Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure
Open accessAbstract
Bisphenol A (BPA) is an estrogenic endocrine disruptor widely used in the production of plastics. Increasing evidence indicates that in utero BPA exposure affects sexual differentiation and behavior; however, the mechanisms underlying these effects are unknown. We hypothesized that BPA may disrupt epigenetic programming of gene expression in the brain. Here, we provide evidence that maternal exposure during pregnancy to environmentally relevant doses of BPA (2, 20, and 200 µg/kg/d) in mice induces sex-specific, dose-dependent (linear and curvilinear), and brain region-specific changes in expression of genes encoding estrogen receptors (ERs; ERα and ERβ) and estrogen-related receptor-γ in juvenile offspring. Concomitantly, BPA altered mRNA levels of epigenetic regulators DNA methyltransferase (DNMT) 1 and DNMT3A in the juvenile cortex and hypothalamus, paralleling changes in estrogen-related receptors. Importantly, changes in ERα and DNMT expression in the cortex (males) and hypothalamus (females) were associated with DNA methylation changes in the ERα gene. BPA exposure induced persistent, largely sex-specific effects on social and anxiety-like behavior, leading to disruption of sexually dimorphic behaviors. Although postnatal maternal care was altered in mothers treated with BPA during pregnancy, the effects of in utero BPA were not found to be mediated by maternal care. However, our data suggest that increased maternal care may partially attenuate the effects of in utero BPA on DNA methylation. Overall, we demonstrate that low-dose prenatal BPA exposure induces lasting epigenetic disruption in the brain that possibly underlie enduring effects of BPA on brain function and behavior, especially regarding sexually dimorphic phenotypes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Developmental EDC exposure can lead to sex-specific changes in behavior.
“Developmental EDC exposure can also lead to sex-specific changes in behavior (Jacobsen et al., 2012; Kundakovic et al., 2013; Sobolewski et al., 2014; Williams et al., 2013).”
From The effects of prenatal PCBs on adult social behavior in rats (2015) · cites this paper as Kundakovic et al., 2013
BPA decreases Dnmt1 expression in prefrontal cortex in both male and female mice.
“Kundakovic et al . [ 49 ] | BPA | Mice; in utero | Decreases Dnmt1 expression in prefrontal cortex in both male and female mice.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
BPA alters DNA methylation of estrogen Receptor 1 in the brain.
“Also alters DNA methylation of estrogen Receptor 1 in the brain.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
BPA produces a nonmonotonic dose response for Dnmt1 expression in the hypothalamus and Dnmt3a expression in the prefrontal cortex with a U-shaped dose-response relationship observed with females whereas an inverted U-shaped dose-response relationship is observed with male mice.
“Produces a nonmonotonic dose response for Dnmt1 expression in the hypothalamus and Dnmt3a expression in the prefrontal cortex with a U-shaped dose–response relationship observed with females whereas an inverted U-shaped dose–response relationship is observed with male mice.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
Epigenetic alterations have been implicated in BPA-associated changes in pathology and function in several hormone-responsive tissues including the brain.
“Epigenetic alterations have been implicated in BPA-associated changes in pathology and function in several hormone-responsive tissues including the brain [ 49 , 130 , 138–141 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
These sexually dimorphic changes were linked to BPA-induced alterations in DNA methylation and expression of estrogen Receptor 1 in the brain.
“These sexually dimorphic changes were linked to BPA-induced alterations in DNA methylation and expression of estrogen Receptor 1 in the brain [ 49 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
Exposure to BPA reduced chasing behavior in males to levels similar to that of females and reversed the sex-dependent differences in open field behavior in distance traveled and inner area time such that each parameter was reduced in females and increased in male mice.
“Exposure to BPA reduced chasing behavior in males to levels similar to that of females and reversed the sex-dependent differences in open field behavior in distance traveled and inner area time such that each parameter was reduced in females and increased in male mice [ 49 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
In utero exposure to BPA causes sex-, dose-, and brain region-specific changes in Dnmt expression.
“In utero exposure to BPA was shown to cause sex-, dose-, and brain region-specific changes in Dnmt expression [ 49 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
High doses of BPA are associated with increasing aggressive behavior.
“High doses of BPA are also associated with increasing aggressive behavior [ 49 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
A U-shaped dose-response relationship was observed in female mice, whereas an inverted U-shaped dose-response relationship was observed in male mice.
