Skip to content
2000
Volume 22, Issue 2
  • ISSN: 1573-4048
  • E-ISSN: 1875-6581

Abstract

Endocrine-disrupting chemicals (EDCs) are anthropogenic compounds that have garnered significant research consideration due to their harmful effects on human health. These compounds disrupt normal physiological homeostasis by interfering with processes such as hormone synthesis, transport, metabolism, and excretion. Even at low concentrations, EDCs can contribute to severe health issues, including life-threatening cancers and metabolic disorders in humans and animals. Consequently, monitoring EDCs in human populations is a critical area of focus. Preclinical and studies have established the impact of EDCs on hormonal pathways, particularly in male and female gonadal development. Furthermore, biomonitoring studies have detected EDCs in various biological matrices, including those of foetuses, children, and pregnant women. Exposure to EDCs has been associated with complications in the female reproductive system, like premature ovarian failure, precocious puberty, and polycystic ovary syndrome. This review provides a comprehensive summary of the associations between EDC exposure and female reproductive dysfunction, emphasizing potential mechanisms underlying these effects.

Loading

Article metrics loading...

/content/journals/cwhr/10.2174/0115734048361078250515192658
2025-05-23
2026-03-06
Loading full text...

Full text loading...

References

  1. PanJ. LiuP. YuX. ZhangZ. LiuJ. The adverse role of endocrine disrupting chemicals in the reproductive system.Front. Endocrinol.202414132499310.3389/fendo.2023.132499338303976
    [Google Scholar]
  2. LeeD.H. Evidence of the possible harm of endocrine-disrupting chemicals in humans: Ongoing debates and key issues.Endocrinol. Metab.2018331445210.3803/EnM.2018.33.1.4429589387
    [Google Scholar]
  3. WanM.L.Y. CoV.A. El-NezamiH. Endocrine disrupting chemicals and breast cancer: A systematic review of epidemiological studies.Crit. Rev. Food Sci. Nutr.202262246549657610.1080/10408398.2021.190338233819127
    [Google Scholar]
  4. GreenM.P. HarveyA.J. FingerB.J. TarulliG.A. Endocrine disrupting chemicals: Impacts on human fertility and fecundity during the peri-conception period.Environ. Res.202119411069410.1016/j.envres.2020.11069433385395
    [Google Scholar]
  5. MulitaF. AnjumF. Thyroid adenoma.StatPearls.Treasure Island, FLStatPearls Publishing2025
    [Google Scholar]
  6. RattanS. FlawsJ.A. The epigenetic impacts of endocrine disruptors on female reproduction across generations.Biol. Reprod.2019101363564410.1093/biolre/ioz08131077281
    [Google Scholar]
  7. MallozziM. BordiG. GaroC. CasertaD. The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns.Birth Defects Res. C Embryo Today2016108322424210.1002/bdrc.2113727653964
    [Google Scholar]
  8. JayarajR. MeghaP. SreedevP. Review Article. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment.Interdiscip. Toxicol.201693-49010010.1515/intox‑2016‑001228652852
    [Google Scholar]
  9. vonderEmbse, A.N.; Elmore, S.E.; Jackson, K.B.; Habecker, B.A.; Manz, K.E.; Pennell, K.D.; Lein, P.J.; La Merrill, M.A. Developmental exposure to DDT or DDE alters sympathetic innervation of brown adipose in adult female mice.Environ. Health20212013710.1186/s12940‑021‑00721‑233794904
