Richard Christian Jensen1, Dorte Glintborg2, Clara Amalie Gade Timmermann3, Flemming Nielsen3, Henriette Boye Kyhl4, Hanne Frederiksen5, Anna-Maria Andersson5, Anders Juul5, Johannes J Sidelmann6, Helle Raun Andersen3, Philippe Grandjean7, Marianne S Andersen2, Tina Kold Jensen8. 1. Department of Environmental Medicine, University of Southern Denmark, J.B. Winsløws Vej 17A, 5000, Odense C, Denmark; Department of Endocrinology, Odense University Hospital, Søndre Blvd. 29, Odense C, Denmark. Electronic address: rcjensen@health.sdu.dk. 2. Department of Endocrinology, Odense University Hospital, Søndre Blvd. 29, Odense C, Denmark. 3. Department of Environmental Medicine, University of Southern Denmark, J.B. Winsløws Vej 17A, 5000, Odense C, Denmark. 4. Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense University Hospital, Søndre Blvd. 29, 5000, Odense C, Denmark. 5. Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Juliane Maries Vej 6, 2100, Copenhagen OE, Denmark. 6. Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, and Department of Clinical Biochemistry, University Hospital of Southern Denmark, Finsensgade 35, 6700, Esbjerg, Denmark. 7. Department of Environmental Medicine, University of Southern Denmark, J.B. Winsløws Vej 17A, 5000, Odense C, Denmark; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, 677 Huntington Avenue Boston, MA, 02115, USA. 8. Department of Environmental Medicine, University of Southern Denmark, J.B. Winsløws Vej 17A, 5000, Odense C, Denmark; Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense University Hospital, Søndre Blvd. 29, 5000, Odense C, Denmark; Odense Patient Data Explorative Network (OPEN), University of Southern, J. B. Winsløws Vej 9a, Odense C, Denmark.
Abstract
BACKGROUND: Fetal programming of the endocrine system may be affected by exposure to perfluoroalkyl substances (PFAAs), as they easily cross the placental barrier. In vitro studies suggest that PFAAs may disrupt steroidogenesis. "Mini puberty" refers to a transient surge in circulating androgens, androgen precursors, and gonadotropins in infant girls and boys within the first postnatal months. We hypothesize that prenatal PFAA exposure may decrease the concentrations of androgens in mini puberty. OBJECTIVES: To investigate associations between maternal serum PFAA concentrations in early pregnancy and serum concentrations of androgens, their precursors, and gonadotropins during mini puberty in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAAs: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured at median gestational week 12 (IQR: 10, 15) in 1628 women. Among these, offspring serum concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione, 17-hydroxyprogesterone (17-OHP), testosterone, luteinizing (LH) and follicle stimulating hormones (FSH) were measured in 373 children (44% girls; 56% boys) at a mean age of 3.9 (±0.9 SD) months. Multivariate linear regression models were performed to estimate associations. RESULTS: A two-fold increase in maternal PFDA concentration was associated with a reduction in DHEA concentration by -19.6% (95% CI: -32.9%, -3.8%) in girls. In girls, also, the androstenedione and DHEAS concentrations were decreased, albeit non-significantly (p < 0.11), with a two-fold increase in maternal PFDA concentration. In boys, no significant association was found between PFAAs and concentrations of androgens, their precursors, and gonadotropins during mini puberty. CONCLUSION: Prenatal PFDA exposure was associated with significantly lower serum DHEA concentrations and possibly also with lower androstenedione and DHEAS concentrations in female infants at mini puberty. The clinical significance of these findings remains to be elucidated.
BACKGROUND: Fetal programming of the endocrine system may be affected by exposure to perfluoroalkyl substances (PFAAs), as they easily cross the placental barrier. In vitro studies suggest that PFAAs may disrupt steroidogenesis. "Mini puberty" refers to a transient surge in circulating androgens, androgen precursors, and gonadotropins in infantgirls and boys within the first postnatal months. We hypothesize that prenatal PFAA exposure may decrease the concentrations of androgens in mini puberty. OBJECTIVES: To investigate associations between maternal serum PFAA concentrations in early pregnancy and serum concentrations of androgens, their precursors, and gonadotropins during mini puberty in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAAs: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured at median gestational week 12 (IQR: 10, 15) in 1628 women. Among these, offspring serum concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione, 17-hydroxyprogesterone (17-OHP), testosterone, luteinizing (LH) and follicle stimulating hormones (FSH) were measured in 373 children (44% girls; 56% boys) at a mean age of 3.9 (±0.9 SD) months. Multivariate linear regression models were performed to estimate associations. RESULTS: A two-fold increase in maternal PFDA concentration was associated with a reduction in DHEA concentration by -19.6% (95% CI: -32.9%, -3.8%) in girls. In girls, also, the androstenedione and DHEAS concentrations were decreased, albeit non-significantly (p < 0.11), with a two-fold increase in maternal PFDA concentration. In boys, no significant association was found between PFAAs and concentrations of androgens, their precursors, and gonadotropins during mini puberty. CONCLUSION: Prenatal PFDA exposure was associated with significantly lower serum DHEA concentrations and possibly also with lower androstenedione and DHEAS concentrations in female infants at mini puberty. The clinical significance of these findings remains to be elucidated.
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