Perinatal Exposure to an Environmentally Relevant Mixture of Phthalates Results in a Lower Number of Neurons and Synapses in the Medial Prefrontal Cortex and Decreased Cognitive Flexibility in Adult Male and Female Rats

Kougias, Daniel G.; Sellinger, Elli P.; Willing, Jari; Juraska, Janice M.

doi:10.1523/jneurosci.0607-18.2018

Cited by 72Effects and risks of endocrine disrupting chemicalsSexual Differentiation and DisordersPesticide Exposure and Toxicity

Perinatal Exposure to an Environmentally Relevant Mixture of Phthalates Results in a Lower Number of Neurons and Synapses in the Medial Prefrontal Cortex and Decreased Cognitive Flexibility in Adult Male and Female Rats

Open access

Kougias, Daniel G., Sellinger, Elli P., Willing, Jari, Juraska, Janice M.·2018·The Journal of Neuroscience

DOI 10.1523/jneurosci.0607-18.2018PMC PMC6070669

Open this paper in CoChat — free account Open PDF

Abstract

The growth and organization of the developing brain are known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, such as mPFC. This region is particularly important given its involvement in executive functions and implication in the pathology of many neuropsychiatric disorders. Here, we examine the long-term effects of perinatal exposure to endocrine-disrupting compounds, the phthalates, on the mPFC and associated behavior. This investigation is pertinent as humans are ubiquitously exposed to phthalates through a variety of consumer products and phthalates can readily cross the placenta and be delivered to offspring via lactation. Pregnant dams orally consumed an environmentally relevant mixture of phthalates at 0, 200, or 1000 μg/kg/d through pregnancy and for 10 d while lactating. As adults, offspring were tested in an attentional set-shifting task, which assesses cognitive flexibility. Brains were also examined in adulthood for stereological quantification of the number of neurons, glia, and synapses within the mPFC. We found that, independent of sex, perinatal phthalate exposure at either dose resulted in a reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. Interestingly, the number of synapses was correlated with cognitive flexibility, such that rats with fewer synapses were less cognitively flexible than those with more synapses. These results demonstrate that perinatal phthalate exposure can have long-term effects on the cortex and behavior of both male and female rats. SIGNIFICANCE STATEMENT Humans globally are exposed on a daily basis to a variety of phthalates, which are endocrine-disrupting chemicals. The effects of phthalate exposure on the developing brain, especially on cognitively relevant regions, such as the mPFC, are not known. Here, we use a rat model of human prenatal exposure to an environmentally relevant mixture of phthalates and find that there is an appreciable reduction in neuron number, synapse number, and size of the mPFC and a deficit in cognitive flexibility. These results may have serious implications for humans given that the mPFC is involved in executive functions and is implicated in the pathology of many neuropsychiatric disorders.

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

Crossref · 10.1523/jneurosci.0607-18.2018

Cites

65 of 65 references verified0 citation errors · 0 not checkable

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?

