Developmental exposure to an environmentally relevant dose of Bisphenol S impairs postnatal growth and disrupts placental transcriptional profile in female rat.
[en] Because of its possible adverse effects on human health and its ubiquitous nature, Bisphenol A (BPA) is gradually being replaced by presumably safer alternatives like Bisphenol S (BPS). However, data regarding the effects of developmental exposure to BPS on pregnancy and fetal outcomes are very scarce. Here we show that perinatal exposure to BPS at a very low dose significantly impairs postnatal growth and affects the placental transcriptome in rats. Oral exposure one week before mating and during gestation and lactation to a very low dose of BPS (25 ng/kg/day) is associated with impaired postnatal growth without significant difference in fetal weight on gestational day 18 in females. In contrast, in males, exposure to BPS 25 decreased fetal weight on gestational day 18 but growth restriction did not persist into adulthood. In female, exposure to this very low dose of BPS decreased the placental mRNA expression of fucosyltransferase2 (Fut2), pregnancy-specific glycoprotein 22 (Psg22), Wnt family member 7b (Wnt7b) which are involved in early placental development. Placental DNA methylation of steroid receptor coactivator 2 (src2), a key mediator of steroid induced decidualization, was significantly reduced, while placental src2 mRNA expression was unaffected. These results suggest that early exposure to a very low dose of BPS has long term consequences on growth trajectory and is associated with placental dysregulation.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
FUDVOYE, Julie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie
Lopez-Rodriguez, D; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium
Franssen, D; GIGA Neurosciences, Neuroendocrinology Unit, University of Liège, Liège, Belgium
Terwagne, Quentin ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie
Lavergne, Arnaud ; Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA)
Donneau, Anne-Françoise ; Université de Liège - ULiège > Département des sciences de la santé publique
Munaut, Carine ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Dehan, P; Experimental Pathology, University of Liège, Liège, Liège, Belgium
Lomniczi, A; Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Parent, Anne-Simone ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Language :
English
Title :
Developmental exposure to an environmentally relevant dose of Bisphenol S impairs postnatal growth and disrupts placental transcriptional profile in female rat.
F.R.S.-FNRS - Fund for Scientific Research Leon Fredericq Foundation
Funding text :
This research was supported by the FRS-FNRS (Belgian National Foundation for Research, CDR-J013019F-33661942), the University of Li\u00E8ge and the University Hospital of Li\u00E8ge.
Adu-Gyamfi, E.A., Rosenfeld, C., Tuteja, G., The impact of Bisphenol A on the placenta. Biol. Reprod. 17:106(5) (2022), 826–834, 10.1093/biolre/ioac001.
Algonaiman, R., Almutairi, A., Al-Zhrani, M., Barakat, H., Effects of prenatal exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, on OFfspring's Health: Evidence from Epidemiological and Experimental Studies. Biomolecules, 13(11), 2023, 1616, 10.3390/biom13111616.
Andrews, S., Krueger, C., Mellado-Lopez, M., Hemberger, M., Dean, W., et al. Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B. Nat. Commun., 14(1), 2023, 371, 10.1038/s41467-023-36019-9.
Balicco A., Bidondo, M.L., Fillol, C., Gane, J., Oleko, A., Saoudi, A. et al. 2019. Imprégnation de la population française par les bisphénols A, S et F. Programme national de biosurveillance, Esteban 2014-2016. Santé publique France.
Beausoleil, C., Le Magueresse-Battistoni, B., Viguié, C., Babajko, S., Canivenc-Lavier, M.C., Chevalier, N., Emond, C., Habert, R., Picard-Hagen, N., Mhaouty-Kodja, S., Regulatory and academic studies to derive reference values for human health: The case of bisphenol S. Environ Res., 204(Pt C), 2022, 112233, 10.1016/j.envres.2021.112233.
Betancourt, A.M., Eltoum, I.A., Desmond, R.A., Russo, J., Lamartiniere, C.A., In utero exposure to Bisphenol A shifts the window of susceptibility for mammary carcinogenesis in the rat. Environ. Health Perspect. 118:11 (2010), 1614–1619, 10.1289/ehp.1002148.
Bianco-Miotto, T., Craig, J.M., Gasser, Y.P., van Dijk, S.J., Ozanne, S.E., Epigenetics and DOHaD: from basics to birth and beyond. J. Dev. Orig. Health Dis. 8:5 (2017), 513–519, 10.1017/S2040174417000733.
