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Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review

Author

Listed:
  • Saira Amir

    (Department of Biosciences, COMSATS University Islamabad, Islamabad 44000, Pakistan)

  • Syed Tahir Abbas Shah

    (Department of Biosciences, COMSATS University Islamabad, Islamabad 44000, Pakistan)

  • Charalampos Mamoulakis

    (Department of Urology, University General Hospital of Heraklion, Medical School, University of Crete, 700 13 Heraklion, Greece)

  • Anca Oana Docea

    (Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy, Petru Rares, 200349 Craiova, Romania)

  • Olga-Ioanna Kalantzi

    (Department of Environment, University of Aegean, University Hill, 81100 Mytilini, Greece)

  • Athanasios Zachariou

    (Department of Urology, Ioannina University School of Medicine, 45110 Ioannina, Greece)

  • Daniela Calina

    (Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania)

  • Felix Carvalho

    (UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal)

  • Nikolaos Sofikitis

    (Department of Urology, Ioannina University School of Medicine, 45110 Ioannina, Greece)

  • Antonios Makrigiannakis

    (Department of Obstetrics and Gynecology, Medical School, University of Crete, 71003 Heraklion, Greece)

  • Aristidis Tsatsakis

    (Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece)

Abstract

Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.

Suggested Citation

  • Saira Amir & Syed Tahir Abbas Shah & Charalampos Mamoulakis & Anca Oana Docea & Olga-Ioanna Kalantzi & Athanasios Zachariou & Daniela Calina & Felix Carvalho & Nikolaos Sofikitis & Antonios Makrigiann, 2021. "Endocrine Disruptors Acting on Estrogen and Androgen Pathways Cause Reproductive Disorders through Multiple Mechanisms: A Review," IJERPH, MDPI, vol. 18(4), pages 1-20, February.
    • Handle: RePEc:gam:jijerp:v:18:y:2021:i:4:p:1464-:d:493169
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    References listed on IDEAS

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    Cited by:

    1. Roberta Tassinari & Francesca Maranghi, 2021. "Rodent Model of Gender-Affirming Hormone Therapies as Specific Tool for Identifying Susceptibility and Vulnerability of Transgender People and Future Applications for Risk Assessment," IJERPH, MDPI, vol. 18(23), pages 1-14, November.

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