Lead and other pollutants are damaging to the developing brain and PFC.
“Similarly, we can find lead and other pollutants to be damaging to the developing brain and PFC [331–334].”
From Development of prefrontal cortex (2022) · cites this paper as [332]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Dose translation from animal to human studies revisited.
Reagan‐Shaw, S., Nihal, M., & Ahmad, N. (2008) · The FASEB Journal · doi:10.1096/fj.07-9574lsf · Cited by 6,524 · see citing works
Phthalates: Toxicology and exposure
Heudorf, U., Mersch‐Sundermann, V., & Angerer, J. (2007) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2007.07.011 · Cited by 1,494 · see citing works
Stress-Induced Alterations in Prefrontal Cortical Dendritic Morphology Predict Selective Impairments in Perceptual Attentional Set-Shifting
Liston, C., Miller, M. M., Goldwater, D. S., Radley, J. J., Rocher, A. B., Hof, P. R., Morrison, J. H., & McEwen, B. S. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1184-06.2006 · Cited by 968 · see citing works
Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain
Askew, K., Li, K., Olmos-Alonso, A., Garcia-Moreno, F., Liang, Y., Richardson, P., Tipton, T., Chapman, M. A., Riecken, K., Beccari, S., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.041 · Cited by 726 · see citing works
Wired for Reproduction: Organization and Development of Sexually Dimorphic Circuits in the Mammalian Forebrain
Simerly, R. B. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142745 · Cited by 723 · see citing works
Thyroid effects of endocrine disrupting chemicals
Boas, M., Feldt‐Rasmussen, U., & Main, K. M. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.005 · Cited by 617 · see citing works
Reproductive and Developmental Toxicity of Phthalates
Lyche, J. L., Gutleb, A. C., Bergman, Å., Eriksen, G. S., Murk, A. J., Ropstad, E., Saunders, M., & Skaare, J. U. (2009) · Journal of Toxicology and Environmental Health, Part B · doi:10.1080/10937400903094091 · Cited by 607 · see citing works
The journal of neuroscience : the official journal of the Society for Neuroscience.
Press, H. (1981) · Cited by 582 · see citing works
Involvement of the Prelimbic–Infralimbic Areas of the Rodent Prefrontal Cortex in Behavioral Flexibility for Place and Response Learning
Ragozzino, M. E., Detrick, S., & Kesner, R. P. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04585.1999 · Cited by 553 · see citing works
Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data
Jonasson, Z. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.10.006 · Cited by 498 · see citing works
Prenatal phthalate exposure is associated with childhood behavior and executive functioning
Engel, S. M., Miodovnik, A., Canfield, R. L., Zhu, C., Silva, M. J., Calafat, A. M., & Wolff, M. S. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.0901470 · Cited by 441 · see citing works
An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population
Koch, H. M., Drexler, H. G., & Angerer, J. (2003) · International Journal of Hygiene and Environmental Health · doi:10.1078/1438-4639-00205 · Cited by 432 · see citing works
Childhood Exposure to Phthalates: Associations with Thyroid Function, Insulin-like Growth Factor I, and Growth
Boas, M., Frederiksen, H. W., Feldt‐Rasmussen, U., Skakkebæk, N. E., Hegedűs, L. D., Hilsted, L., Juul, A., & Main, K. M. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.0901331 · Cited by 306 · see citing works
Cytoarchitectonic development of the prefrontal cortex in the rat
van Eden, C. G., & Uylings, H. B. M. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902410302 · Cited by 306 · see citing works
Phthalate exposure and childrens neurodevelopment: A systematic review
Ejaredar, M., Nyanza, E. C., Ten Eycke, K., & Dewey, D. (2015) · Environmental Research · doi:10.1016/j.envres.2015.06.014 · Cited by 293 · see citing works
Differential effects of phthalate esters on transcriptional activities via human estrogen receptors α and β, and androgen receptor
Takeuchi, S., Iida, M., Kobayashi, S., Jin, K., Matsuda, T., & Kojima, H. (2005) · Toxicology · doi:10.1016/j.tox.2005.02.002 · Cited by 287 · see citing works
Prenatal phthalate exposure and reduced masculine play in boys
Swan, S. H., Liu, F., Hines, M., Kruse, R. L., Wang, C., Redmon, J. B., Sparks, A., & Weiss, B. (2010) · International Journal of Andrology · doi:10.1111/j.1365-2605.2009.01019.x · Cited by 257 · see citing works
Meta-analysis of neuropsychological measures of executive functioning in children and adolescents with high-functioning autism spectrum disorder
Lai, C. L. E., Lau, Z., Lui, S. S. Y., Lok, E., Tam, V., Chan, Q., Cheng, K. M., Lam, S. M., & Cheung, E. F. C. (2017) · Autism Research · doi:10.1002/aur.1723 · Cited by 250 · see citing works
Learning During Stressful TimesPreprint
Shors, T. J. (2004) · Learning & Memory · doi:10.1101/lm.66604 · Cited by 245 · see citing works
Neuron number decreases in the rat ventral, but not dorsal, medial prefrontal cortex between adolescence and adulthood
Markham, J. A., Morris, J. R., & Juraska, J. M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.10.015 · Cited by 230 · see citing works
Self-citation
Distribution of estrogen receptor alpha and beta immunoreactive profiles in the postnatal rat brain
Pérez, S. E., Chen, E.-Y., & Mufson, E. J. (2003) · Developmental Brain Research · doi:10.1016/s0165-3806(03)00223-2 · Cited by 228 · see citing works
Prenatal Phthalate Exposures and Neurobehavioral Development Scores in Boys and Girls at 6–10 Years of Age
Kobrosly, R. W., Evans, S. F., Miodovnik, A., Barrett, E. S., Thurston, S. W., Calafat, A. M., & Swan, S. H. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307063 · Cited by 204 · see citing works
Prenatal Exposure to Phthalate Esters and Behavioral Syndromes in Children at 8 Years of Age: Taiwan Maternal and Infant Cohort Study
Lien, Y., Ku, H., Su, P., Chen, S.-J., Chen, H.-Y., Liao, P., Chen, W. J., & Wang, S. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307154 · Cited by 177 · see citing works
Synaptic number changes in the medial prefrontal cortex across adolescence in male and female rats: a role for pubertal onset
Drzewiecki, C. M., Willing, J., & Juraska, J. M. (2016) · Synapse · doi:10.1002/syn.21909 · Cited by 168 · see citing works
Self-citation
More Is Less: A Disinhibited Prefrontal Cortex Impairs Cognitive Flexibility
Gruber, A. J., Calhoon, G. G., Shusterman, I., Schoenbaum, G., Roesch, M. R., & O'Donnell, P. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4623-10.2010 · Cited by 160 · see citing works
Deficient Social and Play Behavior in Juvenile and Adult Rats after Neonatal Cortical Lesion: Effects of Chronic Pubertal Cannabinoid Treatment
Schneider, M., & Koch, M. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300634 · Cited by 160 · see citing works
Gender and racial/ethnic differences in the associations of urinary phthalate metabolites with markers of diabetes risk: national health and nutrition examination survey 2001–2008
Huang, T., Saxena, A. R., ISGANAITIS, E. M., & James-Todd, T. M. (2014) · Environmental Health · doi:10.1186/1476-069x-13-6 · Cited by 139 · see citing works
Dibutyl phthalate (DBP)-induced apoptosis and neurotoxicity are mediated via the aryl hydrocarbon receptor (AhR) but not by estrogen receptor alpha (ERα), estrogen receptor Beta (ERβ), or peroxisome proliferator-activated receptor gamma (PPARγ) in mouse cortical neurons
Wójtowicz, A. K., Szychowski, K. A., Wnuk, A., & Kajta, M. (2017) · Neurotoxicity Research · doi:10.1007/s12640-016-9665-x · Cited by 129 · see citing works
Cumulative effects of antiandrogenic chemical mixtures and their relevance to human health risk assessment
Howdeshell, K. L., Hotchkiss, A. K., & Gray, L. E. (2016) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2016.11.007 · Cited by 128 · see citing works
Time- and Dose-Related Effects of Di-(2-ethylhexyl) Phthalate and Its Main Metabolites on the Function of the Rat Fetal Testis in Vitro
Chauvigné, F., Menuet, A., Lesné, L., Chagnon, M., Chevrier, C., Regnier, J.-F., Angerer, J., & Jégou, B. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11870 · Cited by 123 · see citing works
Organizational action of estrogen on synaptic pattern in the amygdala: implications for sexual differentiation of the brain
Nishizuka, M., & Arai, Y. (1981) · Brain Research · doi:10.1016/0006-8993(81)90247-x · Cited by 120 · see citing works
Transplacental Transfer of Monomethyl Phthalate and Mono(2-ethylhexyl) Phthalate in a Human Placenta Perfusion System
