Prenatal antifungal exposure disrupts fetal steroidogenesis and is associated with persistent effects in children
Abstract
Background: Exposure to endocrine-disrupting chemicals (EDCs) during fetal life is associated with reproductive disorders in humans. While research has largely focused on environmental EDCs and developmental exposure, some pharmaceuticals, including commonly used antifungal agents, also possess endocrine-disrupting properties. We investigate whether prenatal exposure to over-the-counter antifungal drugs is associated with altered fetal and postnatal steroidogenesis and reproductive development. Methods: We combined epidemiological, experimental, and translational approaches using data from a prospective mother-child cohort (n = 589), ex vivo human fetal adrenal cultures, and in vivo rat models. Maternal antifungal use during pregnancy was assessed prospectively, and associations with fetal growth, anogenital distance (AGD), penile measurements, and circulating steroid hormone levels during infancy were evaluated. Experimental studies examined the effects of selected antifungal agents on steroidogenesis in cultured human fetal adrenals and gestationally exposed Sprague-Dawley rats. Results: Early-pregnancy antifungal exposure is associated with reduced circulating steroid hormone levels and indicators of diminished androgen action, including decreased penile width at infancy. In contrast, exposure during mid-to-late pregnancy is associated with elevated steroid hormone levels and longer AGD in both female fetuses and male infants. Consistent with these observations, the antifungal agent clotrimazole reduces progesterone levels in human fetal adrenal cultures and in gestationally exposed rats, whereas miconazole increases AGD in rats. Conclusions: These translational findings suggest that commonly used antifungal agents alter fetal adrenal steroidogenesis and influence reproductive development, with effects persisting into postnatal life. Given their widespread use and over-the-counter availability, the safety of topical azole use during pregnancy may warrant re-evaluation.
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BibTeX
@article{mola2026prenatal,
title = {{Prenatal antifungal exposure disrupts fetal steroidogenesis and is associated with persistent effects in children}},
author = {Gylli Mola and Monica Kam Draskau and Anne Jørgensen and Frédéric Chalmel and Cecilie Melau and Bertrand Evrard and Karen Mandrup and Hanne Hegaard and Trine Koch Hueg and Hanne Frederiksen and Christa E Flück and Anna-Maria Andersson and Anders Juul and Kristian Almstrup and Margit Bistrup Fischer and Terje Svingen and Casper P Hagen},
journal = {Communications Medicine},
year = {2026},
month = sep,
doi = {10.1038/s43856-026-01815-z},
url = {https://hal.science/hal-05747224v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Prenatal antifungal exposure disrupts fetal steroidogenesis and is associated with persistent effects in children
AU - Gylli Mola
AU - Monica Kam Draskau
AU - Anne Jørgensen
AU - Frédéric Chalmel
AU - Cecilie Melau
AU - Bertrand Evrard
AU - Karen Mandrup
AU - Hanne Hegaard
AU - Trine Koch Hueg
AU - Hanne Frederiksen
AU - Christa E Flück
AU - Anna-Maria Andersson
AU - Anders Juul
AU - Kristian Almstrup
AU - Margit Bistrup Fischer
AU - Terje Svingen
AU - Casper P Hagen
PY - 2026
DA - 2026/09/11
JO - Communications Medicine
DO - 10.1038/s43856-026-01815-z
UR - https://hal.science/hal-05747224v1
AB - Background: Exposure to endocrine-disrupting chemicals (EDCs) during fetal life is associated with reproductive disorders in humans. While research has largely focused on environmental EDCs and developmental exposure, some pharmaceuticals, including commonly used antifungal agents, also possess endocrine-disrupting properties. We investigate whether prenatal exposure to over-the-counter antifungal drugs is associated with altered fetal and postnatal steroidogenesis and reproductive development. Methods: We combined epidemiological, experimental, and translational approaches using data from a prospective mother-child cohort (n = 589), ex vivo human fetal adrenal cultures, and in vivo rat models. Maternal antifungal use during pregnancy was assessed prospectively, and associations with fetal growth, anogenital distance (AGD), penile measurements, and circulating steroid hormone levels during infancy were evaluated. Experimental studies examined the effects of selected antifungal agents on steroidogenesis in cultured human fetal adrenals and gestationally exposed Sprague-Dawley rats. Results: Early-pregnancy antifungal exposure is associated with reduced circulating steroid hormone levels and indicators of diminished androgen action, including decreased penile width at infancy. In contrast, exposure during mid-to-late pregnancy is associated with elevated steroid hormone levels and longer AGD in both female fetuses and male infants. Consistent with these observations, the antifungal agent clotrimazole reduces progesterone levels in human fetal adrenal cultures and in gestationally exposed rats, whereas miconazole increases AGD in rats. Conclusions: These translational findings suggest that commonly used antifungal agents alter fetal adrenal steroidogenesis and influence reproductive development, with effects persisting into postnatal life. Given their widespread use and over-the-counter availability, the safety of topical azole use during pregnancy may warrant re-evaluation.
SN - 2730-664X
ER -