“Interestingly, a U-shaped dose–response relationship was observed in female mice, whereas an inverted U-shaped dose–response relationship was observed in male mice [ 49 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
This same exposure paradigm produced a nonmonotonic dose response for Dnmt1 expression in the hypothalamus and Dnmt3a expression in the prefrontal cortex.
“This same exposure paradigm produced a nonmonotonic dose response for Dnmt1 expression in the hypothalamus and Dnmt3a expression in the prefrontal cortex.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
BPA exposure alters social exploratory and anxiety-like behaviors in young adult mice (P30-70) by disrupting sexually dimorphic behaviors.
“BPA exposure also alters social exploratory and anxiety-like behaviors in young adult mice (P30-70) by disrupting sexually dimorphic behaviors.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
In utero BPA exposure (2, 20, 200 μg/kg/day) significantly decreased Dnmt1 expression in the prefrontal cortex of both male and female mice.
“In utero BPA exposure (2, 20, 200 µg/kg/day) significantly decreased Dnmt1 expression in the prefrontal cortex of both male and female mice.”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses
Vandenberg, L. N., Colborn, T., Hayes, T. B., Heindel, J. J., Jacobs, D. R., Lee, D.-H., Shioda, T., Soto, A. M., vom Saal, F. S., Welshons, W. V., et al. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1050 · Cited by 3,209 · see citing works
Human exposure to bisphenol A (BPA)
Vandenberg, L. N., Hauser, R. B., Marcus, M., Olea, N., & Welshons, W. V. (2007) · Reproductive Toxicology · doi:10.1016/j.reprotox.2007.07.010 · Cited by 2,897 · see citing works
Meaney, M. J. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1161 · Cited by 2,708 · see citing works
Irizarry, R. A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., Webster, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.298 · Cited by 2,177 · see citing works
Stability and flexibility of epigenetic gene regulation in mammalian development
Reik, W. (2007) · Nature · doi:10.1038/nature05918 · Cited by 1,963 · cited 1× · see citing works
“Epigenetic gene regulation, involving posttranslational histone modifications and DNA methylation, is a process particularly sensitive to environmental cues during development (9).”
BackgroundExposure of the U.S. Population to Bisphenol A and 4- <i>tertiary</i> -Octylphenol: 2003–2004
Calafat, A. M., Ye, X., Wong, L.-Y., Reidy, J. A., & Needham, L. L. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.10753 · Cited by 1,743 · see citing works
Bisphenol-A and the Great Divide: A Review of Controversies in the Field of Endocrine Disruption
Vandenberg, L. N., Maffini, M. V., Sonnenschein, C., Rubin, B. S., & Soto, A. M. (2009) · Endocrine Reviews · doi:10.1210/er.2008-0021 · Cited by 1,407 · see citing works
Dolinoy, D. C., Huang, D., & Jirtle, R. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703739104 · Cited by 1,369 · see citing works
Integrated Risk Information System
Ord, Ncea, & Irisd (2013) · Cited by 1,172 · see citing works
In vivo effects of bisphenol A in laboratory rodent studies
Richter, C. A., Birnbaum, L. S., Farabollini, F., Newbold, R. R., Rubin, B. S., Talsness, C. E., Vandenbergh, J. G., Walser-Kuntz, D. R., & vom Saal, F. S. (2007) · Reproductive Toxicology · doi:10.1016/j.reprotox.2007.06.004 · Cited by 1,147 · see citing works
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Feng, J., Zhou, Y., Campbell, S. L., Le, T., Li, E., Sweatt, J. D., Silva, A. J., & Fan, G. (2010) · Nature Neuroscience · doi:10.1038/nn.2514 · Cited by 1,019 · see citing works
Sex-Specific Programming of Offspring Emotionality after Stress Early in Pregnancy
Mueller, B. R., & Bale, T. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1424-08.2008 · Cited by 988 · see citing works
In vitro molecular mechanisms of bisphenol A action.