Mose, T., Knudsen, L. E., Hedegaard, M. S., & Mortensen, G. K. (2007) · International Journal of Toxicology · doi:10.1080/10915810701352721 · Cited by 117 · see citing works
Neurotoxicity of dibutyl phthalate in brain development following perinatal exposure: A study in rats
Li, X., Jiang, L., Chen, L., Chen, H., & Li, X. (2013) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2013.05.001 · Cited by 106 · see citing works
Gonadectomy before puberty increases the number of neurons and glia in the medial prefrontal cortex of female, but not male, rats
Koss, W. A., Lloyd, M. M., Sadowski, R. N., Wise, L. M., & Juraska, J. M. (2015) · Developmental Psychobiology · doi:10.1002/dev.21290 · Cited by 96 · see citing works
Self-citation
Control of Cell Number in the Sexually Dimorphic Brain and Spinal Cord
Forger, N. G. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01825.x · Cited by 95 · see citing works
Antiandrogenic activity of phthalate mixtures: Validity of concentration addition
Christen, V., Crettaz, P., Oberli-Schrämmli, A., & Fent, K. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2011.12.021 · Cited by 86 · see citing works
Phthalates and neurotoxic effects on hippocampal network plasticity
Holahan, M. R., & Smith, C. A. (2015) · NeuroToxicology · doi:10.1016/j.neuro.2015.02.008 · Cited by 85 · see citing works
NEONATAL EXPOSURE TO DI(N-BUTYL) PHTHALATE (DBP) ALTERS MALE REPRODUCTIVE-TRACT DEVELOPMENT
Kim, H. S., Kim, T. S., Shin, J., Moon, H. J., Kang, I. H., Kim, I. Y., Oh, J. Y., & Han, S. Y. (2004) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390490514859 · Cited by 84 · see citing works
Behavioral and morphological alterations following neonatal excitotoxic lesions of the medial prefrontal cortex in rats
Schneider, M., & Koch, M. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.04.014 · Cited by 83 · see citing works
Effects of uterine and lactational exposure to di-(2-ethylhexyl) phthalate on spatial memory and NMDA receptor of hippocampus in mice
Dai, Y., Yang, Y., Xu, X., & Hu, Y. (2015) · Hormones and Behavior · doi:10.1016/j.yhbeh.2015.03.008 · Cited by 81 · see citing works
Proposed Mode of Action for In Utero Effects of Some Phthalate Esters on the Developing Male Reproductive Tract
David, R. M. (2006) · Toxicologic Pathology · doi:10.1080/01926230600642625 · Cited by 79 · see citing works
Effects of stress on behavioral flexibility in rodents
Hurtubise, J. L., & Howland, J. G. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.04.007 · Cited by 79 · see citing works
Association between phthalates and externalizing behaviors and cortical thickness in children with attention deficit hyperactivity disorder
Park, S. J., Lee, J.-M., Kim, J.-W., Cheong, J. H., Yun, H. J., Hong, Y., Kim, Y., Han, D. H., Yoo, H., Shin, M., et al. (2014) · Psychological Medicine · doi:10.1017/s0033291714002694 · Cited by 78 · see citing works
Sexual differentiation of synaptic connectivity and neuronal plasma membrane in the arcuate nucleus of the rat hypothalamus
Pe´rez, J., Naftolin, F. N., & García‐Segura, L. M. (1990) · Brain Research · doi:10.1016/0006-8993(90)91068-r · Cited by 77 · see citing works
The role of phthalate esters in autism development: A systematic review
Jeddi, M. Z., Janani, L., Memari, A. H., Akhondzadeh, S., & yunesian, M. (2016) · Environmental Research · doi:10.1016/j.envres.2016.08.021 · Cited by 76 · see citing works
Plasticity in the prefrontal cortex of adult rats
Kolb, B. E., & Gibb, R. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00015 · Cited by 73 · see citing works
Androgens reduce cell death in the developing rat visual cortex
Nuñez, J. L., Jurgens, H. A., & Juraska, J. M. (2000) · Developmental Brain Research · doi:10.1016/s0165-3806(00)00126-7 · Cited by 73 · see citing works
Self-citation
Effects of neonatal lesions of the medial prefrontal cortex on adult rat behaviour
Schwabe, K., Enkel, T., Klein, S., Schütte, M., & Koch, M. (2003) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.10.030 · Cited by 68 · see citing works
Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland
Dostal, L. A., Weaver, R. P., & Schwetz, B. A. (1987) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(87)90054-8 · Cited by 64 · see citing works
Activation of Trim17 by PPARγ is involved in Di(2-ethylhexyl) phthalate (DEHP)-induced apoptosis on Neuro-2a cells
Lin, C.-H., Chen, T., Chen, S.-S., Hsiao, P.-C., & Yang, R.-C. (2011) · Toxicology Letters · doi:10.1016/j.toxlet.2011.08.002 · Cited by 61 · see citing works
A generalized linear mixed model for longitudinal binary data with a marginal logit link function
Parzen, M., Ghosh, S., Lipsitz, S. R., Sinha, D., Fitzmaurice, G. M., Mallick, B. K., & Ibrahim, J. G. (2011) · The Annals of Applied Statistics · doi:10.1214/10-aoas390 · Cited by 61 · see citing works
Mono-(2-ethylhexyl) phthalate impairs neurodevelopment: Inhibition of proliferation and promotion of differentiation in PC12 cells
Chen, T. X., Yang, W., Li, Y., Chen, X., & Xu, S. (2010) · Toxicology Letters · doi:10.1016/j.toxlet.2010.12.002 · Cited by 61 · see citing works
Di-(2-Ethylhexyl) Phthalate Metabolites in Urine Show Age-Related Changes and Associations with Adiposity and Parameters of Insulin Sensitivity in Childhood
Smerieri, A., Testa, C., Lazzeroni, P., Nuti, F., Grossi, E., Cesari, S., Montanini, L., Latini, G., Bernasconi, S., Papini, A. M., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117831 · Cited by 56 · see citing works
Effects of Perinatal Exposure to Phthalates and a High-Fat Diet on Maternal Behavior and Pup Development and Social Play
Kougias, D. G., Cortes, L. R., Moody, L., Rhoads, S., Pan, Y., & Juraska, J. M. (2017) · Endocrinology · doi:10.1210/en.2017-03047 · Cited by 50 · see citing works
Self-citation
Progesterone Receptor Expression in the Developing Mesocortical Dopamine Pathway: Importance for Complex Cognitive Behavior in Adulthood
Willing, J., & Wagner, C. K. (2016) · Neuroendocrinology · doi:10.1159/000434725 · Cited by 45 · see citing works
Self-citation
Prenatal exposure to di(2-ethylhexyl) phthalate impairs development of the mouse neocortex
Komada, M., Gendai, Y., Kagawa, N., & Nagao, T. (2016) · Toxicology Letters · doi:10.1016/j.toxlet.2016.07.019 · Cited by 43 · see citing works
Age- and Sex-Dependent Changes in Androgen Receptor Expression in the Developing Mouse Cortex and Hippocampus
Tsai, H., Taniguchi, S., Samoza, J., & Ridder, A. (2015) · Neuroscience Journal · doi:10.1155/2015/525369 · Cited by 36 · see citing works
Urinary bisphenol-A, phthalate metabolites and body composition in US adults, NHANES 1999–2006
Corbasson, I., Hankinson, S. E., Stanek, E. J., & Reeves, K. W. (2016) · International Journal of Environmental Health Research · doi:10.1080/09603123.2016.1233524 · Cited by 34 · see citing works
Regulation of estrogen receptor alpha gene expression in the mouse prefrontal cortex during early postnatal development
Westberry, J. M., & Wilson, M. E. (2012) · Neurogenetics · doi:10.1007/s10048-012-0323-z · Cited by 33 · see citing works
The G protein-coupled cannabinoid-1 (CB1) receptor of mammalian brain: Inhibition by phthalate esters in vitro
Bisset, K. M., Dhopeshwarkar, A., Liao, C., & Nicholson, R. A. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.06.019 · Cited by 29 · see citing works
Comparative suppression of phthalate monoesters and phthalate diesters on calcium signalling coupled to nicotinic acetylcholine receptors
Liu, P., Tseng, F.-W., & Liu, J.-H. (2009) · The Journal of Toxicological Sciences · doi:10.2131/jts.34.255 · Cited by 27 · see citing works
Perinatal exposure to benzyl butyl phthalate induces alterations in neuronal development/maturation protein expression, estrogen responses, and fear conditioning in rodents
DeBartolo, D., Jayatilaka, S., Siu, N. Y., Rose, M., Ramos, R. L., & Betz, A. J. (2015) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000190 · Cited by 23 · see citing works
Sex differences in learning and memory following short‐term dietary restriction in the rat
Rajab, E., Alqanbar, B., Naiser, M. J., Abdulla, H. A., Al‐Momen, M. M., & Kamal, A. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.05.011 · Cited by 19 · see citing works
[Cognitive flexibility, an additional symptom of attention deficit hyperactivity disorder. Is it a therapeutically predictive element?].
Etchepareborda, M. C., & Mulas, F. (2004) · PubMed · Cited by 8 · see citing works
Turnover of glial cells in the central nervous system
Hattori, T., Hamada, S., Masaki, Τ., Kushima, R., Ohmura, M., Kataoka, Y., Ikehara, Y., Kita, M., & Magami, Y. (1989) · Biomedical Research-tokyo · Cited by 8 · see citing works

