The Epigenetic Impacts of Endocrine Disruptors on Female Reproduction Across Generations†

Overview

Journal Biol Reprod

Publisher Oxford University Press

Specialty Reproductive Medicine

Date 2019 May 12

PMID 31077281

Citations 32

Authors

Saniya Rattan

Jodi A Flaws

Affiliations

Soon will be listed here.

Abstract

Humans and animals are repeatedly exposed to endocrine disruptors, many of which are ubiquitous in the environment. Endocrine disruptors interfere with hormone action; thus, causing non-monotonic dose responses that are atypical of standard toxicant exposures. The female reproductive system is particularly susceptible to the effects of endocrine disruptors. Likewise, exposures to endocrine disruptors during developmental periods are particularly concerning because programming during development can be adversely impacted by hormone level changes. Subsequently, developing reproductive tissues can be predisposed to diseases in adulthood and these diseases can be passed down to future generations. The mechanisms of action by which endocrine disruptors cause disease transmission to future generations are thought to include epigenetic modifications. This review highlights the effects of endocrine disruptors on the female reproductive system, with an emphasis on the multi- and transgenerational epigenetic effects of these exposures.

Citing Articles

Prenatal exposure to nitrate alters uterine morphology and gene expression in adult female F1 generation rats.

Cassiani A, Aloia T, Sousa-Vidal E, Podgaec S, Piccinato C, Serrano-Nascimento C Arch Endocrinol Metab. 2025; 68(Spec Issue):e240085.

PMID: 39876961 PMC: 11771761. DOI: 10.20945/2359-4292-2024-0085.

Biochanin a modulates steroidogenesis and cellular metabolism in human granulosa cells through TAS2Rs activation: a spotlight on ovarian function.

Luongo F, Passaponti S, Haxhiu A, Bano I, Ponchia R, Morgante G Reprod Biol Endocrinol. 2025; 23(1):13.

PMID: 39863886 PMC: 11762455. DOI: 10.1186/s12958-025-01344-9.

Endocrine disruptor chemicals exposure and female fertility declining: from pathophysiology to epigenetic risks.

Tricotteaux-Zarqaoui S, Lahimer M, Abou Diwan M, Corona A, Candela P, Cabry R Front Public Health. 2024; 12:1466967.

PMID: 39735741 PMC: 11672798. DOI: 10.3389/fpubh.2024.1466967.

Genetics, Epigenetics, and the Environment: Are Precision Medicine, Provider Compassion, and Social Justice Effective Public Health Measures to Mitigate Disease Risk and Severity?.

Iannaccone P, Ryznar R, Van Winkle L Int J Environ Res Public Health. 2024; 21(11).

PMID: 39595789 PMC: 11593770. DOI: 10.3390/ijerph21111522.

The role of epigenetics in women's reproductive health: the impact of environmental factors.

Yu X, Xu J, Song B, Zhu R, Liu J, Liu Y Front Endocrinol (Lausanne). 2024; 15:1399757.

PMID: 39345884 PMC: 11427273. DOI: 10.3389/fendo.2024.1399757.

References

Giusti R, Iwamoto K, Hatch E . Diethylstilbestrol revisited: a review of the long-term health effects. Ann Intern Med. 1995; 122(10):778-88. DOI: 10.7326/0003-4819-122-10-199505150-00008. View

Craig Z, Wang W, Flaws J . Endocrine-disrupting chemicals in ovarian function: effects on steroidogenesis, metabolism and nuclear receptor signaling. Reproduction. 2011; 142(5):633-46. DOI: 10.1530/REP-11-0136. View

Cauley J . Estrogen and bone health in men and women. Steroids. 2015; 99(Pt A):11-5. DOI: 10.1016/j.steroids.2014.12.010. View

Lovekamp-Swan T, Davis B . Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect. 2003; 111(2):139-45. PMC: 1241340. DOI: 10.1289/ehp.5658. View

Uzumcu M, Zama A, Oruc E . Epigenetic mechanisms in the actions of endocrine-disrupting chemicals: gonadal effects and role in female reproduction. Reprod Domest Anim. 2012; 47 Suppl 4:338-47. PMC: 4151320. DOI: 10.1111/j.1439-0531.2012.02096.x. View