Wetherill, Y. B., Akingbemi, B. T., Kanno, J., McLachlan, J. A., Nadal, A., Sonnenschein, C., Watson, C. S., Zoeller, R. T., & Belcher, S. M. (2007) · Reproductive Toxicology · doi:10.1016/j.reprotox.2007.05.010 · Cited by 920 · see citing works
Ho, S.-M., Tang, W.-Y., Belmonte de Frausto, J., & Prins, G. S. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0516 · Cited by 796 · see citing works
Reframing sexual differentiation of the brain
McCarthy, M. M., & Arnold, A. P. (2011) · Nature Neuroscience · doi:10.1038/nn.2834 · Cited by 728 · see citing works
Champagne, F. A., Weaver, I. C. G., Diorio, J., Dymov, S., Szyf, M., & Meaney, M. J. (2006) · Endocrinology · doi:10.1210/en.2005-1119 · Cited by 675 · see citing works
Self-citationDnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens
LaPlant, Q., Vialou, V., Covington, H. E., Dumitriu, D., Feng, J., Warren, B. L., Maze, I., Dietz, D. M., Watts, E. L., Iñiguez, S. D., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2619 · Cited by 612 · see citing works
Impact of Early-Life Bisphenol A Exposure on Behavior and Executive Function in Children
Braun, J. M., Kalkbrenner, A. E., Calafat, A. M., Yolton, K. A., Ye, X., Dietrich, K. N., & Lanphear, B. P. (2011) · PEDIATRICS · doi:10.1542/peds.2011-1335 · Cited by 565 · see citing works
Ogawa, S., Eng, V., Taylor, J. A., Lubahn, D. B., Korach, K. S., & Pfaff, D. W. (1998) · Endocrinology · doi:10.1210/endo.139.12.6357 · Cited by 487 · see citing works
Prenatal bisphenol A exposure and early childhood behavior.
Braun, J. M., Yolton, K., Dietrich, K. N., Hornung, R., Ye, X., Calafat, A. M., & Lanphear, B. P. (2009) · Environmental Health Perspectives · doi:10.1289/ehp.0900979 · Cited by 481 · see citing works
The Epigenetics of Sex Differences in the Brain
McCarthy, M., Auger, A., Bale, T., de Vries, G. J., Dunn, G. A., Forger, N., Murray, E. K., Nugent, B. M., Schwarz, J., & Wilson, M. E. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3331-09.2009 · Cited by 451 · see citing works
Novel Actions of Estrogen Receptor-β on Anxiety-Related Behaviors
Lund, T. D., Rovis, T., Chung, W. C. J., & Handa, R. J. (2005) · Endocrinology · doi:10.1210/en.2004-1158 · Cited by 436 · see citing works
Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system
Feng, J., Chang, H., Li, E., & Fan, G. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20404 · Cited by 401 · see citing works
US Environmental Protection Agency (1985) · PubMed · Cited by 367 · see citing works
Prenatal Bisphenol A Exposure and Child Behavior in an Inner-City Cohort
Perera, F., Vishnevetsky, J., Herbstman, J. B., Calafat, A. M., Xiong, W., Rauh, V., & Wang, S. (2012) · Environmental Health Perspectives · doi:10.1289/ehp.1104492 · Cited by 332 · see citing works
Self-citationWolstenholme, J. T., Edwards, M., Shetty, S. R. J., Gatewood, J. D., Taylor, J. A., Rissman, E. F., & Connelly, J. J. (2012) · Endocrinology · doi:10.1210/en.2012-1195 · Cited by 319 · see citing works
Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats
Kubo, K., Arai, O., Omura, M., Watanabe, R., Ogata, R., & Aou, S. (2003) · Neuroscience Research · doi:10.1016/s0168-0102(02)00251-1 · Cited by 311 · see citing works
Rubin, B. S., Lenkowski, J. R., Schaeberle, C. M., Vandenberg, L. N., Ronsheim, P. M., & Soto, A. M. (2006) · Endocrinology · doi:10.1210/en.2006-0189 · Cited by 311 · see citing works
Bromer, J. G., Zhou, Y., Taylor, M. B., Doherty, L. F., & Taylor, H. S. (2010) · The FASEB Journal · doi:10.1096/fj.09-140533 · Cited by 303 · see citing works
Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior
Skinner, M. K., Anway, M. D., Savenkova, M. I., Gore, A. C., & Crews, D. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003745 · Cited by 293 · see citing works
Epigenetic influence of social experiences across the lifespan
Champagne, F. A. (2010) · Developmental Psychobiology · doi:10.1002/dev.20436 · Cited by 273 · see citing works
Self-citationEpigenetic perspective on the developmental effects of bisphenol A
Kundaković, M., & Champagne, F. A. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.02.005 · Cited by 270 · see citing works