    [Google Scholar]
  10. WangC. YangL. WangS. ZhangZ. YuY. WangM. The classic EDCs, phthalate esters and organochlorines, in relation to abnormal sperm quality: A systematic review with meta-analysis.Sci. Rep.20152016611110.1038/srep1998226804707
    [Google Scholar]
  11. YilmazB. TerekeciH. SandalS. KelestimurF. Endocrine disrupting chemicals: Exposure, effects on human health, mechanism of action, models for testing and strategies for prevention.Rev. Endocr. Metab. Disord.202021112714710.1007/s11154‑019‑09521‑z31792807
    [Google Scholar]
  12. NohynekG.J. BorgertC.J. DietrichD. RozmanK.K. Endocrine disruption: Fact or urban legend?Toxicol. Lett.2013223329530510.1016/j.toxlet.2013.10.02224177261
    [Google Scholar]
  13. ZoellerR.T. BrownT.R. DoanL.L. GoreA.C. SkakkebaekN.E. SotoA.M. WoodruffT.J. Vom SaalF.S. Endocrine-disrupting chemicals and public health protection: A statement of principles from The Endocrine Society.Endocrinology201215394097411010.1210/en.2012‑142222733974
    [Google Scholar]
  14. HuoX. ChenD. HeY. ZhuW. ZhouW. ZhangJ. Bisphenol-a and female infertility: A possible role of gene-environment interactions.Int. J. Environ. Res. Public Health2015129111011111610.3390/ijerph12091110126371021
    [Google Scholar]
  15. NowackN. WittsiepeJ. Kasper-SonnenbergM. WilhelmM. SchölmerichA. Influence of low-level prenatal exposure to PCDD/Fs and PCBs on empathizing, systemizing and autistic traits: Results from the duisburg birth cohort study.PLoS One2015106e012990610.1371/journal.pone.012990626066795
    [Google Scholar]
  16. ChangC.H. TsaiM.S. LinC.L. HouJ.W. WangT.H. TsaiY.A. LiaoK.W. MaoI.F. ChenM.L. The association between nonylphenols and sexual hormones levels among pregnant women: A cohort study in Taiwan.PLoS One201498e10424510.1371/journal.pone.010424525148048
    [Google Scholar]
  17. WangJ. PanL. WuS. LuL. XuY. ZhuY. GuoM. ZhuangS. Recent advances on endocrine disrupting effects of UV filters.Int. J. Environ. Res. Public Health201613878210.3390/ijerph1308078227527194
    [Google Scholar]
  18. WirbiskyS. FreemanJ. Atrazine exposure and reproductive dysfunction through the hypothalamus-pituitary-gonadal (HPG) axis.Toxics20153441445010.3390/toxics304041428713818
    [Google Scholar]
  19. SharmaR.P. SchuhmacherM. KumarV. Review on crosstalk and common mechanisms of endocrine disruptors: Scaffolding to improve PBPK/PD model of EDC mixture.Environ. Int.20179911410.1016/j.envint.2016.09.01627697394
    [Google Scholar]
  20. Montes-GrajalesD. Olivero-VerbelJ. EDCs DataBank: 3D-Structure database of endocrine disrupting chemicals.Toxicology2015327879410.1016/j.tox.2014.11.00625451822
    [Google Scholar]
  21. BoasM. Feldt-RasmussenU. MainK.M. Thyroid effects of endocrine disrupting chemicals.Mol. Cell. Endocrinol.2012355224024810.1016/j.mce.2011.09.00521939731
    [Google Scholar]
  22. SchöpelM. ShkuraO. SeidelJ. KockK. ZhongX. LöffekS. HelfrichI. BachmannH. ScherkenbeckJ. HerrmannC. StollR. Allosteric activation of GDP-bound ras isoforms by bisphenol derivative plasticisers.Int. J. Mol. Sci.2018194113310.3390/ijms1904113329642594
    [Google Scholar]
  23. FenichelP. ChevalierN. Brucker-DavisF. BisphenolA. BisphenolA. An endocrine and metabolic disruptor.Ann. Endocrinol.201374321122010.1016/j.ando.2013.04.00223796010
