Background: Exposure to perfluorooctane sulfonate (PFOS) may potentially disturb fetal Leydig cell hormone production and male genital development.

Objectives: We aimed to study the associations between levels of amniotic fluid PFOS, fetal steroid hormone, and insulin-like factor 3 (INSL3) and the prevalence of cryptorchidism and hypospadias.

Methods: Using the Danish National Patient Registry, we selected 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls with stored maternal amniotic fluid samples available in a Danish pregnancy-screening biobank (1980–1996). We used mass spectrometry to measure PFOS in amniotic fluid from 645 persons and steroid hormones in samples from 545 persons. INSL3 was measured by immunoassay from 475 persons. Associations between PFOS concentration in amniotic fluid, hormone levels, and genital malformations were assessed by confounder-adjusted linear and logistic regression.

Results: The highest tertile of PFOS exposure (> 1.4 ng/mL) in amniotic fluid was associated with a 40% (95% CI: –69, –11%) lower INSL3 level and an 18% (95% CI: 7, 29%) higher testosterone level compared with the lowest tertile (< 0.8 ng/mL). Amniotic fluid PFOS concentration was not associated with cryptorchidism or hypospadias.

Conclusions: Environmental PFOS exposure was associated with steroid hormone and INSL3 concentrations in amniotic fluid, but was not associated with cryptorchidism or hypospadias in our study population. Additional studies are needed to determine whether associations with fetal hormone levels may have long-term implications for reproductive health.

Citation: Toft G, Jönsson BA, Bonde JP, Nørgaard-Pedersen B, Hougaard DM, Cohen A, Lindh CH, Ivell R, Anand-Ivell R, Lindhard MS. 2016. Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980–1996). Environ Health Perspect 124:151–156; http://dx.doi.org/10.1289/ehp.1409288

Citation: Toft G, Jönsson BA, Bonde JP, Nørgaard-Pedersen B, Hougaard DM, Cohen A, Lindh CH, Ivell R, Anand-Ivell R, Lindhard MS. 2016. Perfluorooctane sulfonate concentrations in amniotic fluid, biomarkers of fetal Leydig cell function, and cryptorchidism and hypospadias in Danish boys (1980–1996). Environ Health Perspect 124:151–156; http://dx.doi.org/10.1289/ehp.1409288

Address correspondence to G. Toft, Department of Clinical Epidemiology, Aarhus University Hospital, Oluf Palmes Allé 43-45, 8200 Aarhus N, Denmark. Telephone: 45 871 68202. E-mail: [email protected]

We are grateful to Å. Amilon and A. Kristensen for skillful technical assistance.

This study was initiated by generous grants from the Danish Environmental Protection Agency, the Danish Ministry of Interior and Health, Research Centre for Environmental Health’s Fund, the Swedish Council for Working Life and Social Research, Skåne County Council’s Research and Development Foundation, and the Medical Faculty at Lund University, Sweden.

The sponsors had no part in study design, data collection, analysis, or preparation of the manuscript, and they are not responsible for the scientific content and the conclusions expressed.

The authors declare they have no actual or potential competing financial interests.

Received: 2 October 2014 Accepted: 1 June 2015 Advance Publication: 5 June 2015 Final Publication: 1 January 2016

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