citation statements)

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“…BPA is reported to have both estrogenic and antiandrogenic effects (6,23,24). Several toxicological studies (25) pointed out that rodents exposed to BPA during the prenatal or perinatal period show a large variety of adverse reproductive outcomes, including decreased epididymal weight and daily sperm production (26,27) and increased prostate weight (28), which is somewhat similar to our findings. With respect to the prepubertal or pubertal exposures, rodent studies have described a dramatic decrease in testosterone (T) levels (29,30) and epididymal sperm counts (29) after BPA exposure.…”

Section: Discussionsupporting

confidence: 90%

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Hasanluyi

Khojasteh

Nejhad

2016

Thrita

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Background: Bisphenol A is a xenoestrogen, synthesized in large quantities for the production of polymers (polycarbonates, epoxy resins) and thermal paper, and is widely used in products of everyday use (packaging, containers and bottles). Data concerning the occurrence of BPA in food, water and indoor environments as well as its appearance in tissues and body fluids of the human body are available in the literature. Male accessory sex glands are also vulnerable to environmental endocrine disruptors with adverse effects in adulthood. The developing prostate gland is particularly sensitive to estrogens and high-dose exposures during a critical developmental window results in intraepithelial prostatic neoplasia (PIN) in adult rodent models. Bisphenol A is also an endocrine disruptor. High levels of BPA exposure correlate with increased risk of mammary gland, brain and prostate cancers and have adverse effects on the tissues of the prostate and seminal vesicles. Objectives: The aim of this study was to investigate the effects of BPA doses on the histological structure and ultrastructure of prostate and seminal vesicle glands. Methods: Forty male Wistar rats were randomly divided into four groups (n = 10): A control group and three treatment groups,

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Section: Discussionsupporting

confidence: 90%

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Hasanluyi

Khojasteh

Nejhad

2016

Thrita

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“…However, abnormal spermatogenesis, reduced fertility, changes to the expression of ER alpha and Steroid Receptor Coactivator-1 in the brain have been reported to persist in male F 2 and in completely unexposed male F 3 animals after perinatal exposure to a low environmental dose of BPA [13,52]. Changes were observed even after exposure to the parent chemical had ceased.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to oestrogenic and antiandrogenic EASs, even in low doses, during the prenatal period, causes a wide spectrum of developmental, pathological and behavioural effects in the male [12,13]. If our hypothesis is correct, digit length measurement, as the anogenital distance (AGD) or anogenital index [14], is a potentially useful indicator of prenatal endocrine disruption.…”

Section: Introductionmentioning

confidence: 88%

Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

Auger¹,

Denmat

Berges

et al. 2013

Proc. R. Soc. B.

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Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D-5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.

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“…Overall, the unusual nature of the reported effects at very low doses of BPA (Salian et al 2009), coupled with incomplete reporting of results and the absence of dose response relationships makes this study unsuitable for risk assessment of BPA. Miyagawa et al (2007) analysed the behaviour (anxiogenic-like effects, motor learning and memory) and a hippocampal cholinergic marker in the adult (aged 7-11 weeks) male offspring of C57BL/6J mice (≥10 dams per group) which had been exposed throughout gestation and lactation to BPA via maternal diet (BPA doses of 0, 30 µg/kg diet and 2 g/kg diet; assuming an intake of 3 g diet/day and a body weight of 0.02 kg, this results in 0, 4.5 µg/kg b.w./day, and 300 mg/kg b.w./day).…”

Section: Other Developmental Toxicity Studiesmentioning

confidence: 94%

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2010

EFSA Journal

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Bisphenol A (BPA) is used in the manufacture of plastics, to produce reusable drinking bottles, infant feeding bottles and other food storage containers. EFSA was asked to evaluate a dietary developmental neurotoxicity study in rats (Stump, 2009) and recent scientific literature (2007)(2008)(2009)(2010) in terms of relevance for the risk assessment of BPA. The impact of these studies on the current Tolerable Daily Intake (TDI) of 0.05 mg BPA/kg body weight (b.w.)/day as set by EFSA in 2006 was assessed. Advice on the Danish risk assessment underlying the Danish ban of BPA in food contact materials for infants aged 0-3 years is included. Overall, based on this comprehensive evaluation of recent toxicity data, the Panel on food contact materials, enzymes, flavourings and processing aids (CEF) concluded that no new study could be identified, which would call for a revision of the current TDI. This TDI is based on the No-Observed-Adverse-Effect-Level (NOAEL) of 5 mg/kg b.w./day from a multi-generation reproductive toxicity study in rats, and the application of an uncertainty factor of 100. This factor is regarded as conservative based on all information on BPA toxicokinetics. The Panel noted that some studies conducted on developing animals have suggested other BPA-related effects of possible toxicological relevance, in particular biochemical changes in brain, immune-modulatory effects and enhanced susceptibility to breast tumours. These studies had several shortcomings. At present the relevance of these findings for human health cannot be assessed. Should any new relevant data become available in the future, the Panel will reconsider this opinion. A minority opinion is expressed by a Panel member and presented in an Annex to this opinion. © European Food Safety Authority, 2010 KEY WORDSBisphenol A, BPA, CAS No. 00080-05-7, developmental toxicity, neurobehaviour, low dose effects. In order to provide a global view on the risk assessment of Bisphenol A, the CEF Panel decided to address the three mandates as given above in a single opinion and postponed the adoption of this comprehensive document to 23 rd September 2010.The three different questions raised by the Commission are dealt with in three different parts (PARTS I to III) of the opinion. PART IV presents an overview of the conclusions from PARTS I to III, together with an overall conclusion. PART IThe GLP compliant study by Stump (2009) was performed according to OECD guideline 426 to address any uncertainty regarding potential neurodevelopmental effects of BPA. BPA was administered daily in the diet at concentrations of 0, 0.15, 1.5, 75, 750, and 2250 mg/kg feed to female Sprague-Dawley rats from gestational day (GD) 0 to postnatal day (PND) 21. The relative estimated intakes (in mg/kg b.w./day) were 0, 0.01, 0.12, 5.85, 56.4 and 164 during gestation and 0, 0.03, 0.25, 13.1, 129 and 410 during lactation. The CEF Panel considers this treatment schedule as relevant to human exposure in utero and via either breastfeeding or infant bottle feeding (in this...

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Perinatal exposure of rats to Bisphenol A affects the fertility of male offspring

Cited by 233 publications

References 44 publications

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Environmental levels of oestrogenic and antiandrogenic compounds feminize digit ratios in male rats and their unexposed male progeny

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