Flagged first, then by citations

Sorted by citations

Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378 · see citing works
Neurotoxicity of Ortho-Phthalates: Recommendations for Critical Policy Reforms to Protect Brain Development in Children
Engel, S. M., Patisaul, H. B., Brody, C., Hauser, R. B., Zota, A. R., Bennet, D. H., Swanson, M., & Whyatt, R. M. (2021) · American Journal of Public Health · doi:10.2105/ajph.2020.306014 · Cited by 97 · see citing works
Exposure to phthalates impaired neurodevelopment through estrogenic effects and induced DNA damage in neurons
Xu, S., Zhang, H., Pao, P., Lee, A., Wang, J., Chan, Y. S., Manno, F. A. M., Chan, S., Cheng, S. H., & Chen, X. (2020) · Aquatic Toxicology · doi:10.1016/j.aquatox.2020.105469 · Cited by 79 · see citing works
The detrimental effect of microplastics on critical periods of development in the neuroendocrine system
Solleiro-Villavicencio, H., de León, C. T. G., Río‐Araiza, V. H. D., & Morales‐Montor, J. (2020) · Birth Defects Research · doi:10.1002/bdr2.1776 · Cited by 80 · see citing works
Identifying periods of susceptibility to the impact of phthalates on children's cognitive abilities
Li, N., Papandonatos, G. D., Calafat, A. M., Yolton, K. A., Lanphear, B. P., Chen, A., & Braun, J. M. (2019) · Environmental Research · doi:10.1016/j.envres.2019.03.009 · Cited by 69 · see citing works
“decreased cognitive flexibility in adult rats (Kougias et al., 2018), which supports our observations.”
Result
Domain- and trimester-specific effect of prenatal phthalate exposure on preschooler cognitive development in the Ma’anshan Birth Cohort (MABC) study
Zhu, Y., Wu, X., Yan, S., Huang, K., Tong, J., Gao, H., Xie, Y., Tao, S., Ding, P., Zhu, P., et al. (2020) · Environment International · doi:10.1016/j.envint.2020.105882 · Cited by 62 · see citing works
Sex-biased impact of endocrine disrupting chemicals on behavioral development and vulnerability to disease: Of mice and children
Palanza, P., Paterlini, S., Brambilla, M., Ramundo, G., Caviola, G., Gioiosa, L., Parmigiani, S., Saal, F. S. V., & Ponzi, D. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.11.015 · Cited by 59 · see citing works
Perinatal exposure to endocrine disrupting chemicals and neurodevelopment: How articles of daily use influence the development of our children
O’Shaughnessy, K. L., Fischer, F., & Zenclussen, A. C. (2021) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2021.101568 · Cited by 45 · see citing works
Phthalate exposure and neurodevelopmental outcomes in early school age children from Poland
Jankowska, A., Polańska, K., Koch, H. M., Pälmke, C., Waszkowska, M., Stańczak, A., Wesołowska, E., Hanke, W., Böse‐O’Reilly, S., Calamandrei, G., et al. (2019) · Environmental Research · doi:10.1016/j.envres.2019.108829 · Cited by 38 · see citing works
White matter microstructure mediates the association between prenatal exposure to phthalates and behavior problems in preschool children
England-Mason, G., Grohs, M. N., Reynolds, J. E., MacDonald, A. M., Kinniburgh, D. W., Liu, J., Martin, J. W., Lebel, C. A., & Dewey, D. (2019) · Environmental Research · doi:10.1016/j.envres.2019.109093 · Cited by 37 · see citing works
“Although animal studies show that prenatal exposure to EDCs affects brain development (Itoh et al., 2012; Kougias et al., 2018; Masuo & Ishido, 2011), to our knowledge, this is the first study to show that prenatal phthalate exposure is related to brain structure in children.”
Background
Effects of postnatal exposure to phthalate, bisphenol a, triclosan, parabens, and per- and poly-fluoroalkyl substances on maternal postpartum depression and infant neurodevelopment: a korean mother-infant pair cohort study
Kim, J. H., Moon, N., Ji, E. S., & Moon, H. (2023) · Environmental Science and Pollution Research · doi:10.1007/s11356-023-29292-0 · Cited by 36 · see citing works
“Finally, long-term exposure to phthalates can decrease neuron and synapse numbers in the medial prefrontal cortex (Kougias et al. 2018).”
Background
An Integrated Review of Recent Research on the Relationships Between Religious Belief, Political Ideology, Authoritarianism, and Prejudice
Cuevas, J. A., & Dawson, B. L. (2020) · Psychological Reports · doi:10.1177/0033294120925392 · Cited by 31 · see citing works
“…an array of animal species including mice (Marwari & Dawe, 2018; Morris-Schaffer, et al., 2018; Piantadosi et al., 2019), rats (Dhawan et al., 2019; Kougias et al., 2018; Zhang et al., 2017), rhesus monkeys (Shnitko et al., 2019), chimpanzees (Lacreuse et al., 2018), horses (Fortin et al., 2018),…”
Background
Prenatal exposure to common plasticizers: a longitudinal study on phthalates, brain volumetric measures, and IQ in youth
Ghassabian, A., van den Dries, M. A., Trasande, L., Lamballais, S., Spaan, S., Martinez-Moral, M.-P., Kannan, K., Jaddoe, V. W. V., Engel, S. M., Pronk, A., et al. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02225-6 · Cited by 27 · see citing works
Behavioral Effects of Exposure to Phthalates in Female Rodents: Evidence for Endocrine Disruption?
Adam, N., & Mhaouty‐Kodja, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052559 · Cited by 27 · see citing works
“2 Composition of the mixture in [72,84]: 35% DEP, 21% DEHP, 15% DBP, 15% DiNP, 8% DiBP, 5% BBP.”
BackgroundInfluential
The last stage of development: The restructuring and plasticity of the cortex during adolescence especially at puberty
Juraska, J. M. (2024) · Developmental Psychobiology · doi:10.1002/dev.22468 · Cited by 29 · see citing works
Self-citation
Behavioral effects in adult rats exposed to low doses of a phthalate mixture during the perinatal or adolescent period
Sellinger, E. P., Kougias, D. G., Drzewiecki, C. M., & Juraska, J. M. (2020) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2020.106886 · Cited by 23 · see citing works
Self-citation
Recovery of BDNF and CB1R in the Prefrontal Cortex Underlying Improvement of Working Memory in Prenatal DEHP-Exposed Male Rats after Aerobic Exercise
Wang, D., Lin, H., Lee, Y.-J., Yu, H.-F., Wu, S.-R., & Qamar, M. U. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113867 · Cited by 25 · see citing works
“A study regarding the prefrontal function shows that perinatal exposure to a mixture of phthalates results in a deficit in cognitive flexibility [48].”
Background
Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort
Dewey, D., Martin, J. W., MacDonald, A. M., Kinniburgh, D. W., Letourneau, N. L., Giesbrecht, G. F., Field, C. J., Bell, R. C., & England-Mason, G. (2023) · NeuroToxicology · doi:10.1016/j.neuro.2023.07.005 · Cited by 24 · see citing works
Plasticizers in the neonatal intensive care unit: A review on exposure sources and health hazards
Panneel, L., Malarvannan, G., Jorens, P. G., Covaci, A., & Mulder, A. (2021) · Critical Reviews in Environmental Science and Technology · doi:10.1080/10643389.2021.1970455 · Cited by 22 · see citing works
“…studies in rodents also showed prenatal DEHP exposure to influence the cortical regions by reducing the neocortical proliferation and neurogenesis (Komada et al., 2016), resulting in a reduction in neuron and synapse numbers and reduced size of the prefrontal cortex (Kougias et al., 2018).”
Background
Effects of diisopentyl phthalate exposure during gestation and lactation on hormone‐dependent behaviours and hormone receptor expression in rats
da Silva, G. N., Curi, T. Z., Tolouei, S. E. L., Passoni, M. T., Hey, G. B. S., Romano, R. M., Martino‐Andrade, A. J., & Dalsenter, P. R. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12816 · Cited by 21 · see citing works
Nuclear Receptors-Mediated Endocrine Disrupting Effects of Non-Phthalate Plasticizers: A Review
Yu, J., Zou, H., Zhang, T., & Zhang, J. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c04060 · Cited by 21 · see citing works
Prenatal urinary concentrations of phthalate metabolites and behavioral problems in Mexican children: The Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) study
Colicino, E., de Water, E., Just, A. C., Navarro, E., Pedretti, N. F., McRae, N., Braun, J. M., Schnaas, L., Rodríguez‐Carmona, Y., Hernández, C., et al. (2021) · Environmental Research · doi:10.1016/j.envres.2021.111338 · Cited by 20 · see citing works
Prenatal exposure to phthalates and its effects upon cognitive and motor functions: A systematic review
Martínez, M., Alegre-Martínez, A., & Cauli, O. (2021) · Toxicology · doi:10.1016/j.tox.2021.152980 · Cited by 20 · see citing works
Disrupted Prenatal Metabolism May Explain the Etiology of Suboptimal Neurodevelopment: A Focus on Phthalates and Micronutrients and their Relationship to Autism Spectrum Disorder
