Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats

Fernández, Marina Olga; Bianchi, María S.; Lux‐Lantos, Victoria; Libertun, Carlos

doi:10.1289/ehp.0800267

Cited by 165 publications

(132 citation statements)

References 38 publications

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“…When treatment starts postnatally after 15 days, age at VO is not affected (Nikaido et al, 2005;Laws et al, 2000). During the age window comprised between birth and 15 days, age at VO is either not affected (Nagao et al, 1999;Adewale et al, 2009;Losa-Ward et al, 2012;Yu et al, 2010) or early (Adewale et al, 2009;Losa-Ward et al, 2012;Fernandez et al, 2009;Nah et al, 2011). A dose of 50 µg/kg causes advancement of puberty while 50 mg/kg has no effect, indicating a non-linear doseresponse relationship (Adewale et al, 2009;Losa-Ward et al, 2012).…”

Section: Female Rodentmentioning

confidence: 99%

“…There are reduced RFRP3 perika-ria, fiber density and contacts on GnRH neurons, suggesting that BPA-induced premature puberty could result from decreased inhibition of GnRH neurons. Fernandez et al have found that GnRH pulse frequency is accelerated and LH secretion reduced basally and in response to GnRH (Fernandez et al, 2009). As we have discussed in a study using DDT, reduction in LH secretion can be a developmental component of pituitary maturation before puberty and does not necessarily mean negative feedback effects (Rasier et al, 2007).…”

Section: Female Rodentmentioning

confidence: 99%

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Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

Parent

Franssen

Fudvoye

et al. 2015

Frontiers in Neuroendocrinology

160

140

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Puberty presents remarkable individual differences in timing reaching over 5 years in humans. We put emphasis on the two edges of the age distribution of pubertal signs in humans and point to an extended distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon. This suggests changing environmental influences including the possible role of nutrition, stress and endocrine disruptors. Our ability to assess neuroendocrine effects and mechanisms is very limited in humans. Using the rodent as a model, we examine the impact of environmental factors on the individual variations in pubertal timing and the possible underlying mechanisms. The capacity of environmental factors to shape functioning of the neuroendocrine system is thought to be maximal during fetal and early postnatal life and possibly less important when approaching the time of onset of puberty.

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Section: Female Rodentmentioning

confidence: 99%

Section: Female Rodentmentioning

confidence: 99%

Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

Parent

Franssen

Fudvoye

et al. 2015

Frontiers in Neuroendocrinology

160

140

View full text Add to dashboard Cite

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“…[4] It is shown that low dose of BPA increased testosterone and progesterone levels. [15,16] In another study, low dose of BPA decreased estradiol, testosterone, Cyp19 (aromatase), and StAR (steroidogenic acute regulatory protein). [17] Thus, antiestrogenic actions may responsible for the decreased responsiveness of uterus to acetylcholine.…”

Section: Discussionmentioning

confidence: 96%

Chronic ingestion of bisphenol A decreases the cholinergically evoked and spontaneous contractions of rat uterus in vitro

Gupta¹,

Deshpande²

2017

Natl J Physiol Pharm Pharmacol

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Background: Bisphenol A (BPA), a chemical used in the manufacture of plastics, has toxic effects on reproductive, developmental, and metabolic systems. It is implicated as a causative factor for infertility. The uterine and tubal contractility play a vital role in fertilization and implantation of zygote. The chronic exposure to BPA on myometrial contractions is not known. Aims and Objectives: The aim of this study is to examine the effect of chronic ingestion of BPA on rat uterine contractions evoked by acetylcholine. Materials and Methods: Rats weighing 90-150 g were fed BPA (2 µg/kg/day) or placebo containing pellets (time-matched control; TMC) orally for 28 days. The contractility of the uterus was also assessed in group of rats at the beginning (initial control [IC]). After 28 days, animals showing estrous phase were chosen for in vitro recording of uterine contractions (35 ± 1°C). Evoked contractions to different concentrations of acetylcholine were recorded followed by the effect on spontaneous contractions. Results: Acetylcholine evoked uterine contractions in vitro in a concentration-dependent manner. The contractions were similar in magnitude in IC and TMC. The uterus from BPA-fed animal exhibited decreased responsiveness to acetylcholine-evoked contractions as compared to TMC. In the presence of acetylcholine, frequency and force of spontaneous contractions increased in a concentration-dependent manner. However, in BPA-fed group, the frequency and force of spontaneous contractions were significantly attenuated. Conclusions:The results indicate that chronic exposure to BPA decreased the acetylcholine-evoked contractions as well as the spontaneous uterine contractions. The decreased contractility may account for the infertility seen after exposure to BPA.

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“…Subcutaneous administration of BPA in neonatal female rats resulted in alterations in the hypothalamic-pituitary function, i.e. decreased gonadotropin-releasing hormone-induced secretion of luteinizing hormone (Fernández et al, 2009). A differential modulation of ERα protein expression in the preoptic area of prepubertal female rats was reported for different doses of subcutaneously applied BPA: While a low dose of BPA (0.05 mg/kg b.w./day, postnatal day 1 to 7) increased the protein expression, a high BPA dose (20 mg/kg b.w./day) reduced the expression compared to controls (Monje et al, 2007).…”

Section: Effects On Receptors and Hormone Homeostasismentioning

confidence: 99%

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

Flavourings¹

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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Neonatal Exposure to Bisphenol A Alters Reproductive Parameters and Gonadotropin Releasing Hormone Signaling in Female Rats

Cited by 165 publications

References 38 publications

Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents

Chronic ingestion of bisphenol A decreases the cholinergically evoked and spontaneous contractions of rat uterus in vitro

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

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