Blois, S.M., Tirado-González, I., Wu, J., Barrientos, G., Johnson, B., Warren, J., Freitag, N., Early expression of pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice. Biol. Reprod., 86(6), 2012, 191, 10.1095/biolreprod.111.098251.
Brulport, A., Vaiman, D., Chagnon, M.-C., Le Corre, L., Obesogen effect of bisphenol s alters MRNA expression and DNA methylation profiling in male mouse liver. Chemosphere, 241, 2020, 125092, 10.1016/j.chemosphere.2019.125092.
Calafat, A.M., Kuklenyik, Z., Reidy, J.A., Caudill, S.P., Ekong, J., Needham, L.L., Urinary concentrations of Bisphenol A and 4-nonylphenol in a human reference population. Environ. Health Perspect. 113:4 (2005), 391–395, 10.1289/ehp.7534.
Calafat, A.M., Ye, X., Wong, L.Y., Reidy, J.A., Needham, L.L., Exposure of the U.S. Population to Bisphenol A and 4-Tertiary-Octylphenol: 2003-2004. Environ. Health Perspect. 116:1 (2008), 39–44, 10.1289/ehp.10753.
Chen, D., Kannan, K., Tan, H., Zheng, Z., Feng, Y.L., Wu, Y., Widelka, M., Bisphenol analogues other than BPA: environmental occurrence, human exposure, and toxicity-A review. Environ. Sc. Technol. 50:11 (2016), 5438–5453, 10.1021/acs.est.5b05387.
Chen, E., Santana da Cruz, R., Nascimento, A., Joshi, M., Pereira, D., Paternal DDT exposure induces sex-specific programming of fetal growth, placenta development and offspring's health phenotypes in a mouse model. Sci. Rep., 30(14(1)), 2024, 7567, 10.1038/s41598-024-58176-7.
Covaci, A., Den Hond, E., Geens, T., Govarts, E., Koppen, G., Frederiksen, H., Knudsen, L., et al. Urinary BPA measurements in children and mothers from six European member states: overall results and determinants of exposure. Environ. Res. 141 (2015), 77–85, 10.1016/j.envres.2014.08.008.
Dasgupta, S., Lonard, D.M., O'Malley, B.W., Nuclear receptor coactivators: master regulators of human health and disease. Annu. Rev. Med. 65 (2014), 279–292, 10.1146/annurev-med-051812-145316.
Demeneix, B., Slama, R., Endocrine disruptors: from scientific evidence to human health protection. Policy Department for Citizens’ Rights and Constitutional Affairs, Directorate General for Internal Policies of the Union, 2019, European Parliament, Brussels, Belgium 132p Petitions. PE 608.866.
Domino, S.E., Hurd, A.E., LacZ expression in Fut2-LacZ reporter mice reveals estrogen-regulated endocervical glandular expression during estrous cycle, hormone replacement, and pregnancy. Glycobiology 14:2 (2004), 169–175, 10.1093/glycob/cwh019.
Domino, S.E., Zhang, L., Gillespie, P.J., Saunders, T.L., Lowe, J.B., Deficiency of reproductive tract Alpha(1,2)Fucosylated glycans and normal fertility in mice with targeted deletions of the FUT1 or FUT2 Alpha(1,2)Fucosyltransferase Locus. Mol. Cel. Biol. 21:24 (2001), 8336–8345, 10.1128/MCB.21.24.8336-8345.2001.
Edlow, A.G., Chen, M., Smith, N.A., Lu, C., McElrath, T.F., Fetal Bisphenol A exposure: concentration of conjugated and unconjugated bisphenol a in amniotic fluid in the second and third trimesters. Reprod. Toxicol. 34:1 (2012), 1–7, 10.1016/j.reprotox.2012.03.009.
Engel, S.M., Levy, B., Liu, Z., Kaplan, D., Wolff, M.S., Xenobiotic phenols in early pregnancy amniotic fluid. Reprod. Toxicol. 21:1 (2006), 110–112, 10.1016/j.reprotox.2005.07.007.
Escriva, L., Hanberg, A., Zilliacus, J., Beronius, A., Assessment of the endocrine disrupting properties of Bisphenol AF according to the EU criteria and ECHA/EFSA guidance. EFSA J., 17(S2), 2019, 170914, 10.2903/j.efsa.2019.e170914.
Ferguson, K.K., Meeker, J.D., Cantonwine, D.E., Mukherjee, B., Pace, G.G., Weller, D., McElrath, T.F., Environmental phenol associations with ultrasound and delivery measures of fetal growth. Environ. Intern. 112 (2018), 243–250, 10.1016/j.envint.2017.12.011.