Parenti, M., & Slupsky, C. M. (2024) · Advances in Nutrition · doi:10.1016/j.advnut.2024.100279 · Cited by 18 · see citing works
Cognitive and hippocampal effects of adult male mice exposure to environmentally relevant doses of phthalates
Ducroq, S., Duplus, E., Grange‐Messent, V., Trivelloni, F., Penalva-Mousset, L., Petropoulos, I., & Mhaouty‐Kodja, S. (2023) · Environmental Pollution · doi:10.1016/j.envpol.2023.121341 · Cited by 19 · see citing works
Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia
Neyama, H., Wu, Y., Nakaya, Y., Kato, S., Shimizu, T., Tahara, T., Shigeta, M., Inoue, M., Miyamichi, K., Matsushita, N., et al. (2025) · Science Advances · doi:10.1126/sciadv.adp8494 · Cited by 19 · see citing works
“7 (D to G), the counting area of layer V is defined as in previous reports ( 87 , 88 ).”
Perinatal phthalate exposure increases developmental apoptosis in the rat medial prefrontal cortex
Sellinger, E. P., Riesgo, V. R., Brinks, A. S., Willing, J., & Juraska, J. M. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.09.007 · Cited by 16 · see citing works
Self-citation
Di-2-ethylhexyl phthalate affects zinc metabolism and neurogenesis in the developing rat brain
Liu, X., Adamo, A. M., & Oteiza, P. I. (2022) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2022.109351 · Cited by 16 · see citing works
Endocrine-Disrupting Chemicals and Hippocampal Development: The Role of Estrogen and Androgen Signaling
Lupu, D.-I., Cediel-Ulloa, A., & Rüegg, J. (2023) · Neuroendocrinology · doi:10.1159/000531669 · Cited by 13 · see citing works
“Exposure to phthalates has been associated with neurodevelopmental problems in children [22, 163 – 166] and impaired neurogenesis in vivo and in vitro [167, 168].”
Background
Brief postnatal exposure to bisphenol A affects apoptosis and gene expression in the medial prefrontal cortex and social behavior in rats with sex specificity
Drzewiecki, C. M., Brinks, A. S., Sellinger, E. P., Doshi, A., Koh, J. Y., & Juraska, J. M. (2022) · NeuroToxicology · doi:10.1016/j.neuro.2022.11.011 · Cited by 12 · see citing works
Self-citation
Paternal and maternal preconception and maternal pregnancy urinary phthalate metabolite and BPA concentrations in relation to child behavior
Leader, J. E., Mínguez‐Alarcón, L., Williams, P. L., Ford, J. B., Dadd, R., Chagnon, O., Bellinger, D. C., Oken, E., Calafat, A. M., Hauser, R. B., et al. (2023) · Environment International · doi:10.1016/j.envint.2023.108337 · Cited by 12 · see citing works
“…and BPA was associated with alterations in multiple biological pathways that may influence neurodevelopment, including altered hormone homeostasis (e.g., thyroid and gonadal) and alteration of brain lipid metabolism (Kougias et al., 2018; Li et al., 2013; Sun et al., 2014; Gore et al., 2019).”
Background
Exposure to Low Doses of Phthalates in Male Rodents: Effects on Reproductive and Cognitive Behaviors
Ducroq, S., Grange‐Messent, V., & Mhaouty‐Kodja, S. (2023) · Neuroendocrinology · doi:10.1159/000534836 · Cited by 11 · see citing works
“…neural modi ﬁ cations involve neuropeptides or receptors related to sex steroids, insulin, and insulin growth factor (IGF) 1/IGF 2, or Avp systems [15, 19, 23, 28], as well as neurotransmitters, pre-and postsynaptic proteins, and mediators [18, 23], or proin ﬂ ammatory proteins such as COX-2 [21].”
Background
Cell death in the male and female rat medial prefrontal cortex during early postnatal development
Sellinger, E. P., Drzewiecki, C. M., Willing, J., & Juraska, J. M. (2021) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2021.03.002 · Cited by 10 · see citing works
Self-citation
Housing Environment Affects Pubertal Onset, Anxiety-like Behavior, and Object Interaction in Male and Female Long Evans Rats
Vogt, M. E., Riesgo, V. R., Flanigan, K. A. S., & Willing, J. (2022) · Journal of the American Association for Laboratory Animal Science · doi:10.30802/aalas-jaalas-21-000119 · Cited by 10 · see citing works
Self-citation
Developmental neurotoxicity evaluation of di(2-ethylhexyl) phthalate (DEHP) and three alternative plasticizers in human neurospheres
Kühne, B. A., Klose, J., Seeger, B., Illa, M., Muñoz‐Torrero, D., Koch, K., Fritsche, E., & Barenys, M. (2025) · Environment International · doi:10.1016/j.envint.2025.110005 · Cited by 10 · see citing works
Associations of prenatal phthalate exposure with neurobehavioral outcomes in 4.5- and 7.5-month-old infants
Sprowles, J. L. N., Dzwilewski, K. L. C., Merced‐Nieves, F. M., Musaad, S. M. A., Schantz, S. L., & Geiger, S. D. (2022) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2022.107102 · Cited by 10 · see citing works
Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats
Drzewiecki, C. M., Willing, J., Cortes, L. R., & Juraska, J. M. (2021) · Developmental Psychobiology · doi:10.1002/dev.22111 · Cited by 9 · see citing works
Self-citation
Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family
Štefánik, P., Morová, M., & Herichová, I. (2024) · Biomedicines · doi:10.3390/biomedicines12020424 · Cited by 7 · see citing works
“Phthalate uptake is associated with abnormalities in reproductive tract development [55,56], brain development [57] and behavioural changes [58,59] and can promote carcinogenesis [60,61].”
Background
Combining metabolomics with bioanalysis methods to investigate the potential toxicity of dihexyl phthalate
Song, D., Xu, C., Holck, A. L., & Liu, R. (2020) · Environmental Toxicology · doi:10.1002/tox.23027 · Cited by 7 · see citing works
“A previous study reported that exposure to phthalate mixtures or metabolites of phthalates induced abnormal cognitive ability in adult rats.(64,65) So, the increase of glycerophospholipids may”
Background
Impact of endocrine disruptors from mother's diet on immuno-hormonal orchestration of brain development and introduction of the Virtual Human Twin tool.
Fucic, A., Mantovani, A., Vena, J., Bloom, M., Sinčić, N., Vázquez, M., & Aguado-Sierra, J. (2023) · Reproductive Toxicology · doi:10.1016/j.reprotox.2023.108357 · Cited by 6 · see citing works
Prenatal Di‐methoxyethyl phthalate exposure impairs cortical neurogenesis and synaptic activity in the mice
Ko, M. Y., Park, H.-J., Chon, S., Lee, B., Cha, S., Hyun, S., & Ka, M. (2023) · Brain Pathology · doi:10.1111/bpa.13221 · Cited by 6 · see citing works
“Additionally, our findings were consistent with previous findings that prenatal phthalate mixture exposure resulted in a reduction in neuron number of the medial prefrontal cortex (mPFC) in rats [36].”
BackgroundResult
Autistic-Like Traits in Laboratory Rodents Exposed to Phthalic Acid Esters During Early Development – an Animal Model of Autism?
Morová, M., & Kršková, L. (2021) · Physiological Research · doi:10.33549/physiolres.934570 · Cited by 6 · see citing works
“Kougias et al. 2018b DEP, DEHP, DBP, DiNP, DiBP, BBP; 0, 200, or 1000 µg/kg/day GD 2 - PND 10 LongEvans hooded rats Social play behavior 200 mg phthalates/kg: close to significant decrease in social play.”
BackgroundInfluential
Exploring associations between urine levels of phthalates and autism spectrum disorder symptoms: a case–control study in Tianjin, China
Han, Y., Jin, S., Liu, L., Qu, Z., Gao, L., Li, P., Xiong, W., & Zhang, X. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-022-21526-x · Cited by 6 · see citing works
“Animal studies have shown that phthalate exposure results in a reduction in neuron number, synapse number, and size of the medial prefrontal cortex and a deficit in cognitive function (Kougias et al. 2018).”
Background
Changes in sex differences in neuroanatomical structure and cognitive behavior across the life spanPreprint
Juraska, J. M. (2022) · Learning & Memory · doi:10.1101/lm.053499.121 · Cited by 6 · see citing works
“Asmentioned previously,males www.learnmem.org 344 Learning & Memory (in both the control and perinatal phthalate-exposed groups) perform better than females on an extradimensional shift task, which is concordant with structural differences (Kougias et al. 2018).”
InfluentialSelf-citation
A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores
Yu, E. X., Braun, J. M., Lyall, K., Hertz‐Picciotto, I., Fallin, M. D., Croen, L., Chen, A., Xu, Y. Y., Yolton, K. A., Newschaffer, C. J., et al. (2023) · Epidemiology · doi:10.1097/ede.0000000000001682 · Cited by 5 · see citing works
“…have found that urinary phthalate metabolite concentrations during pregnancy caused abnormal social behaviors, 12 emotional instability, 13 damage in spatial and learning memory, 14,15 decreased cognitive flexibility, 16 and increased anxiety, 15 all of which contribute to ASD diagnoses in humans.”
Background
A role for adverse childhood experiences and depression in preeclampsia