Self-citationPalanza, P. L., Howdeshell, K. L., Parmigiani, S., & vom Saal, F. S. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s3415 · Cited by 268 · see citing works
Minireview: Genomic Organization of the Human ERα Gene Promoter Region
Koš, M., Reid, G., Denger, S., & Gannon, F. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.12.0731 · Cited by 267 · see citing works
Goto, K., Numata, M., Komura, J., Ono, T., Bestor, T. H., & Kondo, H. (1994) · Differentiation · doi:10.1046/j.1432-0436.1994.56120039.x · Cited by 235 · see citing works
Yaoi, T., Itoh, K., Nakamura, K., Ogi, H., Fujiwara, Y., & Fushiki, S. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.09.028 · Cited by 229 · see citing works
Imwalle, D. B., Gustafsson, J.-Α., & Rissman, E. F. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.11.002 · Cited by 225 · see citing works
Schwarz, J. M., Nugent, B. M., & McCarthy, M. M. (2010) · Endocrinology · doi:10.1210/en.2010-0142 · Cited by 198 · see citing works
Neonatal genistein or bisphenol-A exposure alters sexual differentiation of the AVPV
Patisaul, H. B., Fortino, A. E., & Polston, E. K. (2006) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2005.11.004 · Cited by 195 · see citing works
Kurian, J. R., Olesen, K. M., & Auger, A. P. (2010) · Endocrinology · doi:10.1210/en.2009-0649 · Cited by 185 · see citing works
Doshi, T., Salian, S., Dighe, V. D., Balasinor, N., & Vanage, G. R. (2011) · Toxicology · doi:10.1016/j.tox.2011.07.011 · Cited by 178 · see citing works
Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice
Wolstenholme, J. T., Taylor, J. A., Shetty, S. R. J., Edwards, M., Connelly, J. J., & Rissman, E. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025448 · Cited by 168 · cited 1× · see citing works
“Similar to our findings, previous studies have shown that some aspects of social behavior are affected by BPA in a sexspecific way (46) whereas other domains are affected similarly in both sexes (47).”
ResultKhurana, S., Ranmal, S. A., & Ben‐Jonathan, N. (2000) · Endocrinology · doi:10.1210/endo.141.12.7823 · Cited by 162 · see citing works
Effects of Perinatal Exposure to Bisphenol A on Play Behavior of Female and Male Juvenile Rats
Dessì-Fulgheri, F., Porrini, S., & Farabollini, F. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s3403 · Cited by 146 · see citing works
Novikova, S. I., He, F., Bai, J., Cutrufello, N. J., Lidow, M. S., & Undieh, A. S. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001919 · Cited by 140 · see citing works
Westberry, J. M., Trout, A. L., & Wilson, M. E. (2009) · Endocrinology · doi:10.1210/en.2009-0955 · Cited by 118 · see citing works
Cao, J., Mickens, J. A., McCaffrey, K. A., Leyrer, S. M., & Patisaul, H. B. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2011.11.002 · Cited by 102 · see citing works
Roles for Oestrogen Receptor β in Adult Brain Function
Handa, R. J., Ogawa, S., Wang, J. M., & Herbison, A. E. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02206.x · Cited by 97 · see citing works
High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations
Jang, Y. J., Park, H. R., Kim, T. H., Yang, W.-J., Lee, J.-J., Choi, S. Y., Oh, S. B., Lee, E., Park, J.-H., Kim, H.-P., et al. (2012) · Toxicology · doi:10.1016/j.tox.2012.03.007 · Cited by 82 · see citing works
Monje, L. D., Varayoud, J., Muñoz‐de‐Toro, M., Luque, E. H., & Ramos, J. G. (2010) · Reproductive Toxicology · doi:10.1016/j.reprotox.2010.08.004 · Cited by 75 · see citing works
Contributions of estrogen receptor-α and estrogen receptor-β to the regulation of behavior
Tetel, M. J., & Pfaff, D. W. (2010) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2010.01.008 · Cited by 68 · see citing works
Differential expression of the estrogen receptor-related receptor γ in the mouse brain
Lorke, D. E., Süsens, U., Borgmeyer, U., et al. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00063-2 · Cited by 43 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Khurana S, Ranmal S, Ben-Jonathan N (2000) Exposure of newborn male and female rats to environmental estrogens: Delayed and sustained hyperprolactinemia and al- terations in estrogen receptor expression. Endocrinology 141(12):4512-4517.