    [Google Scholar]
  24. EngeliR. RohrerS. VuorinenA. HerdlingerS. KasererT. LeuggerS. SchusterD. OdermattA. Interference of paraben compounds with estrogen metabolism by inhibition of 17β-hydroxysteroid dehydrogenases.Int. J. Mol. Sci.2017189200710.3390/ijms1809200728925944
    [Google Scholar]
  25. HongH. BranhamW.S. NgH.W. MolandC.L. DialS.L. FangH. PerkinsR. SheehanD. TongW. Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.Toxicol. Sci.2015143233334810.1093/toxsci/kfu23125349334
    [Google Scholar]
  26. PtakA. GregoraszczukE.L. Bisphenol A induces leptin receptor expression, creating more binding sites for leptin, and activates the JAK/Stat, MAPK/ERK and PI3K/Akt signalling pathways in human ovarian cancer cell.Toxicol. Lett.2012210333233710.1016/j.toxlet.2012.02.00322343039
    [Google Scholar]
  27. RebuliM.E. CaoJ. SluzasE. DelclosK.B. CamachoL. LewisS.M. VanlandinghamM.M. PatisaulH.B. 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. Sci.2014140119020310.1093/toxsci/kfu07424752507
    [Google Scholar]
  28. CombarnousY. NguyenT.M.D. Comparative overview of the mechanisms of action of hormones and endocrine disruptor compounds.Toxics201971510.3390/toxics701000530682876
    [Google Scholar]
  29. MulitaF. IliopoulosF. TsilivigkosC. TchabashviliL. LiolisE. KaplanisC. PerdikarisI. MaroulisI. Cancer rate of Bethesda category II thyroid nodules.Med. Glas.2021191010.17392/1413‑2134734516
    [Google Scholar]
  30. De CosterS. van LarebekeN. Endocrine-disrupting chemicals: Associated disorders and mechanisms of action.J. Environ. Public Health20122012115210.1155/2012/71369622991565
    [Google Scholar]
  31. ShiJ. LiuC. ChenM. YanJ. WangC. ZuoZ. HeC. The interference effects of bisphenol A on the synthesis of steroid hormones in human ovarian granulosa cells.Environ. Toxicol.202136466567410.1002/tox.2307033258555
    [Google Scholar]
  32. RoundP. DasS. WuT.S. WähäläK. Van PetegemF. HammondG.L. Molecular interactions between sex hormone–binding globulin and nonsteroidal ligands that enhance androgen activity.J. Biol. Chem.202029551202121110.1016/S0021‑9258(17)49880‑231852737
    [Google Scholar]
  33. Linillos-PradilloB. RancanL. ParedesS.D. SchlumpfM. LichtensteigerW. VaraE. TresguerresJ.Á.F. Low dose of BPA induces liver injury through oxidative stress, inflammation and apoptosis in long–evans lactating rats and its perinatal effect on female PND6 offspring.Int. J. Mol. Sci.2023245458510.3390/ijms2405458536902016
    [Google Scholar]
  34. PaliouraE. Diamanti-KandarakisE. Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs).Rev. Endocr. Metab. Disord.201516436537110.1007/s11154‑016‑9326‑726825073
    [Google Scholar]
  35. BouchardM.F. ChevrierJ. HarleyK.G. KogutK. VedarM. CalderonN. TrujilloC. JohnsonC. BradmanA. BarrD.B. EskenaziB. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children.Environ. Health Perspect.201111981189119510.1289/ehp.100318521507776
    [Google Scholar]
  36. ZhaoH. ZhouL. ShangguanA.J. BulunS.E. Aromatase expression and regulation in breast and endometrial cancer.J. Mol. Endocrinol.2016571R19R3310.1530/JME‑15‑031027067638
    [Google Scholar]