Myers, M. C., Gumusoglu, S. B., Brandt, D. S., Stroud, A., Hunter, S. K., Vignato, J. A., Nuckols, V. R., Pierce, G. L., Santillan, M. K. O., & Santillan, D. A. (2024) · Journal of Clinical and Translational Science · doi:10.1017/cts.2023.704 · Cited by 5 · see citing works
Environmentally relevant DEHP exposure during gestational and lactational period inhibits filamin a testicular expression
Pérez, P. A., Toledo, J., Vitellini, F., Cuello, V. N., Cantarelli, V. I., Ponzio, M. F., Mukdsi, J. H., & Gutiérrez, S. (2023) · Journal of Molecular Histology · doi:10.1007/s10735-023-10144-7 · Cited by 5 · see citing works
“200 µg / kg dose in rats is equivalent to a human dose of 32.43 µg/kg (Kougias et al. 2018).”
MethodInfluential
Timing of Methamphetamine Exposure during Adolescence Differentially Influences Parvalbumin and Perineuronal Net Immunoreactivity in the Medial Prefrontal Cortex of Female, but Not Male, Rats
Brinks, A. S., Carrica, L. K., Tagler, D. J., Gulley, J. M., & Juraska, J. M. (2024) · Developmental Neuroscience · doi:10.1159/000538608 · Cited by 6 · see citing works
“The area of the mPFC was traced on each section of tissue as in our previous work [25, 26].”
Self-citation
Children’s exposure to chemical contaminants: Demographic disparities and associations with the developing basal ganglia
Fowler, C. H., Reuben, A., Stapleton, H. M., Hoffman, K., Herkert, N. J., Barakat, L., & Gaffrey, M. S. (2024) · Environmental Research · doi:10.1016/j.envres.2024.119990 · Cited by 4 · see citing works
Natural bioactive compounds as therapeutic agents against phthalate neurotoxicity: Cellular and molecular signaling pathways
Atanda, O. E., Da‐Silva, O. F., Akanbi, P., Aschner, M., & Adedara, I. A. (2026) · NeuroToxicology · doi:10.1016/j.neuro.2026.103450 · Cited by 3 · see citing works
Mechanisms of Action of Emerging Contaminants: Pharmaceuticals and Personal Care Products (PPCP)
Shi, W. F., & Tan, H. (2022) · Springer eBooks · doi:10.1007/978-981-16-9116-4_11 · Cited by 3 · see citing works
Effects of maternal LPS and developmental exposure to an environmentally relevant phthalate mixture on neuron number in the rat medial prefrontal cortex
Riesgo, V. R., Sellinger, E. P., Brinks, A. S., Juraska, J. M., & Willing, J. (2024) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2024.107370 · Cited by 2 · see citing works
Self-citation
Tyrosine hydroxylase expression and neuronal loss in the male and female adolescent ventral tegmental area
Riesgo, V. R., Zumaski, T., & Willing, J. (2024) · Neuroscience Letters · doi:10.1016/j.neulet.2024.137961 · Cited by 2 · see citing works
“These procedures for calculating cell densities were identical to those described in previous work [5,26].”
Self-citation
One year respiratory and neurodevelopmental outcome of premature neonates after exposure to plasticizers in the neonatal intensive care unit – A prospective cohort study
Panneel, L., Cleys, P., Bamai, Y. A., Wispelaere, L. D., Laroche, S. M., Hoorenbeeck, K. V., Verhulst, S. L., Covaci, A., Mulder, A., & Jorens, P. G. (2025) · Environmental Research · doi:10.1016/j.envres.2025.121266 · Cited by 2 · see citing works
Prenatal environmental risk for adolescent attention, thought, and substance use problems: A mixtures approach to coexposure and psychiatric comorbidities
Benavides, J., Cohen, J. W., Chillrud, L., Cohen, G., DeSerisy, M. L., Ramphal, B., Goldsmith, J., Kioumourtzoglou, M., & Margolis, A. E. (2025) · Environmental Epidemiology · doi:10.1097/ee9.0000000000000417 · Cited by 1 · see citing works
Learning and memory performance in a rat model of perigestational opioid exposure
Vogt, M. E., & Murphy, A. Z. (2026) · Psychopharmacology · doi:10.1007/s00213-026-07160-2 · Cited by 1 · see citing works
Prenatal exposure to di(2-ethylhexyl) phthalate alters the association of glutamatergic proteins with PTEN in the hippocampus of male rat offspring
Kiknadze, N., Zhuravliova, E., & Mikeladze, D. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.12.005 · Cited by 1 · see citing works
“The effects of phthalates on learning, memory, and related hippocampal processes have been thoroughly researched (Kougias et al., 2018; Lv et al., 2022; Safarpour et al., 2021).”
Effects of microplastics and nanoplastics on the brain and behavior: Evidence from rodent and human studies
Fattore, L., Renoir, T., Hannan, A. J., Siwach, A., Nasr, F. E., Zaky, A., Giovanni, G. D., & Landry, M. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106946 · Cited by 2 · see citing works
Effects of phthalates, environmental endocrine disrupting chemicals, on the neurovascular unit in adult male mouse
Ahmadpour, D. (2021) · theses.fr (ABES) · doi:10.70675/cf02a85cz66d4z4c79za98czb8e4497ad04c · Cited by 1 · see citing works
Developmental neurocognitive and neuropsychiatric consequences of chemical exposure amongst children in South Korea
Jang, Y., Hong, Y., & Lee, N. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819749-3.00003-8
Effects of Lactational Exposure to Endocrine Disrupting Chemicals Including Per- and Polyfluoroalkyl Substances on Maternal Postpartum Depression and Infant Neurodevelopment: Mother-Infant Pairs Cohort Study of KoreaPreprint
Kim, J. H., Moon, N., Ji, E., & Moon, H. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4171440
Fragrance Emissions into the Air and Their Impact on Air Quality and Human Health
Balcı, E., & Sofuoǧlu, A. (2023) · The handbook of environmental chemistry · doi:10.1007/698_2023_998
Region- and age-specific effects of perinatal phthalate exposure on developmental cell death and adult anatomy of dorsal and ventral hippocampus and associated cognitive behaviors
Sellinger, E. P., Brinks, A. S., Javeri, R., Theurer, S. L., Wang, R., & Juraska, J. M. (2023) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2023.107288
Self-citation
Plasma phthalate levels in children with speech delay
Artunç, N. Y., Yirün, A., Yıldıztekin, G., Erkekoğlu, P., Akkuş, P. Z., Bahadur, E. İ., Özdemir, G., & Özmert, E. N. (2025) · Toxicology Reports · doi:10.1016/j.toxrep.2025.102052
Neuroprogramming of prenatal phthalate exposures on fluid cognition: A latent variable modeling approach to quantify exposure burden and integrate neurobehavioral data
Lane, J. M., Cohen, N., Midya, V., Alcala, C. S., Eggers, S. I., Martínez-Medina, S., Valvi, D., Téllez‐Rojo, M. M., Cory‐Slechta, D. A., Wright, R. O., et al. (2025) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2025.107575
The rising tide of plastic pollutants: implications for schizophrenia onset, a mini-review
Gogos, A., Bjorksten, A., Boon, W. C., & Ponsonby, A. (2026) · Reviews on Environmental Health · doi:10.1515/reveh-2025-0106
“Perinatal phthalate exposure of rats reduced neuron number, synapse number and volume of the medial prefrontal cortex, with synapse number being positively correlated with cognitive ﬂ exibility [80].”
Effets de l’exposition aux phtalates sur les comportements de reproduction de la souris femelle
Adam, N. (2022) · theses.fr (ABES) · doi:10.70675/f8535eb9z782dz40b8zb1d0z583132d3fd1b
Adolescent blue light exposure reduces exploratory behavior and recognition memory in male and female Long Evans rats
Meszaros, D., Riesgo, V. R., & Willing, J. (2026) · Hormones and Behavior · doi:10.1016/j.yhbeh.2026.105932
Self-citation
Prenatal and childhood exposure to common plasticizers and risk-taking behavior in young adolescents
Meerts, L., Ghassabian, A., Liu, M., Trasande, L., Tiemeier, H. W., White, T., & Marroun, H. E. (2026) · Environmental Research · doi:10.1016/j.envres.2026.125140
Sex-dependent vulnerability to early-life phthalates exposure and autism spectrum disorders: a systematic review
Bucaro, I., Palanza, P., & Ponzi, D. (2026) · Frontiers in Child and Adolescent Psychiatry · doi:10.3389/frcha.2026.1865057
Perinatal exposure to the environmental pollutant butyl benzyl phthalate (BBP) induces sex-specific alterations in the neuro-immune-endocrine network in adult rats
Ruiz-Antonio, D. L., Castro, K. E. N., Garay-Canales, C. A., Rodríguez-Santiago, Y., Ríos-Avila, M. D. S., Zavala-López, C. A., Pavón, L., Pérez‐Sánchez, G., Diaz, L., & Morales‐Montor, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1838242
“Perinatal exposure to phthalates leads to molecular, structural, and behavioral alterations, including a reduction in the number of neurons and synapses as well as an increase in the size of the medial prefrontal cortex in correlation with a de ﬁ cit in cognitive ﬂ exibility (70).”
Subchronic diethyl phthalate exposure aggravates Alzheimer-like phenotypes in 5XFAD mice: Partial attenuation by Akt activation
Zhao, J., Zhang, S., Gao, D., Xie, L., Wang, Y., & Peng, D. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.112116