- Ogawa S, et al. (1998) Roles of estrogen receptor-alpha gene expression in reproduction- related behaviors in female mice. Endocrinology 139(12):5070-5081.
Cited by
Sorted by citations
EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., Toppari, J., & Zoeller, R. T. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1010 · Cited by 2,407 · see citing works
Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure
Qian, X., Nguyen, H. N., Song, M. M., Hadiono, C., Ogden, S. C., Hammack, C., Yao, B., Hamersky, G. R., Jacob, F., Zhong, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.032 · Cited by 2,127 · see citing works
DNA methylation of BDNF as a biomarker of early-life adversity
Kundakovic, M., Gudsnuk, K., Herbstman, J. B., Tang, D., Perera, F. P., & Champagne, F. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408355111 · Cited by 426 · see citing works
Self-citationPalma-Gudiel, H., Córdova-Palomera, A., Eixarch, E., Deuschle, M., & Fañanás, L. (2015) · Epigenetics · doi:10.1080/15592294.2015.1088630 · Cited by 240 · see citing works
Keil, K. P., & Lein, P. J. (2016) · Environmental Epigenetics · doi:10.1093/eep/dvv012 · Cited by 167 · see citing works
Prenatal influences on temperament development: the role of environmental epigenetics
Gartstein, M. A., & Skinner, M. K. (2018) · Development and Psychopathology · doi:10.1017/s0954579417001730 · Cited by 161 · see citing works
Transgenerational effects of prenatal bisphenol A on social recognition
Wolstenholme, J. T., Goldsby, J. A., & Rissman, E. F. (2013) · Hormones and Behavior · doi:10.1016/j.yhbeh.2013.09.007 · Cited by 157 · see citing works
Immune System: An Emerging Player in Mediating Effects of Endocrine Disruptors on Metabolic Health
Bansal, A., Henao-Mejia, J., & Simmons, R. A. (2018) · Endocrinology · doi:10.1210/en.2017-00882 · Cited by 152 · see citing works
Peña, C. J., Neugut, Y. D., & Champagne, F. A. (2013) · Endocrinology · doi:10.1210/en.2013-1595 · Cited by 150 · see citing works
Self-citationDNA methylation, early life environment, and health outcomes
Mitchell, C., Schneper, L. M., & Notterman, D. A. (2016) · Pediatric Research · doi:10.1038/pr.2015.193 · Cited by 146 · see citing works
Minireview: transgenerational epigenetic inheritance: focus on endocrine disrupting compounds
Rissman, E. F., & Adli, M. (2014) · Endocrinology · doi:10.1210/en.2014-1123 · Cited by 113 · see citing works
Rijlaarsdam, J., Pappa, I., Walton, E., Bakermans-Kranenburg, M. J., Mileva-Seitz, V. R., Rippe, R. C. A., Roza, S. J., Jaddoe, V. W. V., Verhulst, F. C., Felix, J. F., et al. (2016) · Epigenetics · doi:10.1080/15592294.2016.1145329 · Cited by 97 · see citing works
Arambula, S. E., Belcher, S. M., Planchart, A., Turner, S. D., & Patisaul, H. B. (2016) · Endocrinology · doi:10.1210/en.2016-1339 · Cited by 87 · see citing works
Ecological and health issues of plastic waste
Cook, C. R., & Halden, R. U. (2020) · Plastic Waste and Recycling · doi:10.1016/b978-0-12-817880-5.00020-7 · Cited by 83 · see citing works
Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases
Maschietto, M., Bastos, L. C., Tahira, A. C., Bastos, E. P., Euclydes, V. L. V., Brentani, A., Fink, G., de Baumont, A., Felipe-Silva, A., Francisco, R. P. V., et al. (2017) · Scientific Reports · doi:10.1038/srep44547 · Cited by 78 · see citing works
Thongkorn, S., Kanlayaprasit, S., Jindatip, D., Tencomnao, T., Hu, V. W., & Sarachana, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-39386-w · Cited by 66 · see citing works
Williamson, C. M., Franks, B., & Curley, J. P. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00152 · Cited by 64 · see citing works
Self-citationThe effects of prenatal PCBs on adult social behavior in rats
Reilly, M. P., Weeks, C. D., Topper, V. Y., Thompson, L. M., Crews, D., & Gore, A. C. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.06.002 · Cited by 65 · see citing works
“Developmental EDC exposure can also lead to sex-specific changes in behavior (Jacobsen et al., 2012; Kundakovic et al., 2013; Sobolewski et al., 2014; Williams et al., 2013).”