  37. KerdivelG. HabauzitD. PakdelF. Assessment and molecular actions of endocrine-disrupting chemicals that interfere with estrogen receptor pathways.Int. J. Endocrinol.201310.1155/2013/501851
    [Google Scholar]
  38. Schüler-ToprakS. SkrzypczakM. GründkerC. OrtmannO. TreeckO. Role of estrogen receptor β, G-protein coupled estrogen receptor and estrogen-related receptors in endometrial and ovarian cancer.Cancers20231510284510.3390/cancers1510284537345182
    [Google Scholar]
  39. ZhangX.L. WangH.S. LiuN. GeL.C. Bisphenol A stimulates the epithelial mesenchymal transition of estrogen negative breast cancer cells via FOXA1 signals.Arch. Biochem. Biophys.2015585101610.1016/j.abb.2015.09.00626363213
    [Google Scholar]
  40. WerderE.J. EngelL.S. SatagopanJ. BlairA. KoutrosS. LerroC.C. AlavanjaM.C. SandlerD.P. Beane FreemanL.E. Herbicide, fumigant, and fungicide use and breast cancer risk among farmers’ wives.Environ. Epidemiol.202043e09710.1097/EE9.000000000000009732613154
    [Google Scholar]
  41. LeeH.R. HwangK.A. NamK.H. KimH.C. ChoiK.C. Progression of breast cancer cells was enhanced by endocrine-disrupting chemicals, triclosan and octylphenol, via an estrogen receptor-dependent signaling pathway in cellular and mouse xenograft models.Chem. Res. Toxicol.201427583484210.1021/tx500015624684733
    [Google Scholar]
  42. BuosoE. MasiM. RacchiM. CorsiniE. Endocrine-disrupting chemicals’ (EDCs) effects on tumour microenvironment and cancer progression: Emerging contribution of RACK1.Int. J. Mol. Sci.20202123922910.3390/ijms2123922933287384
    [Google Scholar]
  43. WangW. CraigZ.R. BasavarajappaM.S. HafnerK.S. FlawsJ.A. Mono-(2-ethylhexyl) phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles.Biol. Reprod.201287615210.1095/biolreprod.112.10246723077170
    [Google Scholar]
  44. SenN. LiuX. CraigZ.R. Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice.Reprod. Toxicol.201553June152210.1016/j.reprotox.2015.02.01225765776
    [Google Scholar]
  45. LeeS.G. KimJ.Y. ChungJ.Y. KimY.J. ParkJ.E. OhS. YoonY.D. YooK.S. YooY.H. KimJ.M. 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 Perspect.2013121666366910.1289/ehp.120582323512349
    [Google Scholar]
  46. CostaE.M.F. SpritzerP.M. HohlA. BachegaT.A.S.S. Effects of endocrine disruptors in the development of the female reproductive tract.Arq. Bras. Endocrinol. Metabol201458215316110.1590/0004‑273000000303124830592
    [Google Scholar]
  47. BodicoatD.H. SchoemakerM.J. JonesM.E. McFaddenE. GriffinJ. AshworthA. SwerdlowA.J. Timing of pubertal stages and breast cancer risk: The breakthrough generations study.Breast Cancer Res.2014161R1810.1186/bcr361324495528
    [Google Scholar]
  48. Eckert-LindC. BuschA.S. PetersenJ.H. BiroF.M. ButlerG. BräunerE.V. JuulA. Worldwide secular trends in age at pubertal onset assessed by breast development among girls.JAMA Pediatr.20201744e19588110.1001/jamapediatrics.2019.588132040143
    [Google Scholar]
  49. Knapczyk-StworaK. NyncaA. SwigonskaS. PauksztoL. JastrzebskiJ.P. WitekP. KoziorowskiM. SlomczynskaM. Effects of neonatal methoxychlor exposure on the ovarian transcriptome in piglets.Anim. Reprod. Sci.202223810695610.1016/j.anireprosci.2022.10695635231789
    [Google Scholar]