Franssen, D., Ioannou, Y.S., Alvarez-real, A., Gerard, A., Mueller, J.K., Heger, S., Bourguignon, J.-P., Parent, A.-S., Pubertal timing after neonatal diethylstilbestrol exposure in female rats: neuroendocrine vs peripheral effects and additive role of prenatal food restriction. Reprod. Toxicol. 44 (2014), 63–72, 10.1016/j.reprotox.2013.10.006.
Geens, T., Aerts, D., Berthot, C., Bourguignon, J.-P., Goeyens, L., Lecomte, P., Maghuin-Rogister, G., et al. A review of dietary and non-dietary exposure to Bisphenol-A. Food Chem. Toxicol.: Int. J. Publ. Br. Ind. Biol. Res. Assoc. 50:10 (2012), 3725–3740, 10.1016/j.fct.2012.07.059.
Gingrich, J., Pu, Y., Roberts, J., Karthikraj, R., Kannan, K., Ehrhardt, R., Veiga-Lopez, A., Gestational Bisphenol S impairs placental endocrine function and the fusogenic trophoblast signaling pathway. Arch. Toxicol. 92:5 (2018), 1861–1876, 10.1007/s00204-018-2191-2.
Gingrich, J., Ticiani, E., Veiga-Lopez, A., Placenta disrupted: endocrine disrupting chemicals and pregnancy. Trends Endocrinol. Metab. 31:7 (2020), 508–524, 10.1016/j.tem.2020.03.003.
Goodrich, J.M., Ingle, M.E., Domino, S.E., Treadwell, M.C., Dolinoy, D.C., Burant, C., Meeker, J.D., Padmanabhan, V., First trimester maternal exposures to endocrine disrupting chemicals and metals and fetal size in the Michigan mother-infant pairs study. J. Dev. Orig. Health Dis. 10:4 (2019), 447–458, 10.1017/S204017441800106X.
Gore, A.C., Chappell, V.A., Fenton, S.E., Flaws, J.A., Nadal, A., Prins, G.S., Toppari, J., Zoeller, R.T., « EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals ». Endocr. Rev. 36:6 (2015), E1–150, 10.1210/er.2015-1010.
Hu, J., Zhao, H., Braun, J.M., Zheng, T., Zhang, B., Xia, W., Zhang, W., et al. Associations of Trimester-Specific Exposure to Bisphenols with Size at Birth: A Chinese Prenatal Cohort Study. Environ. Health Perspect., 127(10), 2019, 107001, 10.1289/EHP4664.
Ikezuki, Y., Tsutsumi, O., Takai, Y., Kamei, Y., Taketani, Y., Determination of Bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum. Reprod. 17:11 (2002), 2839–2841, 10.1093/humrep/17.11.2839.
Jeong, J.-W., Lee, K.Y., Han, S.J., Aronow, B.J., Lydon, J.P., O'Malley, B.W., DeMayo, F.J., The P160 Steroid Receptor Coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression. Endocrinology 148:9 (2007), 4238–4250, 10.1210/en.2007-0122.
Kaimal, A., Al Mansi, M.H., Bou Dagher, J., Pope, C., Varghese, M.G., Rudi, T., Almond, A., et al. Prenatal exposure to bisphenols affects pregnancy outcomes and offspring development in rats. Chemosphere, 276, 2021, 130118, 10.1016/j.chemosphere.2021.130118.
Kim, S., Park, E., Park, E.K., Lee, S., Kwon, J.A., Shin, B.H., Kang, S., Park, E.Y., Kim, B., Urinary concentrations of bisphenol mixtures during pregnancy and birth outcomes: the MAKE study. Int J. Environ. Res Public Health, 18(19), 2021, 10098, 10.3390/ijerph181910098.
Knöfler, M., Haider, S., Saleh, L., Pollheimer, J., Gamage, T., James, J., Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell. Mol. Life Sci. 76:18 (2019), 3479–3496, 10.1007/s00018-019-03104-6.
Kolatorova, L., Vitku, J., Hampl, R., Adamcova, K., Skodova, T., Simkova, M., Parizek, A., Starka, L., Duskova, M., Exposure to Bisphenols and parabens during pregnancy and relations to steroid changes. Environ. Res. 163 (2018), 115–122, 10.1016/j.envres.2018.01.031.
Kommagani, R., Szwarc, R.M., Kovanci, E., Gibbons, W.E., Putluri, N., Maity, S., Creighton, C.J., et al. Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. PLoS Genet., 9(10), 2013, e1003900, 10.1371/journal.pgen.1003900.