The Relationship between Typical Environmental Endocrine Disruptors and Kidney Disease
Zhang, X., Flaws, J. A., Spinella, M. J., & Irudayaraj, J. (2022) · Toxics · doi:10.3390/toxics11010032 · Cited by 63 · see citing works
Kim, K. C., Choi, C. S., Kim, J.-W., Han, S.-H., Cheong, J. H., Ryu, J. H., & Shin, C. Y. (2016) · Molecular Neurobiology · doi:10.1007/s12035-014-8987-z · Cited by 60 · see citing works
Tyler, C. R., Hafez, A. K., Solomon, E. R., & Allan, A. M. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.07.013 · Cited by 60 · see citing works
Does Gender Leave an Epigenetic Imprint on the Brain?
Cortes, L. R., Cisternas, C. D., & Forger, N. G. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00173 · Cited by 52 · see citing works
Endocrine Disruption of Vasopressin Systems and Related Behaviors
Patisaul, H. B. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00134 · Cited by 54 · see citing works
Goldsby, J. A., Wolstenholme, J. T., & Rissman, E. F. (2017) · Endocrinology · doi:10.1210/en.2016-1188 · Cited by 48 · see citing works
Effects of maternal or paternal bisphenol A exposure on offspring behavior
Harris, E. P., Allardice, H. A., Schenk, A. K., & Rissman, E. F. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.09.017 · Cited by 33 · see citing works
Dias, G. R. M., Giusti, F. C. V., de Novais, C. O., de Oliveira, M. A. L., Paiva, A. G., Kalil-Cutti, B., Mahoney, M. M., & Graceli, J. B. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1571689 · Cited by 14 · see citing works
- Authors
- Kundakovic, M., Gudsnuk, K., Franks, B., Madrid, J., Miller, R. L., Perera, F. P., & Champagne, F. A.
- Affiliations
- Department of Psychology, Columbia University, New York, NY 10027; and
- Columbia University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-05-28
- Volume
- 110
- Issue
- 24
- Pages
- 9956-9961
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3683772
- OpenAlex
- W1968179768
- Cited by
- 490
- References
- 52
- Citations by year
- 2026: 16 · 2025: 30 · 2024: 25 · 2023: 29 · 2022: 25 · 2021: 38 · 2020: 30 · 2019: 33 · 2018: 51 · 2017: 54 · 2016: 48 · 2015: 51 · 2014: 45 · 2013: 15
- FWCI
- 38.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Environmental Protection Agency
- Blanchette Hooker Rockefeller Fund
- National Institutes of Health (1dp2od001674-01)
- National Institute of Environmental Health Sciences (5 P01 ES09600, P01ES009600)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- bisphenol A, prenatal exposure, endocrine disruptors, DNA methylation, epigenetic programming, sex differences, estrogen receptor alpha, estrogen receptor beta, estrogen-related receptor gamma, DNMT1, DNMT3A, hypothalamus, cerebral cortex, social behavior, anxiety-like behavior, maternal care
- MeSH terms
- DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3A, Bisphenol A Compounds, Animals, Base Sequence, Benzhydryl Compounds, Cerebral Cortex, DNA (Cytosine-5-)-Methyltransferases, Dose-Response Relationship, Drug, Estrogens, Non-Steroidal, Female, Hypothalamus, Male, Maternal Behavior, Molecular Sequence Data, Phenols, Pregnancy, Prenatal Exposure Delayed Effects, Sex Factors, Social Behavior, Gene Expression Regulation, Developmental, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Estrogen Receptor alpha, Estrogen Receptor beta, Mice, Endocrine Disruptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
