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Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure

Part of: Liggins Institute, New Zealand and the Japanese DOHaD Society

Published online by Cambridge University Press:  09 January 2018

E. S. Barrett Open the ORCID record for E. S. Barrett [Opens in a new window] ,
K. M. Hoeger ,
S. Sathyanarayana ,
D. H. Abbott ,
J. B. Redmon ,
R. H. N. Nguyen  and
S. H. Swan
E. S. Barrett*
Affiliation:
Department of Epidemiology, Rutgers School of Public Health, Division of Epidemiology and Biostatistics, Environmental and Occupational Health Sciences Institute, Piscataway, NJ, USA Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
K. M. Hoeger
Affiliation:
Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
S. Sathyanarayana
Affiliation:
Departments of Pediatrics, Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA Seattle Children’s Research Institute, Seattle, WA, USA
D. H. Abbott
Affiliation:
Departments of Obstetrics and Gynecology and Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA
J. B. Redmon
Affiliation:
Department of Medicine, University of Minnesota, Minneapolis, MN, USA
R. H. N. Nguyen
Affiliation:
Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
S. H. Swan
Affiliation:
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
*
Address for correspondence: E. S. Barrett, Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA. E-mail Emily.barrett@eohsi.rutgers.edu
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Abstract

Polycystic ovary syndrome (PCOS) affects ~7% of reproductive age women. Although its etiology is unknown, in animals, excess prenatal testosterone (T) exposure induces PCOS-like phenotypes. While measuring fetal T in humans is infeasible, demonstrating in utero androgen exposure using a reliable newborn biomarker, anogenital distance (AGD), would provide evidence for a fetal origin of PCOS and potentially identify girls at risk. Using data from a pregnancy cohort (The Infant Development and Environment Study), we tested the novel hypothesis that infant girls born to women with PCOS have longer AGD, suggesting higher fetal T exposure, than girls born to women without PCOS. During pregnancy, women reported whether they ever had a PCOS diagnosis. After birth, infant girls underwent two AGD measurements: anofourchette distance (AGD-AF) and anoclitoral distance (AGD-AC). We fit adjusted linear regression models to examine the association between maternal PCOS and girls’ AGD. In total, 300 mother–daughter dyads had complete data and 23 mothers reported PCOS. AGD was longer in the daughters of women with a PCOS diagnosis compared with daughters of women with no diagnosis (AGD-AF: β=1.21, P=0.05; AGD-AC: β=1.05, P=0.18). Results were stronger in analyses limited to term births (AGD-AF: β=1.65, P=0.02; AGD-AC: β=1.43, P=0.09). Our study is the first to examine AGD in offspring of women with PCOS. Our results are consistent with findings that women with PCOS have longer AGD and suggest that during PCOS pregnancies, daughters may experience elevated T exposure. Identifying the underlying causes of PCOS may facilitate early identification and intervention for those at risk.

Keywords

AGDfetal programmingPCOSpregnancytestosterone
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 3: Themed Issue: NZ-Japan , June 2018 , pp. 307 - 314
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

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