Behavioral effects in adult rats exposed to low doses of a phthalate mixture during the perinatal or adolescent period
Sellinger, E. P., Kougias, D. G., Drzewiecki, C. M., & Juraska, J. M. (2020) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2020.106886 · Cited by 23 · see citing works
Self-citation
Perinatal phthalate exposure increases developmental apoptosis in the rat medial prefrontal cortex
Sellinger, E. P., Riesgo, V. R., Brinks, A. S., Willing, J., & Juraska, J. M. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.09.007 · Cited by 16 · see citing works
Self-citation
Region- and age-specific effects of perinatal phthalate exposure on developmental cell death and adult anatomy of dorsal and ventral hippocampus and associated cognitive behaviors
Sellinger, E. P., Brinks, A. S., Javeri, R., Theurer, S. L., Wang, R., & Juraska, J. M. (2023) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2023.107288
Self-citation
Effects of maternal LPS and developmental exposure to an environmentally relevant phthalate mixture on neuron number in the rat medial prefrontal cortex
Riesgo, V. R., Sellinger, E. P., Brinks, A. S., Juraska, J. M., & Willing, J. (2024) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2024.107370 · Cited by 2 · see citing works
Self-citation
Exposure to endocrine-disrupting chemicals during periods of development: The effects of phthalates on the structure of the rat medial prefrontal cortex and hippocampus and associated cognitive behaviors
Sellinger, E. P. (2023) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Self-citation