Zhou C, Gao L, Flaws J . Exposure to an Environmentally Relevant Phthalate Mixture Causes Transgenerational Effects on Female Reproduction in Mice. Endocrinology. 2017; 158(6):1739-1754. PMC: 5460945. DOI: 10.1210/en.2017-00100. View

Skinner M . What is an epigenetic transgenerational phenotype? F3 or F2. Reprod Toxicol. 2007; 25(1):2-6. PMC: 2249610. DOI: 10.1016/j.reprotox.2007.09.001. View

Hannon P, Brannick K, Wang W, Flaws J . Mono(2-ethylhexyl) phthalate accelerates early folliculogenesis and inhibits steroidogenesis in cultured mouse whole ovaries and antral follicles. Biol Reprod. 2015; 92(5):120. PMC: 4645979. DOI: 10.1095/biolreprod.115.129148. View

Heindel J, Vandenberg L . Developmental origins of health and disease: a paradigm for understanding disease cause and prevention. Curr Opin Pediatr. 2015; 27(2):248-53. PMC: 4535724. DOI: 10.1097/MOP.0000000000000191. View

10.

Newbold R, Padilla-Banks E, Jefferson W . Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations. Endocrinology. 2006; 147(6 Suppl):S11-7. DOI: 10.1210/en.2005-1164. View

11.

Manikkam M, Haque M, Guerrero-Bosagna C, Nilsson E, Skinner M . Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline. PLoS One. 2014; 9(7):e102091. PMC: 4109920. DOI: 10.1371/journal.pone.0102091. View

12.

Supornsilchai V, Jantarat C, Nosoognoen W, Pornkunwilai S, Wacharasindhu S, Soder O . Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty. J Pediatr Endocrinol Metab. 2016; 29(11):1233-1239. DOI: 10.1515/jpem-2015-0326. View

13.

Kartha R, Subramanian S . Competing endogenous RNAs (ceRNAs): new entrants to the intricacies of gene regulation. Front Genet. 2014; 5:8. PMC: 3906566. DOI: 10.3389/fgene.2014.00008. View

14.

Bruner-Tran K, Gnecco J, Ding T, Glore D, Pensabene V, Osteen K . Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models. Reprod Toxicol. 2016; 68:59-71. PMC: 5237424. DOI: 10.1016/j.reprotox.2016.07.007. View

15.

Nilsson E, Skinner M . Environmentally Induced Epigenetic Transgenerational Inheritance of Reproductive Disease. Biol Reprod. 2015; 93(6):145. PMC: 6058737. DOI: 10.1095/biolreprod.115.134817. View

16.

Merry C, Forrest M, Sabers J, Beard L, Gao X, Hatzoglou M . DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Hum Mol Genet. 2015; 24(21):6240-53. PMC: 4599679. DOI: 10.1093/hmg/ddv343. View

17.

Zhou C, Flaws J . Effects of an Environmentally Relevant Phthalate Mixture on Cultured Mouse Antral Follicles. Toxicol Sci. 2016; 156(1):217-229. PMC: 6075604. DOI: 10.1093/toxsci/kfw245. View

18.

Vasiliu O, Muttineni J, Karmaus W . In utero exposure to organochlorines and age at menarche. Hum Reprod. 2004; 19(7):1506-12. DOI: 10.1093/humrep/deh292. View

19.

Szamatowicz M . How can gynaecologists cope with the silent killer - osteoporosis?. Prz Menopauzalny. 2017; 15(4):189-192. PMC: 5327627. DOI: 10.5114/pm.2016.65682. View

20.

Nilsson E, Klukovich R, Sadler-Riggleman I, Beck D, Xie Y, Yan W . Environmental toxicant induced epigenetic transgenerational inheritance of ovarian pathology and granulosa cell epigenome and transcriptome alterations: ancestral origins of polycystic ovarian syndrome and primary ovarian insufiency. Epigenetics. 2018; 13(8):875-895. PMC: 6224216. DOI: 10.1080/15592294.2018.1521223. View