Krueger, F., Andrews, S., Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27:11 (2011), 1571–1572, 10.1093/bioinformatics/btr167.
Li, H., Huang, Q., Liu, H., Garmire, L.X., Single cell transcriptome research in human placenta. Reprod 160:6 (2020), R155–R167, 10.1530/REP-20-0231.
Liang, F., Huo, X., Wang, W., Li, Y., Zhang, J., Feng, Y., Wang, Y., Association of Bisphenol A or Bisphenol S exposure with oxidative stress and immune disturbance among unexplained recurrent spontaneous abortion women. Chemosphere, 257, 2020, 127035, 10.1016/j.chemosphere.2020.127035.
Liao, C., Liu, F., Guo, Y., Moon, Y.-B., Nakata, H., Wu, Q., Kannan, K., Occurrence of eight Bisphenol analogues in indoor dust from the United States and Several Asian countries: implications for human exposure. Environ. Sci. Technol. 46:16 (2012), 9138–9145, 10.1021/es302004w.
Love, M., Huber, W., Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15(12), 2014, 550, 10.1186/s13059-014-0550-8.
Mao, J., Jain, A., Denslow, N.D., Nouri, M.-Z., Chen, S., Wang, T., Zhu, N., et al. Bisphenol A and Bisphenol S disruptions of the mouse placenta and potential effects on the placenta-brain axis. Proc. Natl. Acad. Sci. USA 117:9 (2020), 4642–4652, 10.1073/pnas.1919563117.
Miller, J.L., Grant, P.A., The role of DNA methylation and histone modifications in transcriptional regulation in humans. Sub-Cell. Biochem. 61 (2013), 289–317, 10.1007/978-94-007-4525-4_13.
Mukherjee, A., Amato, P., Allred, D.C., Fernandez-Valdivia, R., Nguyen, J., O'Malley, B.W., DeMayo, F.J., Lydon, J.P., Steroid receptor coactivator 2 is essential for progesterone-dependent uterine function and mammary morphogenesis: insights from the mouse-implications for the human. J. Steroid Biochem. Mol. Biol. 102:1‑5 (2006), 22–31, 10.1016/j.jsbmb.2006.09.007.
Mukherjee, A., Soyal, S.M., Fernandez-Valdivia, R., Gehin, M., Chambon, P., Demayo, F.J., Lydon, J.P., O'Malley, B.W., Steroid receptor coactivator 2 is critical for progesterone-dependent uterine function and mammary morphogenesis in the mouse. Mol. Cel. Biol. 26:17 (2006), 6571–6583, 10.1128/MCB.00654-06.
Mustieles, V., Williams, P.L., Fernandez, M.F., Mínguez-Alarcón, L., Ford, J.B., Calafat, A.M., Hauser, R., Messerlian, C. et Environment, Reproductive Health (EARTH) Study Team, Maternal and paternal preconception exposure to bisphenols and size at birth. Hum. Reprod. 33:8 (2018), 1528–1537, 10.1093/humrep/dey234.
Parr, B.A., Cornish, V.A., Cybulsky, M.I., McMahon, A.P., Wnt7b regulates placental development in mice. Dev. Biol. 237:2 (2001), 324–332, 10.1006/dbio.2001.0373.
Pfaffl, M.W., A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res., 29(9), 2001, e45 PMID: 11328886, 10.1093/nar/29.9.e45.
Qu, L., Yin, Y., Yin, T., Zhang, X., Zhou, X., Sun, L., NCOA2-induced secretion of leptin leads to fetal growth restriction via the NF-κB signaling pathway. Ann. Transl. Med. Feb, 28(11(4)), 2023, 166 doi: 10.21037.
Rochester, J.R., Bisphenol A and human health: a review of the literature. Reprod. Toxicol. 42 (2013), 132–155, 10.1016/j.reprotox.2013.08.008.
Salian-Mehta, S., Doshi, T., Vanage, G., Exposure of neonatal rats to the endocrine disrupter Bisphenol A affects ontogenic expression pattern of testicular steroid receptors and their coregulators. J. Ap. Toxicol. 34:3 (2014), 307–318, 10.1002/jat.2882.
Schönfelder, G., Wittfoht, W., Hopp, H., Talsness, C.E., Paul, M., Chahoud, I., Parent Bisphenol A accumulation in the human maternal-fetal-placental unit. Environ. Health Perspect. 110:11 (2002), A703–A707, 10.1289/ehp.110-1241091.
Strakovsky, R.S., Schantz, S.L., Impacts of Bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta. Environ. Epigenet., 4(3), 2018, dvy022, 10.1093/eep/dvy022.