  50. MckeeR.H. ButalaJ.H. DavidR.M. GansG. NTP center for the evaluation of risks to human reproduction reports on phthalates: Addressing the data gaps.Reprod. Toxicol.200418112210.1016/j.reprotox.2003.09.002
    [Google Scholar]
  51. LiuJ. YangY. ZhuangS. YangY. LiF. LiuW. Enantioselective endocrine-disrupting effects of bifenthrin on hormone synthesis in rat ovarian cells.Toxicology20112901424910.1016/j.tox.2011.08.01621871944
    [Google Scholar]
  52. StreetM.E. AngeliniS. BernasconiS. BurgioE. CassioA. CatellaniC. CirilloF. DeodatiA. FabbriziE. FanosV. GarganoG. GrossiE. IughettiL. LazzeroniP. MantovaniA. MiglioreL. PalanzaP. PanzicaG. PapiniA.M. ParmigianiS. PredieriB. SartoriC. TridentiG. AmarriS. Current knowledge on endocrine disrupting chemicals (EDCs) from animal biology to humans, from pregnancy to adulthood: Highlights from a national italian meeting.Int. J. Mol. Sci.2018196164710.3390/ijms1906164729865233
    [Google Scholar]
  53. SobolewskiM. BarrettE. Polycystic ovary syndrome: Do endocrine-disrupting chemicals play a role?Semin. Reprod. Med.201432316617610.1055/s‑0034‑137108824715511
    [Google Scholar]
  54. BaptisteC.G. BattistaM.C. TrottierA. BaillargeonJ.P. Insulin and hyperandrogenism in women with polycystic ovary syndrome.J. Steroid Biochem. Mol. Biol.20101221-3425210.1016/j.jsbmb.2009.12.01020036327
    [Google Scholar]
  55. RutkowskaA.Z. Diamanti-KandarakisE. Polycystic ovary syndrome and environmental toxins.Fertil. Steril.2016106494895810.1016/j.fertnstert.2016.08.03127559705
    [Google Scholar]
  56. DongS. TerasakaS. KiyamaR. Bisphenol A induces a rapid activation of Erk1/2 through GPR30 in human breast cancer cells.Environ. Pollut.2011159121221810.1016/j.envpol.2010.09.00420875696
    [Google Scholar]
  57. HoraS. PandeyA.K. JhaS. Biomarker-based targeted therapeutics.Neoplasm201810.5772/intechopen.78377
    [Google Scholar]
  58. CasertaD. Di SegniN. MallozziM. GiovanaleV. MantovaniA. MarciR. MoscariniM. Bisphenol a and the female reproductive tract: An overview of recent laboratory evidence and epidemiological studies.Reprod. Biol. Endocrinol.20141213710.1186/1477‑7827‑12‑3724886252
    [Google Scholar]
  59. SoméE.N. TraoréI.T. TamdambaS. NabaloumB. DraboM.K. Association between pesticide exposure and infertility of couple in the Boucle du Mouhoun region: A case-control study.Clin. Epidemiol. Glob. Health20221710115610.1016/j.cegh.2022.101156
    [Google Scholar]
  60. AbdoliS. MasoumiS.Z. KazemiF. Environmental and occupational factors and higher risk of couple infertility: A systematic review study.Middle East Fertil. Soc. J.20222713310.1186/s43043‑022‑00124‑4
    [Google Scholar]
  61. BajerB. Exercise associated hormonal signals as powerful determinants of an effective fat mass loss.Endocr. Regul.201549315116310.4149/endo_2015_03_15126238498
    [Google Scholar]
  62. WatanabeM. OhnoS. NakajinS. Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines.Toxicol. Lett.20122101959910.1016/j.toxlet.2012.01.02022327052
    [Google Scholar]
  63. KrotzS.P. CarsonS.A. TomeyC. BusterJ.E. Phthalates and bisphenol do not accumulate in human follicular fluid.J. Assist. Reprod. Genet.201229877377710.1007/s10815‑012‑9775‑1
    [Google Scholar]
