Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders

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Abstract

Male reproductive development is intricately dependent on fetal androgen action. Consequently, disrupted androgen action during fetal life can interfere with the development of the reproductive system resulting in adverse effects on reproductive function later in life. One biomarker used to evaluate fetal androgen action is the anogenital distance (AGD), the distance between the anus and the external genitalia. A short male AGD is strongly associated with genital malformations at birth and reproductive disorders in adulthood. AGD is therefore used as an effect readout in rodent toxicity studies aimed at testing compounds for endocrine activity and anti-androgenic properties, and in human epidemiological studies to correlate fetal exposure to endocrine disrupting chemicals to feminization of new-born boys. In this review, we have synthesized current data related to intrauterine exposure to xenobiotics and AGD measurements. We discuss the utility of AGD as a retrospective marker of in utero anti-androgenicity and as a predictive marker for male reproductive disorders, both with respect to human health and rodent toxicity studies. Finally, we highlight four areas that need addressing to fully evaluate AGD as a biomarker in both a regulatory and clinical setting.
Original languageEnglish
JournalArchives of Toxicology
Volume93
Issue number2
Pages (from-to)253-272
ISSN0340-5761
DOIs
Publication statusPublished - 2019

Keywords

  • Anogenital distance
  • Endocrine disruptors
  • Reproduction
  • Risks assessment
  • Toxicology

Cite this

@article{b34045ef9c67438d8b9363d985cd0cfb,
title = "Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders",
abstract = "Male reproductive development is intricately dependent on fetal androgen action. Consequently, disrupted androgen action during fetal life can interfere with the development of the reproductive system resulting in adverse effects on reproductive function later in life. One biomarker used to evaluate fetal androgen action is the anogenital distance (AGD), the distance between the anus and the external genitalia. A short male AGD is strongly associated with genital malformations at birth and reproductive disorders in adulthood. AGD is therefore used as an effect readout in rodent toxicity studies aimed at testing compounds for endocrine activity and anti-androgenic properties, and in human epidemiological studies to correlate fetal exposure to endocrine disrupting chemicals to feminization of new-born boys. In this review, we have synthesized current data related to intrauterine exposure to xenobiotics and AGD measurements. We discuss the utility of AGD as a retrospective marker of in utero anti-androgenicity and as a predictive marker for male reproductive disorders, both with respect to human health and rodent toxicity studies. Finally, we highlight four areas that need addressing to fully evaluate AGD as a biomarker in both a regulatory and clinical setting.",
keywords = "Anogenital distance, Endocrine disruptors, Reproduction, Risks assessment, Toxicology",
author = "{Lindgren Schwartz}, {Camilla Victoria} and Sofie Christiansen and Vinggaard, {Anne Marie} and {Axelstad Petersen}, Marta and Ulla Hass and Terje Svingen",
year = "2019",
doi = "10.1007/s00204-018-2350-5",
language = "English",
volume = "93",
pages = "253--272",
journal = "Archives of Toxicology",
issn = "0340-5761",
publisher = "Springer",
number = "2",

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TY - JOUR

T1 - Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders

AU - Lindgren Schwartz, Camilla Victoria

AU - Christiansen, Sofie

AU - Vinggaard, Anne Marie

AU - Axelstad Petersen, Marta

AU - Hass, Ulla

AU - Svingen, Terje

PY - 2019

Y1 - 2019

N2 - Male reproductive development is intricately dependent on fetal androgen action. Consequently, disrupted androgen action during fetal life can interfere with the development of the reproductive system resulting in adverse effects on reproductive function later in life. One biomarker used to evaluate fetal androgen action is the anogenital distance (AGD), the distance between the anus and the external genitalia. A short male AGD is strongly associated with genital malformations at birth and reproductive disorders in adulthood. AGD is therefore used as an effect readout in rodent toxicity studies aimed at testing compounds for endocrine activity and anti-androgenic properties, and in human epidemiological studies to correlate fetal exposure to endocrine disrupting chemicals to feminization of new-born boys. In this review, we have synthesized current data related to intrauterine exposure to xenobiotics and AGD measurements. We discuss the utility of AGD as a retrospective marker of in utero anti-androgenicity and as a predictive marker for male reproductive disorders, both with respect to human health and rodent toxicity studies. Finally, we highlight four areas that need addressing to fully evaluate AGD as a biomarker in both a regulatory and clinical setting.

AB - Male reproductive development is intricately dependent on fetal androgen action. Consequently, disrupted androgen action during fetal life can interfere with the development of the reproductive system resulting in adverse effects on reproductive function later in life. One biomarker used to evaluate fetal androgen action is the anogenital distance (AGD), the distance between the anus and the external genitalia. A short male AGD is strongly associated with genital malformations at birth and reproductive disorders in adulthood. AGD is therefore used as an effect readout in rodent toxicity studies aimed at testing compounds for endocrine activity and anti-androgenic properties, and in human epidemiological studies to correlate fetal exposure to endocrine disrupting chemicals to feminization of new-born boys. In this review, we have synthesized current data related to intrauterine exposure to xenobiotics and AGD measurements. We discuss the utility of AGD as a retrospective marker of in utero anti-androgenicity and as a predictive marker for male reproductive disorders, both with respect to human health and rodent toxicity studies. Finally, we highlight four areas that need addressing to fully evaluate AGD as a biomarker in both a regulatory and clinical setting.

KW - Anogenital distance

KW - Endocrine disruptors

KW - Reproduction

KW - Risks assessment

KW - Toxicology

U2 - 10.1007/s00204-018-2350-5

DO - 10.1007/s00204-018-2350-5

M3 - Review

VL - 93

SP - 253

EP - 272

JO - Archives of Toxicology

JF - Archives of Toxicology

SN - 0340-5761

IS - 2

ER -