Szwarc, M.M., Kommagani, R., Lessey, B., Lydon, J., The p160/steroid receptor coactivator family: potent arbiters of uterine physiology and dysfunction. Biol. Reprod., 91(5), 2014, 122 doi: 10.1095.
Tait, S., Tassinari, R., Maranghi, F., Mantovani, A., Bisphenol A affects placental layers morphology and angiogenesis during early pregnancy phase in mice. J. Appl. Toxicol. 35:11 (2015), 1278–1291, 10.1002/jat.3176.
Taniguchi, K., Kawai, T., Hata, K., Placental development and nutritional environment. Adv. Exp. Med. Biol. 1012 (2018), 63–73, 10.1007/978-981-10-5526-3_7.
Tian, F.-Y., Everson, T.M., Lester, B., Punshon, T., Jackson, B.P., Hao, K., Lesseur, C., Chen, J., Karagas, M.R., Marsit, C.J., Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: an epigenome-wide study of two U.S. birth cohorts. Environ. Intern., 137, 2020, 105508, 10.1016/j.envint.2020.105508.
Toro, C.A., Wright, H., Aylwin, C.F., Ojeda, S.R., Lomniczi, A., Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty. Nat. Commun., 9(1), 2018, 57, 10.1038/s41467-017-02512-1.
Vandenberg, L.N., Chahoud, I., Heindel, J.J., Padmanabhan, V., Paumgartten, F., Schoenfelder, G., Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to Bisphenol A. Environ. Health Perspect. 118:8 (2010), 1055–1070, 10.1289/ehp.0901716.
Vasconcelos, S., Caniçais, C., Chuva de Sousa Lopes, S., Marques, C.J., Doria, S., The role of DNA hydroxymethylation and TET enzymes in placental development and pregnancy outcome. Clin. Epigenet., 15(1), 2023, 66, 10.1186/s13148-023-01483.
Vrooman, L.A., Xin, F., Bartolomei, M.S., Morphologic and molecular changes in the placenta: what we can learn from environmental exposures. Fertil. Steril. 106:4 (2016), 930–940, 10.1016/j.fertnstert.2016.08.016.
Wan, Y., Huo, W., Xu, S., Zheng, T., Zhang, B., Li, Y., Zhou, A., et al. Relationship between maternal exposure to Bisphenol S and pregnancy duration. Environ. Pollut. 238 (2018), 717–724, 10.1016/j.envpol.2018.03.057.
World Health Organization, International Programme on Chemical Safety (WHO-IPCS), 2002. In: Damstra, T., Barlow, S., Bergman, A., Kavlock, R., Van Der Kraak,G. (Eds.),Global Assessment of the State-of-the-Science of EndocrineDisrupters. World Health Organization, Geneva.
Wu, L.-H., Zhang, X.M., Wang, F., Gao, C.J., Chen, D., Palumbo, J.-R., Guo, Y., Zeng, E.Y., Occurrence of Bisphenol S in the environment and implications for human exposure: a short review. Sc. Total Environ. 615 (2018), 87–98, 10.1016/j.scitotenv.2017.09.194.
Yamada, H., Furuta, I., Kato, E.H., Kataoka, S., Usuki, Y., Kobashi, G., Sata, F., Kishi, R., Fujimoto, S., Maternal serum and amniotic fluid Bisphenol A concentrations in the early second trimester. Reprod. Toxicol. 16:6 (2002), 735–739, 10.1016/s0890-6238(02)00051-5.
Zhang, B., He, Y., Zhu, H., Huang, X., Bai, X., Kannan, K., Zhang, T., Concentrations of Bisphenol A and its alternatives in paired maternal-fetal urine, serum and amniotic fluid from an e-waste dismantling area in China. Environ. Intern., 136, 2020, 105407, 10.1016/j.envint.2019.105407.
Zhou, B., Yang, P., Deng, Y.-L., Zeng, Q., Lu, W.-Q., Mei, S.-R., Prenatal exposure to Bisphenol a and its analogues (Bisphenol F and S) and ultrasound parameters of fetal growth. Chemosphere, 246, 2020, 125805, 10.1016/j.chemosphere.2019.125805.
Zhu, D., Gong, X., Miao, L., Fang, J., Zhang, J., EfficienT Induction of Syncytiotrophoblast Layer II cells from trophoblast stem cells by canonical Wnt Signaling activation. Stem Cell Rep. 9:6 (2017), 2034–2049, 10.1016/j.stemcr.2017.10.014.