  64. HassaniS. NamvarM. GhoreishvandiM. AttarchiM. GolabadiM. SeyedmehdiS.M. KhodarahmianM. Menstrual disturbances and hormonal changes in women workers exposed to a mixture of organic solvents in a pharmaceutical company.Med. J. Islam. Repub. Iran201428115625695014
    [Google Scholar]
  65. SamtaniR. SharmaN. GargD. Effects of endocrine-disrupting chemicals and epigenetic modifications in ovarian cancer: A review.Reprod. Sci.201825171810.1177/193371911771126128602118
    [Google Scholar]
  66. LimaS.M. KehmR.D. TerryM.B. Global breast cancer incidence and mortality trends by region, age-groups, and fertility patterns.EClinicalMedicine202138100985
    [Google Scholar]
  67. MallozziM. Endocrine disrupting chemicals and endometrial cancer: An overview of recent laboratory evidence and epidemiological studies.Int. J. Environ. Res. Public Health2017 Mar 22;14333410.3390/ijerph14030334
    [Google Scholar]
  68. StrohsnitterW.C. BertrandK.A. TroisiR. ScottC.G. ChevilleA.L. HooverR.N. PalmerJ.R. VachonC.M. Prenatal diethylstilbestrol exposure and mammographic density.Int. J. Cancer201814361374137810.1002/ijc.3152429658110
    [Google Scholar]
  69. HowardS.G. Developmental exposure to endocrine disrupting chemicals and type 1 diabetes mellitus.Front. Endocrinol.2018951310.3389/fendo.2018.00513
    [Google Scholar]
  70. BodinJ. BøllingA.K. BecherR. KuperF. LøvikM. Nygaard, UC Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice.Toxicol. Sci.2014137231132310.1093/toxsci/kft242
    [Google Scholar]
  71. PetrakisD. VassilopoulouL. MamoulakisC. PsycharakisC. AnifantakiA. SifakisS. DoceaA. TsiaoussisJ. MakrigiannakisA. TsatsakisA. Endocrine disruptors leading to obesity and related diseases.Int. J. Environ. Res. Public Health20171410128210.3390/ijerph1410128229064461
    [Google Scholar]
  72. BatemanM.E. StrongA.L. McLachlanJ.A. BurowM.E. BunnellB.A. The effects of endocrine disruptors on adipogenesis and osteogenesis in mesenchymal stem cells: A review.Front. Endocrinol.20177JAN17110.3389/fendo.2016.0017128119665
    [Google Scholar]
  73. BiemannR. Navarrete SantosA. Navarrete SantosA. RiemannD. KnelangenJ. BlüherM. KochH. FischerB. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows.Biochem. Biophys. Res. Commun.2012417274775210.1016/j.bbrc.2011.12.02822197818
    [Google Scholar]
  74. LiH. FuX. Mechanisms of action of mesenchymal stem cells in cutaneous wound repair and regeneration.Cell Tissue Res.2012348337137710.1007/s00441‑012‑1393‑922447168
    [Google Scholar]
  75. ChiragM. Neonatal rat myocardial extraction HHS public access.Physiol. Behav.20191763139148
    [Google Scholar]
  76. KriegS.A. ShahineL.K. LathiR.B. LathiR.B. Environmental exposure to endocrine-disrupting chemicals and miscarriage.Fertil. Steril.2016106494194710.1016/j.fertnstert.2016.06.04327473347
    [Google Scholar]
  77. MarquardtJ. ChenX. BiE. Septin assembly and remodeling at the cell division site during the cell cycle.Front. Cell Dev. Biol.2021979392010.3389/fcell.2021.79392034901034
    [Google Scholar]
  78. JengH.A. Exposure to endocrine disrupting chemicals and male reproductive health.Front. Public Health201425510.3389/fpubh.2014.0005524926476
    [Google Scholar]
/content/journals/cwhr/10.2174/0115734048361078250515192658
Loading
/content/journals/cwhr/10.2174/0115734048361078250515192658
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test