Authors: Kougias, D. G., Sellinger, E. P., Willing, J., & Juraska, J. M.
Affiliations: University of Illinois Urbana-Champaign (US)
ORCID: Kougias, Daniel G.
Sellinger, Elli P.
Willing, Jari
Juraska, Janice M.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2018-07-16
Volume: 38
Issue: 31
Pages: 6864-6872
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0607-18.2018
PMC: PMC6070669
OpenAlex: W2883382216
Cited by: 72
References: 65
Citations by year: 2026: 9 · 2025: 7 · 2024: 8 · 2023: 14 · 2022: 10 · 2021: 11 · 2020: 9 · 2019: 4
FWCI: 2.95
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Environmental Protection Agency (83543401)
University of Illinois at Urbana-Champaign
National Institute of Environmental Health Sciences (P01ES022848, T32ES007326)
Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign
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 › Sexual Differentiation and Disorders
Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Keywords: phthalates, endocrine disruptors, perinatal exposure, medial prefrontal cortex, cognitive flexibility, set-shifting, synapse number, neuron number, brain development, prenatal exposure, lactation, sex differences, executive function, neuropsychiatric disorders
MeSH terms: Adult, Animals, Cell Count, Cognition Disorders, Environmental Pollutants, Female, Humans, Male, Neurons, Phthalic Acids, Pregnancy, Prenatal Exposure Delayed Effects, Set, Psychology, Synapses, Prefrontal Cortex, Rats, Long-Evans, Rats, 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

Perinatal Exposure to an Environmentally Relevant Mixture of Phthalates Results in a Lower Number of Neurons and Synapses in the Medial Prefrontal Cortex and Decreased Cognitive Flexibility in Adult Male and Female Rats

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks