Multi- and Transgenerational Outcomes of an Exposure to a Mixture of Endocrine-Disrupting Chemicals (EDCs) on Puberty and Maternal Behavior in the Female Rat.
López-Rodríguez, David; Aylwin, Carlos Francisco; Delli, Virginiaet al.
2021 • In Environmental Health Perspectives, 129 (8), p. 87003
Multi- and transgenerational outcomes of an exposure to a mixture of endocrine-disrupting chemicals on puberty and maternal behavior in the female rat.pdf
[en] BACKGROUND: The effects of endocrine-disrupting chemicals (EDCs) on fertility and reproductive development represent a rising concern in modern societies. Although the neuroendocrine control of sexual maturation is a major target of EDCs, little is known about the potential role of the hypothalamus in puberty and ovulation disruption transmitted across generations. OBJECTIVES: We hypothesized that developmental exposure to an environmentally relevant dose of EDC mixture could induce multi- and/or transgenerational alterations of sexual maturation and maternal care in female rats through epigenetic reprograming of the hypothalamus. We investigated the transmission of a disrupted reproductive phenotype via the maternal germline or via nongenomic mechanisms involving maternal care. METHODS: Adult female Wistar rats were exposed prior to and during gestation and until the end of lactation to a mixture of the following 13 EDCs: di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), bisphenol A (BPA), vinclozolin, prochloraz, procymidone, linuron, epoxynaxole, dichlorodiphenyldichloroethylene, octyl methoxynimmate, 4-methylbenzylidene camphor (4-MBC), butylparaben, and acetaminophen. Perinatally exposed offspring (F1) were mated with unexposed males to generate germ cell (F2) and transgenerationally exposed (F3 and F4) females. Sexual maturation, maternal behavior, and hypothalamic targets of exposure were studied across generations. RESULTS: Germ cell (F2) and transgenerationally (F3) EDC-exposed females, but not F1, displayed delayed pubertal onset and altered folliculogenesis. We reported a transgenerational alteration of key hypothalamic genes controlling puberty and ovulation (Kiss1, Esr1, and Oxt), and we identified the hypothalamic polycomb group of epigenetic repressors as actors of this mechanism. Furthermore, we found a multigenerational reduction of maternal behavior (F1-F3) induced by a loss in hypothalamic dopaminergic signaling. Using a cross-fostering paradigm, we identified that the reduction in maternal phenotype was normalized in EDC-exposed pups raised by unexposed dams, but no reversal of the pubertal phenotype was achieved. DISCUSSION: Rats developmentally exposed to an EDC mixture exhibited multi- and transgenerational disruption of sexual maturation and maternal care via hypothalamic epigenetic reprogramming. These results raise concerns about the impact of EDC mixtures on future generations. https://doi.org/10.1289/EHP8795.
Disciplines :
Pediatrics Endocrinology, metabolism & nutrition
Author, co-author :
López-Rodríguez, David ; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium.
Aylwin, Carlos Francisco; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &
Delli, Virginia
Sevrin, Elena ; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium.
Campanile, Marzia; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium.
Martin, Marion; Lille Neuroscience & Cognition (LilNCog), Institut national de la santé et de la
Franssen, Delphine ; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium.
Gérard, Arlette ; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium.
Blacher, Silvia ; Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
Tirelli, Ezio ; Department of Psychology: Cognition and Behavior, University of Liège, Liège,
Noël, Agnès ; Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium.
Lomniczi, Alejandro; Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &
PARENT, Anne-Simone ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie
Multi- and Transgenerational Outcomes of an Exposure to a Mixture of Endocrine-Disrupting Chemicals (EDCs) on Puberty and Maternal Behavior in the Female Rat.
Publication date :
August 2021
Journal title :
Environmental Health Perspectives
ISSN :
0091-6765
Publisher :
U.S. Department of Health and Human Services, Pk
Volume :
129
Issue :
8
Pages :
87003
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
P51 OD011092/OD/NIH HHS/United States; R01 HD084542/HD/NICHD NIH HHS/United States
Adewale HB, Jefferson WN, Newbold RR, Patisaul HB. 2009. Neonatal bisphenol-A exposure alters rat reproductive development and ovarian morphology without impairing activation of gonadotropin-releasing hormone neurons. Biol Reprod81(4):690–699, PMID: 19535786, 10.1095/biolreprod.109.078261.
Aksglaede L, Sørensen K, Petersen JH, Skakkebaek NE, Juul A. 2009. Recent decline in age at breast development: The Copenhagen Puberty Study. Pediatrics123(5):e932–e939, PMID: 19403485, 10.1542/peds.2008-2491.
Arambula SE, Belcher SM, Planchart A, Turner SD, Patisaul HB. 2016. Impact of low dose oral exposure to bisphenol A (BPA) on the neonatal rat hypothalamic and hippocampal transcriptome: A CLARITY-BPA Consortium study. Endocrinology157(10):3856–3872, PMID: 27571134, 10.1210/en.2016-1339.
Axelstad M, Christiansen S, Boberg J, Scholze M, Jacobsen PR, Isling LK, et al.2014. Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats. Reproduction147(4):489–501, PMID: 24298046, 10.1530/REP-13-0447.
Berger A, Ziv-Gal A, Cudiamat J, Wang W, Zhou C, Flaws JA. 2016. The effects of in utero bisphenol A exposure on the ovaries in multiple generations of mice. Reprod Toxicol60:39–52, PMID: 26746108, 10.1016/j.reprotox.2015.12.004.
Bergman A, Heindel JJ, Kasten T, Kidd KA, Jobling S, Neira M, et al.2013. The impact of endocrine disruption: A consensus statement on the state of the science. Environ Health Perspect121(4):A104–A106, PMID: 23548368, 10.1289/ehp.1205448.
Biro FM, Galvez MP, Greenspan LC, Succop PA, Vangeepuram N, Pinney SM, et al.2010. Pubertal assessment method and baseline characteristics in a mixed longitudinal study of girls. Pediatrics126(3):e583–e590, 10.1542/peds.2009-3079.
Boudalia S, Berges R, Chabanet C, Folia M, Decocq L, Pasquis B, et al.2014. A multi-generational study on low-dose BPA exposure in Wistar rats: Effects on maternal behavior, flavor intake and development. Neurotoxicol Teratol41:16–26, PMID: 24269606, 10.1016/j.ntt.2013.11.002.
Bourguignon JP, Franchimont P. 1984. Puberty-related increase in LHRH release from rat hypothalamus in vitro. Endocrinology114(5):1941–1943, PMID: 6370671, 10.1210/endo-114-5-1941.
Bourguignon JP, Gerard A, Franchimont P. 1989a. Direct activation of gonadotropin-releasing hormone secretion through different receptors to neuroexcitatory amino acids. Neuroendocrinology49(4):402–408, PMID: 2541362, 10.1159/000125145.
Bourguignon JP, Gerard A, Mathieu J, Simons J, Franchimont P. 1989b. Pulsatile release of gonadotropin-releasing hormone from hypothalamic explants is restrained by blockade of N-methyl-D,L-aspartate receptors. Endocrinology125(2):1090–1096, PMID: 2546737, 10.1210/endo-125-2-1090.
Brehm E, Flaws JA. 2019. Transgenerational effects of endocrine-disrupting chemicals on male and female reproduction. Endocrinology160(6):1421–1435, PMID: 30998239, 10.1210/en.2019-00034.
Brehm E, Rattan S, Gao L, Flaws JA. 2018. Prenatal exposure to di(2-ethylhexyl) phthalate causes long-term transgenerational effects on female reproduction in mice. Endocrinology159(2):795–809, PMID: 29228129, 10.1210/en.2017-03004.
Cabaton NJ, Wadia PR, Rubin BS, Zalko D, Schaeberle CM, Askenase MH, et al.2011. Perinatal exposure to environmentally relevant levels of bisphenol A decreases fertility and fecundity in CD-1 mice. Environ Health Perspect119(4):547–552, PMID: 21126938, 10.1289/ehp.1002559.
Calafat AM, Ye X, Wong L-Y, Bishop AM, Needham LL. 2010. Urinary concentrations of four parabens in the U.S. population: NHANES 2005–2006. Environ Health Perspect118(5):679–685, PMID: 20056562, 10.1289/ehp.0901560.
Cameron N, Del Corpo A, Diorio J, McAllister K, Sharma S, Meaney MJ. 2008a. Maternal programming of sexual behavior and hypothalamic-pituitary-gonadal function in the female rat. PLoS One3(5):e2210, PMID: 18493313, 10.1371/journal.pone.0002210.
Cameron NM, Fish EW, Meaney MJ. 2008b. Maternal influences on the sexual behavior and reproductive success of the female rat. Horm Behav54(1):178–184, PMID: 18417127, 10.1016/j.yhbeh.2008.02.013.
Cao J, Mickens JA, McCaffrey KA, Leyrer SM, Patisaul HB. 2012. Neonatal bisphenol A exposure alters sexually dimorphic gene expression in the postnatal rat hypothalamus. Neurotoxicology33(1):23–36, PMID: 22101008, 10.1016/j.neuro.2011.11.002.
Carbone S, Szwarcfarb B, Reynoso R, Ponzo OJ, Cardoso N, Ale E, et al.2010. In vitro effect of octyl-methoxycinnamate (OMC) on the release of Gn-RH and amino acid neurotransmitters by hypothalamus of adult rats. Exp Clin Endocrinol Diabetes118(5):298–303, PMID: 20198561, 10.1055/s-0029-1224153.
Carou ME, Deguiz ML, Reynoso R, Szwarcfarb B, Carbone S, Moguilevsky JA, et al.2009. Impact of the UV-B filter 4-(methylbenzylidene)-camphor (4-MBC) during prenatal development in the neuroendocrine regulation of gonadal axis in male and female adult rats. Environ Toxicol Pharmacol27(3):410–414, PMID: 21783972, 10.1016/j.etap.2009.01.007.
Champagne FA, Curley JP. 2016. Plasticity of the maternal brain across the lifespan. New Dir Child Adolesc Dev2016(153):9–21, PMID: 27589495, 10.1002/cad.20164.
Christiansen K, Axelstad A, Boberg M, Scholze J, Jacobsen M, Faust PR, et al.2012. Mixtures of endocrine disrupting contaminants modelled on human high end exposures: An exploratory study in rats. Int J Androl35(3):303–316, PMID: 22372636, 10.1111/j.1365-2605.2011.01242.x.
Christiansen S, Boberg J, Axelstad M, Dalgaard M, Vinggaard AM, Metzdorff SB, et al.2010. Low-dose perinatal exposure to di(2-ethylhexyl) phthalate induces anti-androgenic effects in male rats. Reprod Toxicol30(2):313–321, PMID: 20420898, 10.1016/j.reprotox.2010.04.005.
Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A, et al.2009. Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ Health Perspect117(12):1839–1846, PMID: 20049201, 10.1289/ehp.0900689.
Clarkson J, Han S-K, Liu X, Lee K, Herbison AE. 2010. Neurobiological mechanisms underlying kisspeptin activation of gonadotropin-releasing hormone (GnRH) neurons at puberty. Mol Cell Endocrinol324(1–2):45–50, PMID: 20109523, 10.1016/j.mce.2010.01.026.
Clarkson J, Herbison AE. 2006. Development of GABA and glutamate signaling at the GnRH neuron in relation to puberty. Mol Cell Endocrinol254–255:32–38, 10.1016/j.mce.2006.04.036.
Collet SH, Picard-Hagen N, Viguie C, Lacroix MZ, Toutain P-L, Gayrard V. 2010. Estrogenicity of bisphenol A: A concentration-effect relationship on luteinizing hormone secretion in a sensitive model of prepubertal lamb. Toxicol Sci117(1):54–62, PMID: 20566471, 10.1093/toxsci/kfq186.
Cousins IT, Staples CA, Kleĉka GM, Mackay D. 2002. A multimedia assessment of the environmental fate of bisphenol A. Hum Ecol Risk Assess8(5):1107–1135, 10.1080/1080-700291905846.
de Castro VLSS, Maia AH. 2012. Prenatal epoxiconazole exposure effects on rat postnatal development. Birth Defects Res B Dev Reprod Toxicol95(2):123–129, PMID: 22140080, 10.1002/bdrb.20345.
Dean A, van den Driesche S, Wang Y, McKinnell C, Macpherson S, Eddie SL, et al.2016. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences. Sci Rep6:19789, PMID: 26813099, 10.1038/srep19789.
Demeneix B, Slama R. 2019. Endocrine Disruptors: From Scientific Evidence to Human Health Protection. Brussels, Belgium: European Parliament Policy Department for Citizens’ Rights and Constitutional Affairs. https://www.europarl.europa.eu/RegData/etudes/STUD/2019/608866/IPOL_STU(2019)608866_EN.pdf [accessed 16 May 2020].
Drobna Z, Henriksen AD, Wolstenholme JT, Montiel C, Lambeth PS, Shang S, et al.2018. Transgenerational effects of bisphenol A on gene expression and DNA methylation of imprinted genes in brain. Endocrinology159(1):132–144, PMID: 29165653, 10.1210/en.2017-00730.
Durrer S, Ehnes C, Fuetsch M, Maerkel K, Schlumpf M, Lichtensteiger W. 2007. Estrogen sensitivity of target genes and expression of nuclear receptor co-regulators in rat prostate after pre- and postnatal exposure to the ultraviolet filter 4-methylbenzylidene camphor. Environ Health Perspect115(suppl 1):42–50, PMID: 18174949, 10.1289/ehp.9134.
EFSA (European Food Safety Authority).2019. Endocrine Disruptors. An Overview of Latest Developments at European Level in the Context of Plant Protection Products. https://www.europarl.europa.eu/RegData/etudes/STUD/2019/631743/EPRS_STU(2019)631743_EN.pdf.
Faass O, Schlumpf M, Reolon S, Henseler M, Maerkel K, Durrer S, et al.2009. Female sexual behavior, estrous cycle and gene expression in sexually dimorphic brain regions after pre- and postnatal exposure to endocrine active UV filters. Neurotoxicology30(2):249–260, PMID: 19150460, 10.1016/j.neuro.2008.12.008.
Fang Y-Y, Yamaguchi T, Song SC, Tritsch NX, Lin D. 2018. A hypothalamic midbrain pathway essential for driving maternal behaviors. Neuron98(1):192–207, PMID: 29621487, 10.1016/j.neuron.2018.02.019.
Fernandez M, Bianchi M, Lux-Lantos V, Libertun C, Fernández M, Bianchi M, et al.2009. Neonatal exposure to bisphenol A alters reproductive parameters and gonadotropin releasing hormone signaling in female rats. Environ Health Perspect117(5):757–762, PMID: 19479018, 10.1289/ehp.0800267.
Francis D, Diorio J, Liu D, Meaney MJ. 1999. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science286(5442):1155–1158, PMID: 10550053, 10.1126/science.286.5442.1155.
Franssen D, Gérard A, Hennuy B, Donneau AF, Bourguignon JP, Parent AS. 2016. Delayed neuroendocrine sexual maturation in female rats after a very low dose of bisphenol A through altered GABAergic neurotransmission and opposing effects of a high dose. Endocrinology157(5):1740–1750, PMID: 26950200, 10.1210/en.2015-1937.
Franssen D, Ioannou YS, Alvarez-Real A, Gérard A, Mueller JK, Heger S, et al.2014. Pubertal timing after neonatal diethylstilbestrol exposure in female rats: Neuroendocrine vs peripheral effects and additive role of prenatal food restriction. Reprod Toxicol44(0):63–72, PMID: 24316331, 10.1016/j.reprotox.2013.10.006.
Gao N, Hu R, Huang Y, Dao L, Zhang C, Liu Y, et al.2018. Specific effects of prenatal DEHP exposure on neuroendocrine gene expression in the developing hypothalamus of male rats. Arch Toxicol92(1):501–512, PMID: 28871463, 10.1007/s00204-017-2049-z.
Gillette R, Miller-Crews I, Skinner MK, Crews D. 2015. Distinct actions of ancestral vinclozolin and juvenile stress on neural gene expression in the male rat. Front Genet6:56, PMID: 25784924, 10.3389/fgene.2015.00056.
Goldman JM, Murr AS, Cooper RL. 2007. The rodent estrous cycle: Characterization of vaginal cytology and its utility in toxicological studies. Birth Defects Res B Dev Reprod Toxicol80(2):84–97, PMID: 17342777, 10.1002/bdrb.20106.
Goldsby JA, Wolstenholme JT, Rissman EF. 2017. Multi- and transgenerational consequences of bisphenol A on sexually dimorphic cell populations in mouse brain. Endocrinology158(1):21–30, PMID: 27841950, 10.1210/en.2016-1188.
Gonzales RC, Woods RE. 2008. Digital Image Processing. 3rd ed.Upper Saddle River, NJ: Prentice Hall International.
Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, et al.2015. EDC-2: The Endocrine Society’s second Scientific Statement on endocrine-disrupting chemicals. Endocr Rev36(6):E1–E150, PMID: 26544531, 10.1210/er.2015-1010.
Hannon PR, Peretz J, Flaws JA. 2014. Daily exposure to di(2-ethylhexyl) phthalate alters estrous cyclicity and accelerates primordial follicle recruitment potentially via dysregulation of the phosphatidylinositol 3-kinase signaling pathway in adult mice. Biol Reprod90(6):136, PMID: 24804967, 10.1095/biolreprod.114.119032.
Hass U, Christiansen S, Axelstad M, Scholze M, Boberg J. 2017. Combined exposure to low doses of pesticides causes decreased birth weights in rats. Reprod Toxicol72:97–105, PMID: 28526456, 10.1016/j.reprotox.2017.05.004.
Hass U, Jacobsen PR, Boberg J, Christiansen S, Nellemann C, Kristensen DM, et al.2010. Developmental exposure to paracetamol causes anti-androgenic effects in male rat offspring. Reprod Toxicol30(2):230–231, 10.1016/j.reprotox.2010.05.042.
Hass U, Scholze M, Christiansen S, Dalgaard M, Vinggaard AM, Axelstad M, et al.2007. Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. Environ Health Perspect115(suppl 1):122–128, PMID: 18174960, 10.1289/ehp.9360.
Heindel JJ, Blumberg B, Cave M, Machtinger R, Mantovani A, Mendez MA, et al.2017. Metabolism disrupting chemicals and metabolic disorders. Reprod Toxicol68:3–33, PMID: 27760374, 10.1016/j.reprotox.2016.10.001.
Hirshfield AN, Rees Midgley A Jr. 1978. Morphometric analysis of follicular development in the rat. Biol Reprod19(3):597–605, PMID: 363183, 10.1095/biolreprod19.3.597.
Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H, Iguchi T. 2002. Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction. Reprod Toxicol16(2):117–122, PMID: 11955942, 10.1016/S0890-6238(02)00006-0.
Howdeshell KL, Wilson VS, Furr J, Lambright CR, Rider CV, Blystone CR, et al.2008. A mixture of five phthalate esters inhibits fetal testicular testosterone production in the Sprague-Dawley rat in a cumulative, dose-additive manner. Toxicol Sci105(1):153–165, PMID: 18411233, 10.1093/toxsci/kfn077.
Hu J, Du G, Zhang W, Huang H, Chen D, Wu D, et al.2013. Short-term neonatal/prepubertal exposure of dibutyl phthalate (DBP) advanced pubertal timing and affected hypothalamic kisspeptin/GPR54 expression differently in female rats. Toxicology314(1):65–75, PMID: 24056307, 10.1016/j.tox.2013.09.007.
Isling LK, Boberg J, Jacobsen PR, Mandrup KR, Axelstad M, Christiansen S, et al.2014. Late-life effects on rat reproductive system after developmental exposure to mixtures of endocrine disrupters. Reproduction147(4):465–476, PMID: 24287426, 10.1530/REP-13-0448.
Jacobsen PR, Christiansen S, Boberg J, Nellemann C, Hass U. 2010. Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats. Int J Androl33(2):434–442, PMID: 20487043, 10.1111/j.1365-2605.2009.01046.x.
Johansson HKL, Jacobsen PR, Hass U, Svingen T, Vinggaard AM, Isling LK, et al.2016. Perinatal exposure to mixtures of endocrine disrupting chemicals reduces female rat follicle reserves and accelerates reproductive aging. Reprod Toxicol61:186–194, PMID: 27049580, 10.1016/j.reprotox.2016.03.045.
Kang K-S, Che J-H, Ryu D-Y, Kim T-W, Li G-X, Lee Y-S. 2002. Decreased sperm number and motile activity on the F1 offspring maternally exposed to butyl p-hydroxybenzoic acid (butyl paraben). J Vet Med Sci64(3):227–235, PMID: 11999442, 10.1292/jvms.64.227.
Kang H-S, Kyung M-S, Ko A, Park J-H, Hwang M-S, Kwon J-E, et al.2016. Urinary concentrations of parabens and their association with demographic factors: A population-based cross-sectional study. Environ Res146:245–251, PMID: 26775005, 10.1016/j.envres.2015.12.032.
Kortenkamp A. 2007. Ten years of mixing cocktails: A review of combination effects of endocrine-disrupting chemicals. Environ Health Perspect115(suppl 1):98–105, PMID: 18174957, 10.1289/ehp.9357.
Krause M, Andersson A-M, Skakkebaek NE, Frederiksen H. 2017. Exposure to UV filters during summer and winter in Danish kindergarten children. Environ Int99:177–184, PMID: 27865524, 10.1016/j.envint.2016.11.011.
Krishnan K, Rahman S, Hasbum A, Morales D, Thompson LM, Crews D, et al.2019. Maternal care modulates transgenerational effects of endocrine-disrupting chemicals on offspring pup vocalizations and adult behaviors. Horm Behav107:96–109, PMID: 30576639, 10.1016/j.yhbeh.2018.12.009.
Krueger F, Andrews SR. 2011. Bismark: A flexible aligner and methylation caller for bisulfite-seq applications. Bioinformatics27(11):1571–1572, PMID: 21493656, 10.1093/bioinformatics/btr167.
Kurian JR, Keen KL, Kenealy BP, Garcia JP, Hedman CJ, Terasawa E. 2015. Acute influences of bisphenol A exposure on hypothalamic release of gonadotropin-releasing hormone and kisspeptin in female rhesus monkeys. Endocrinology156(7):2563–2570, PMID: 25853665, 10.1210/en.2014-1634.
Laier P, Metzdorff SB, Borch J, Hagen ML, Hass U, Christiansen S, et al.2006. Mechanisms of action underlying the antiandrogenic effects of the fungicide prochloraz. Toxicol Appl Pharmacol213(2):160–171, PMID: 16375936, 10.1016/j.taap.2005.10.013.
Lee SG, Kim JY, Chung J-Y, Kim Y-J, Park J-E, Oh S, et al.2013. Bisphenol A exposure during adulthood causes augmentation of follicular atresia and luteal regression by decreasing 17β-estradiol synthesis via downregulation of aromatase in rat ovary. Environ Health Perspect121(6):663–669, PMID: 23512349, 10.1289/ehp.1205823.
Liao Y, Smyth GK, Shi W. 2019. The R package Rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Research47(8):e47, 10.1093/nar/gkz114.
Li N, Zhou L, Zhu J, Liu T, Ye L. 2020. Role of the 17β-hydroxysteroid dehydrogenase signalling pathway in di-(2-ethylhexyl) phthalate-induced ovarian dysfunction: An in vivo study. Sci Total Environ712:134406, PMID: 31927438, 10.1016/j.scitotenv.2019.134406.
Lim JP, Brunet A. 2013. Bridging the transgenerational gap with epigenetic memory. Trends Genet29(3):176–186, PMID: 23410786, 10.1016/j.tig.2012.12.008.
Liu X, Craig ZR. 2019. Environmentally relevant exposure to dibutyl phthalate disrupts DNA damage repair gene expression in the mouse ovary†. Biol Reprod101(4):854–867, PMID: 31318015, 10.1093/biolre/ioz122.
Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, et al.1997. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science277(5332):1659–1662, PMID: 9287218, 10.1126/science.277.5332.1659.
Liu W, Yang Y, Shao M, Duan P, Li L, Zhu M, et al.2018. Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats. Iran J Basic Med Sci21(8):848–855, PMID: 30186573, 10.22038/IJBMS.2018.28489.6905.
Loganathan N, McIlwraith EK, Belsham DD. 2021. Bisphenol A induces Agrp gene expression in hypothalamic neurons through a mechanism involving ATF3. Neuroendocrinology111(7):678–695, PMID: 32575098, 10.1159/000509592.
Lomniczi A, Loche A, Castellano JM, Ronnekleiv OK, Bosch M, Kaidar G, et al.2013. Epigenetic control of female puberty. Nat Neurosci16(3):281–289, PMID: 23354331, 10.1038/nn.3319.
Lonstein JS, Pereira M, Morrell JI, Marler C. A.2015. Parenting Behavior. In: Knobil and Neill’s Physiology of Reproduction. Plant TM, Zeleznik AJ, eds. 4th ed. London, UK: Academic Press.
Lopez-Rodriguez D, Franssen D, Bakker J, Lomniczi A, Parent A-S. 2021. Cellular and molecular features of EDC exposure: Consequences for the GnRH network. Nat Rev Endocrinol17(2):83–96, PMID: 33288917, 10.1038/s41574-020-00436-3.
López-Rodríguez D, Franssen D, Sevrin E, Gerard A, Balsat C, Blacher S, et al.2019. Persistent vs transient alteration of folliculogenesis and estrous cycle after neonatal vs adult exposure to bisphenol A. Endocrinology160(11):2558–2572, PMID: 31503316, 10.1210/en.2019-00505.
Losa SM, Todd KL, Sullivan AW, Cao J, Mickens JA, Patisaul HB. 2011. Neonatal exposure to genistein adversely impacts the ontogeny of hypothalamic kisspeptin signaling pathways and ovarian development in the peripubertal female rat. Reprod Toxicol31(3):280–289, PMID: 20951797, 10.1016/j.reprotox.2010.10.002.
Losa-Ward SM, Todd KL, McCaffrey KA, Tsutsui K, Patisaul HB. 2012. Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A. Biol Reprod87(2):28–21-9, PMID: 22572997, 10.1095/biolreprod.112.100826.
Ma M, Kondo T, Ban S, Umemura T, Kurahashi N, Takeda M, et al.2006. Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions. Toxicol Sci93(1):164–171, PMID: 16763069, 10.1093/toxsci/kfl036.
Maerkel K, Durrer S, Henseler M, Schlumpf M, Lichtensteiger W. 2007. Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: Developmental exposure of rats to 4-methylbenzylidene camphor. Toxicol Appl Pharmacol218(2):152–165, PMID: 17188730, 10.1016/j.taap.2006.10.026.
Mahalingam S, Ther L, Gao L, Wang W, Ziv-Gal A, Flaws JA. 2017. The effects of in utero bisphenol A exposure on ovarian follicle numbers and steroidogenesis in the F1 and F2 generations of mice. Reprod Toxicol74:150–157, PMID: 28970132, 10.1016/j.reprotox.2017.09.013.
Mahoney MM, Padmanabhan V. 2010. Developmental programming: Impact of fetal exposure to endocrine-disrupting chemicals on gonadotropin-releasing hormone and estrogen receptor mRNA in sheep hypothalamus. Toxicol Appl Pharmacol247(2):98–104, PMID: 20621667, 10.1016/j.taap.2010.05.017.
Mandrup KR, Johansson HKL, Boberg J, Pedersen AS, Mortensen MS, Jorgensen JS, et al.2015. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats. Reprod Toxicol54:47–57, PMID: 25305543, 10.1016/j.reprotox.2014.09.016.
Manikkam M, Guerrero-Bosagna C, Tracey R, Haque MM, Skinner MK. 2012a. Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PLoS One7(2):e31901, PMID: 22389676, 10.1371/journal.pone.0031901.
Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK. 2012b. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS One7(9):e46249, PMID: 23049995, 10.1371/journal.pone.0046249.
Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK. 2013. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One8(1):e55387, PMID: 23359474, 10.1371/journal.pone.0055387.
Matagne V, Rasier G, Lebrethon M-C, Gérard A, Bourguignon J-P. 2004. Estradiol stimulation of pulsatile gonadotropin-releasing hormone secretion in vitro: Correlation with perinatal exposure to sex steroids and induction of sexual precocity in vivo. Endocrinology145(6):2775–2783, PMID: 14988382, 10.1210/en.2003-1259.
McIntyre BS, Barlow NJ, Foster PM. 2001. Androgen-mediated development in male rat offspring exposed to flutamide in utero: Permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues. Toxicol Sci62(2):236–249, PMID: 11452136, 10.1093/toxsci/62.2.236.
Mendoza-Rodríguez CA, García-Guzmán M, Baranda-Avila N, Morimoto S, Perrot-Applanat M, Cerbón M. 2011. Administration of bisphenol A to dams during perinatal period modifies molecular and morphological reproductive parameters of the offspring. Reprod Toxicol31(2):177–183, PMID: 21055461, 10.1016/j.reprotox.2010.10.013.
Monje L, Varayoud J, Luque EH, Ramos JG. 2007. Neonatal exposure to bisphenol a modifies the abundance of estrogen receptor alpha transcripts with alternative 5′-untranslated regions in the female rat preoptic area. J Endocrinol194(1):201–212, PMID: 17592034, 10.1677/JOE-07-0014.
Monje L, Varayoud J, Munoz-de-Toro M, Luque EH, Ramos JG. 2009. Neonatal exposure to bisphenol A alters estrogen-dependent mechanisms governing sexual behavior in the adult female rat. Reprod Toxicol28(4):435–442, PMID: 19577632, 10.1016/j.reprotox.2009.06.012.
Monje L, Varayoud J, Munoz-de-Toro M, Luque EH, Ramos JG. 2010. Exposure of neonatal female rats to bisphenol A disrupts hypothalamic LHRH pre-mRNA processing and estrogen receptor alpha expression in nuclei controlling estrous cyclicity. Reprod Toxicol30(4):625–634, PMID: 20951796, 10.1016/j.reprotox.2010.08.004.
Moore-Ambriz TR, Acuña-Hernández DG, Ramos-Robles B, Sánchez-Gutiérrez M, Santacruz-Márquez R, Sierra-Santoyo A, et al.2015. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes. Toxicol Appl Pharmacol289(3):507–514, PMID: 26493930, 10.1016/j.taap.2015.10.010.
Mueller JK, Dietzel A, Lomniczi A, Loche A, Tefs K, Kiess W, et al.2011. Transcriptional regulation of the human KiSS1 gene. Mol Cell Endocrinol342(1–2):8–19, PMID: 21672609, 10.1016/j.mce.2011.04.025.
Murawski A, Schmied-Tobies MIH, Rucic E, Schmidtkunz C, Küpper K, Leng G, et al.2021. Metabolites of 4-methylbenzylidene camphor (4-MBC), butylated hydroxytoluene (BHT), and tris(2-ethylhexyl) trimellitate (TOTM) in urine of children and adolescents in Germany – human biomonitoring results of the German Environmental Survey GerES V (2014–2017. Environ Res192:110345, PMID: 33096061, 10.1016/j.envres.2020.110345.
Mylchreest E, Wallace DG, Cattley RC, Foster PM. 2000. Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation. Toxicol Sci55(1):143–151, PMID: 10788569, 10.1093/toxsci/55.1.143.
Nah WH, Park MJ, Gye MC. 2011. Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice. Clin Exp Reprod Med38(2):75–81, PMID: 22384422, 10.5653/cerm.2011.38.2.75.
Naulé L, Picot M, Martini M, Parmentier C, Hardin-Pouzet H, Keller M, et al.2014. Neuroendocrine and behavioral effects of maternal exposure to oral bisphenol A in female mice. J Endocrinol220(3):375–388, PMID: 24403293, 10.1530/JOE-13-0607.
Niermann S, Rattan S, Brehm E, Flaws JA. 2015. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice. Reprod Toxicol53:23–32, PMID: 25765777, 10.1016/j.reprotox.2015.02.013.
Nikaido Y, Danbara N, Tsujita-Kyutoku M, Yuri T, Uehara N, Tsubura A. 2005. Effects of prepubertal exposure to xenoestrogen on development of estrogen target organs in female CD-1 mice. In Vivo19(3):487–494, PMID: 15875766. Medline,
Nikaido Y, Yoshizawa K, Danbara N, Tsujita-Kyutoku M, Yuri T, Uehara N, et al.2004. Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring. Reprod Toxicol18(6):803–811, PMID: 15279878, 10.1016/j.reprotox.2004.05.002.
Nilsson E, King SE, McBirney M, Kubsad D, Pappalardo M, Beck D, et al.2018. Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases. PLoS One13(8):e0202662, PMID: 30157260, 10.1371/journal.pone.0202662.
Nilsson E, Larsen G, Manikkam M, Guerrero-Bosagna C, Savenkova MI, Skinner MK. 2012. Environmentally induced epigenetic transgenerational inheritance of ovarian disease. PLoS One7(5):e36129, PMID: 22570695, 10.1371/journal.pone.0036129.
Nolwenn A, Brusamonti L, Mhaouty-Kodja S. 2021. Exposure of adult female mice to low doses of di(2-ethylhexyl) phthalate alone or in an environmental phthalate mixture: Evaluation of reproductive behavior and underlying neural mechanisms. Environ Health Perspect129(1):17008, PMID: 33502250, 10.1289/EHP7662.
Ojeda SR, Prevot V, Heger S, Lomniczi A, Dziedzic B, Mungenast A. 2003. Glia-to-neuron signaling and the neuroendocrine control of female puberty. Ann Med35(4):244–255, PMID: 12846266, 10.1080/07853890310005164.
Ojeda Skinner MK.2006. Chapter 38. Puberty in the rat. In: Knobil and Neill’s Physiology of Reproduction, vol. 2. Knobil E, Neill JD, eds. Oxford, UK: Gulf Professional Publishing, 2061–2103.
Otsu N. 1979. A threshold selection method from gray-level histograms. IEEE Trans Syst, Man, Cybern9(1):62–66, 10.1109/TSMC.1979.4310076.
Parent A-S, Franssen D, Fudvoye J, Gérard A, Bourguignon J-P. 2015. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents. Front Neuroendocrinol38:12–36, PMID: 25592640, 10.1016/j.yfrne.2014.12.004.
Parent AS, Lebrethon MC, Gérard A, Vandersmissen E, Bourguignon JP. 2000. Leptin effects on pulsatile gonadotropin releasing hormone secretion from the adult rat hypothalamus and interaction with cocaine and amphetamine regulated transcript peptide and neuropeptide Y. Regul Pept92(1–3):17–24, PMID: 11024560, 10.1016/S0167-0115(00)00144-0.
Parent AS, Rasier G, Matagne V, Lomniczi A, Lebrethon MC, Gérard A. 2008. Oxytocin facilitates female sexual maturation through a gliatoneuron signaling pathway. Endocrinology149(3):1358–1365, 10.1210/en.2007-1054.
Parent A-S, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon J-P. 2003. The timing of normal puberty and the age limits of sexual precocity: Variations around the world, secular trends, and changes after migration. Endocr Rev24(5):668–693, PMID: 14570750, 10.1210/er.2002-0019.
Patel S, Brehm E, Gao L, Rattan S, Ziv-Gal A, Flaws JA. 2017. Bisphenol a exposure, ovarian follicle numbers, and female sex steroid hormone levels: Results from a CLARITY-BPA study. Endocrinology158(6):1727–1738, PMID: 28324068, 10.1210/en.2016-1887.
Peña CJ, Neugut YD, Champagne FA. 2013. Developmental timing of the effects of maternal care on gene expression and epigenetic regulation of hormone receptor levels in female rats. Endocrinology154(11):4340–4351, PMID: 24002038, 10.1210/en.2013-1595.
Peters H. 1969. The development of the mouse ovary from birth to maturity. Acta Endocrinol (Copenh)62(1):98–116, PMID: 5394354, 10.1530/acta.0.0620098.
Petro EML, D’Hollander W, Covaci A, Bervoets L, Fransen E, De Neubourg D, et al.2014. Perfluoroalkyl acid contamination of follicular fluid and its consequence for in vitro oocyte developmental competence. Sci Total Environ496:282–288, PMID: 25089690, 10.1016/j.scitotenv.2014.07.028.
Petro EML, Leroy JLMR, Covaci A, Fransen E, De Neubourg D, Dirtu AC, et al.2012. Endocrine-disrupting chemicals in human follicular fluid impair in vitro oocyte developmental competence. Hum Reprod27(4):1025–1033, PMID: 22267834, 10.1093/humrep/der448.
Pfaffl MW. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research29(9):e45, PMID: 11328886, 10.1093/nar/29.9.e45.
Pocar P, Fiandanese N, Berrini A, Secchi C, Borromeo V. 2017. Maternal exposure to di(2-ethylhexyl)phthalate (DEHP) promotes the transgenerational inheritance of adult-onset reproductive dysfunctions through the female germline in mice. Toxicol Appl Pharmacol322:113–121, PMID: 28286118, 10.1016/j.taap.2017.03.008.
Rasier G, Parent A-S, Gérard A, Denooz R, Lebrethon M-C, Charlier C, et al.2008. Mechanisms of interaction of endocrine-disrupting chemicals with glutamate-evoked secretion of gonadotropin-releasing hormone. Toxicol Sci102(1):33–41, PMID: 18032409, 10.1093/toxsci/kfm285.
Rasier G, Parent A-S, Gérard A, Lebrethon M-C, Bourguignon J-P. 2007. Early maturation of gonadotropin-releasing hormone secretion and sexual precocity after exposure of infant female rats to estradiol or dichlorodiphenyltrichloroethane. Biol Reprod77(4):734–742, PMID: 17596564, 10.1095/biolreprod.106.059303.
Rattan S, Beers HK, Kannan A, Ramakrishnan A, Brehm E, Bagchi I, et al.2019. Prenatal and ancestral exposure to di(2-ethylhexyl) phthalate alters gene expression and DNA methylation in mouse ovaries. Toxicol Appl Pharmacol379:114629, PMID: 31211961, 10.1016/j.taap.2019.114629.
Rattan S, Brehm E, Gao L, Flaws JA. 2018a. Di(2-ethylhexyl) phthalate exposure during prenatal development causes adverse transgenerational effects on female fertility in mice. Toxicol Sci163(2):420–429, PMID: 29471507, 10.1093/toxsci/kfy042.
Rattan S, Brehm E, Gao L, Niermann S, Flaws JA. 2018b. Prenatal exposure to di(2-ethylhexyl) phthalate disrupts ovarian function in a transgenerational manner in female mice. Biol Reprod98(1):130–145, PMID: 29165555, 10.1093/biolre/iox154.
Rebuli ME, Cao J, Sluzas E, Delclos KB, Camacho L, Lewis SM, et al.2014. Investigation of the effects of subchronic low dose oral exposure to bisphenol A (BPA) and ethinyl estradiol (EE) on estrogen receptor expression in the juvenile and adult female rat hypothalamus. Toxicol Sci140(1):190–203, PMID: 24752507, 10.1093/toxsci/kfu074.
Roa J, Herbison AE. 2012. Direct regulation of GnRH neuron excitability by arcuate nucleus POMC and NPY neuron neuropeptides in female mice. Endocrinology153(11):5587–5599, PMID: 22948210, 10.1210/en.2012-1470.
Robinson MD, McCarthy DJ, Smyth GK. 2010. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics26(1):139–140, 10.1093/bioinformatics/btp616.
Rodríguez HA, Santambrosio N, Santamaría CG, Muñoz-de-Toro M, Luque EH. 2010. Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reprod Toxicol30(4):550–557, PMID: 20692330, 10.1016/j.reprotox.2010.07.008.
Ruiz-Pino F, Miceli D, Franssen D, Vazquez MJ, Farinetti A, Castellano JM, et al.2019. Environmentally relevant perinatal exposures to bisphenol a disrupt postnatal Kiss1/NKB neuronal maturation and puberty onset in female mice. Environ Health Perspect127(10):107011, PMID: 31652106, 10.1289/EHP5570.
Salazar V, Castillo C, Ariznavarreta C, Campón R, Tresguerres JAF. 2004. Effect of oral intake of dibutyl phthalate on reproductive parameters of Long Evans rats and pre-pubertal development of their offspring. Toxicology205(1–2):131–137, PMID: 15458798, 10.1016/j.tox.2004.06.045.
Salian S, Doshi T, Vanage G. 2009. Perinatal exposure of rats to bisphenol A affects the fertility of male offspring. Life Sci85(21–22):742–752, PMID: 19837096, 10.1016/j.lfs.2009.10.004.
Santamaría C, Durando M, Muñoz de Toro M, Luque EH, Rodriguez HA, Santamaría C, et al.2016. Ovarian dysfunctions in adult female rat offspring born to mothers perinatally exposed to low doses of bisphenol A. J Steroid Biochem Mol Biol158(2016):220–230, PMID: 26658420, 10.1016/j.jsbmb.2015.11.016.
Schmauss C, Lee-McDermott Z, Medina LR. 2014. Trans-generational effects of early life stress: The role of maternal behavior. Sci Rep4(1):4873, PMID: 24786242, 10.1038/srep04873.
Schneider S, Kaufmann W, Strauss V, van Ravenzwaay B. 2011. Vinclozolin: A feasibility and sensitivity study of the ILSI-HESI F1-extended one-generation rat reproduction protocol. Regul Toxicol Pharmacol59(1):91–100, PMID: 20875480, 10.1016/j.yrtph.2010.09.010.
Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al.2003. The GPR54 gene as a regulator of puberty. N Engl J Med349(17):1614–1627, PMID: 14573733, 10.1056/NEJMoa035322.
Seta D, Della Minder I, Dessì-Fulgheri F, Farabollini F. 2005. Bisphenol-A exposure during pregnancy and lactation affects maternal behavior in rats. Brain Res Bull65(3):255–260, PMID: 15811589, 10.1016/j.brainresbull.2004.11.017.
Shao P, Wang Y, Zhang M, Wen X, Zhang J, Xu Z, et al.2019. The interference of DEHP in precocious puberty of females mediated by the hypothalamic IGF-1/PI3K/Akt/mTOR signaling pathway. Ecotoxicol Environ Saf181:362–369, PMID: 31212184, 10.1016/j.ecoenv.2019.06.017.
Soille P. 1999. Morphological Image Analysis: Principles and Applications. New York, NY: Springer Science & Business Media.
Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH. 2007. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect115(6):876–882, PMID: 17589594, 10.1289/ehp.9882.
Szwarcfarb B, Carbone S, Reynoso R, Bollero G, Ponzo O, Moguilevsky J, et al.2008. Octyl-methoxycinnamate (OMC), an ultraviolet (UV) filter, alters LHRH and amino acid neurotransmitters release from hypothalamus of immature rats. Exp Clin Endocrinol Diabetes116(2):94–98, PMID: 18286425, 10.1055/s-2007-1004589.
Takai R, Hayashi S, Kiyokawa J, Iwata Y, Matsuo S, Suzuki M, et al.2009. Collaborative work on evaluation of ovarian toxicity. 10) two- or four-week repeated dose studies and fertility study of di-(2-ethylhexyl) phthalate (DEHP) in female rats. J Toxicol Sci34 Suppl 1:SP111–9, PMID: 19265277, 10.2131/jts.34.s111.
Taxvig C, Hass U, Axelstad M, Dalgaard M, Boberg J, Andeasen HR, et al.2007. Endocrine-disrupting activities in vivo of the fungicides tebuconazole and epoxiconazole. Toxicol Sci100(2):464–473, PMID: 17785682, 10.1093/toxsci/kfm227.
Terasawa E, Garcia JP, Seminara SB, Keen KL. 2018. Role of kisspeptin and neurokinin B in puberty in female non-human primates. Front Endocrinol (Lausanne)9:148, PMID: 29681889, 10.3389/fendo.2018.00148.
Tkalec Ž, Kosjek T, Snoj Tratnik J, Stajnko A, Runkel AA, Sykiotou M, et al.2021. Exposure of Slovenian children and adolescents to bisphenols, parabens and triclosan: Urinary levels, exposure patterns, determinants of exposure and susceptibility. Environ Int146:106172, PMID: 33113465, 10.1016/j.envint.2020.106172.
Toro CA, Wright H, Aylwin CF, Ojeda SR, Lomniczi A. 2018. Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty. Nat Commun9(1):57, PMID: 29302059, 10.1038/s41467-017-02512-1.
U.S. CDC (U.S. Centers for Disease Control and Prevention).2015. Fourth National Report on Human Exposure to Environmental Chemicals: Updated Tables, February 2015. https://www.cdc.gov/biomonitoring/pdf/FourthReport_UpdatedTables_Feb2015.pdf [accessed 16 May 2020].
Vazquez MJ, Toro CA, Castellano JM, Ruiz-Pino F, Roa J, Beiroa D, et al.2018. SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression. Nat Commun9(1):4194, PMID: 30305620, 10.1038/s41467-018-06459-9.
Veiga-Lopez A, Luense LJ, Christenson LK, Padmanabhan V. 2013. Developmental programming: Gestational bisphenol-A treatment alters trajectory of fetal ovarian gene expression. Endocrinology154(5):1873–1884, PMID: 23525218, 10.1210/en.2012-2129.
Venturelli AC, Meyer KB, Fischer SV, Kita DH, Philipsen RA, Morais RN, et al.2019. Effects of in utero and lactational exposure to phthalates on reproductive development and glycemic homeostasis in rats. Toxicology421:30–40, PMID: 30940548, 10.1016/j.tox.2019.03.008.
Wang X, Chang F, Bai Y, Chen F, Zhang J, Chen L. 2014. Bisphenol A enhances kisspeptin neurons in anteroventral periventricular nucleus of female mice. J Endocrinol221(2):201–213, PMID: 24532816, 10.1530/JOE-13-0475.
Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, et al.2004. Epigenetic programming by maternal behavior. Nat Neurosci7(8):847–854, PMID: 15220929, 10.1038/nn1276.
Wei Y, Han C, Li S, Cui Y, Bao Y, Shi W. 2020. Maternal exposure to bisphenol A during pregnancy interferes ovaries development of F1 female mice. Theriogenology142:138–148, PMID: 31593881, 10.1016/j.theriogenology.2019.09.045.
Wintermantel TM, Campbell RE, Porteous R, Bock D, Grone H-J, Todman MG, et al.2006. Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron52(2):271–280, PMID: 17046690, 10.1016/j.neuron.2006.07.023.
Witchey SK, Fuchs J, Patisaul HB. 2019. Perinatal bisphenol A (BPA) exposure alters brain oxytocin receptor (OTR) expression in a sex- and region- specific manner: A CLARITY-BPA Consortium follow-up study. Neurotoxicology74:139–148, PMID: 31251963, 10.1016/j.neuro.2019.06.007.
Wolstenholme JT, Edwards M, Shetty SRJ, Gatewood JD, Taylor JA, Rissman EF, et al.2012. Gestational exposure to bisphenol A produces transgenerational changes in behaviors and gene expression. Endocrinology153(8):3828–3838, PMID: 22707478, 10.1210/en.2012-1195.
Wolstenholme JT, Goldsby J, Rissman EF. 2013. Transgenerational effects of prenatal bisphenol A on social recognition. Horm Behav64(5):833–839, PMID: 24100195, 10.1016/j.yhbeh.2013.09.007.
Xi W, Lee CKF, Yeung WSB, Giesy JP, Wong MH, Zhang X, et al.2011. Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus-pituitary-gonadal axis of CD-1 mice. Reprod Toxicol31(4):409–417, PMID: 21182934, 10.1016/j.reprotox.2010.12.002.
Xia Y, Ma T, Ji J, Zhang L, Wang Y, Wu J, et al.2020. In utero exposure to DBP stimulates release of GnRH by increasing the secretion of PGE2 in the astrocytes of the hypothalamus in the offspring mice. Ecotoxicol Environ Saf198:110698, PMID: 32388187, 10.1016/j.ecoenv.2020.110698.
Xu C, Chen J-A, Qiu Z, Zhao Q, Luo J, Yang L, et al.2010. Ovotoxicity and PPAR-mediated aromatase downregulation in female Sprague–Dawley rats following combined oral exposure to benzo[a]pyrene and di-(2-ethylhexyl) phthalate. Toxicol Lett199(3):323–332, PMID: 20920559, 10.1016/j.toxlet.2010.09.015.
Yamasaki K, Okuda H, Takeuchi T, Minobe Y. 2009. Effects of in utero through lactational exposure to dicyclohexyl phthalate and p,p′-DDE in Sprague-Dawley rats. Toxicol Lett189(1):14–20, PMID: 19410640, 10.1016/j.toxlet.2009.04.023.
Ye X, Bishop AM, Reidy JA, Needham LL, Calafat AM. 2006. Parabens as urinary biomarkers of exposure in humans. Environ Health Perspect114(12):1843–1846, PMID: 17185273, 10.1289/ehp.9413.
Yeo S-H, Herbison AE. 2014. Estrogen-negative feedback and estrous cyclicity are critically dependent upon estrogen receptor-alpha expression in the arcuate nucleus of adult female mice. Endocrinology155(8):2986–2995, PMID: 24905671, 10.1210/en.2014-1128.
You L, Casanova M, Archibeque-Engle S, Sar M, Fan LQ, Heck HA. 1998. Impaired male sexual development in perinatal Sprague-Dawley and Long-Evans hooded rats exposed in utero and lactationally to p,p′-DDE. Toxicol Sci45(2):162–173, PMID: 9848123, 10.1093/toxsci/45.2.162.
Yu Z, Wang F, Han J, Lu R, Li Q, Cai L, et al.2020. Opposite effects of high- and low-dose di-(2-ethylhexyl) phthalate (DEHP) exposure on puberty onset, oestrous cycle regularity and hypothalamic kisspeptin expression in female rats. Reprod Fertil Dev32(6):610–618, PMID: 32209209, 10.1071/RD19024.
Zalko D, Soto AM, Canlet C, Tremblay-Franco M, Jourdan F, Cabaton NJ. 2016. Bisphenol A exposure disrupts neurotransmitters through modulation of transaminase activity in the brain of rodents. Endocrinology157(5):1736–1739, PMID: 27149041, 10.1210/en.2016-1207.
Zhou C, Gao L, Flaws JA. 2017. Exposure to an environmentally relevant phthalate mixture causes transgenerational effects on female reproduction in mice. Endocrinology158(6):1739–1754, PMID: 28368545, 10.1210/en.2017-00100.
Ziv-Gal A, Wang W, Zhou C, Flaws JA. 2015. The effects of in utero bisphenol a exposure on reproductive capacity in several generations of mice. Toxicol Appl Pharmacol284(3):354–362, PMID: 25771130, 10.1016/j.taap.2015.03.003.
