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Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.
National and Kapodistrian University of Athens (NKUA), Greece..
National and Kapodistrian University of Athens (NKUA), Greece; School of Health Sciences, NKUA, Greece..
National and Kapodistrian University of Athens (NKUA), Greece..
Karolinska Institutet, Sweden..
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, p. 1-17, article id 6424Article in journal (Refereed) Published
Abstract [en]

The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1st trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenita I distance (AGD) in their baby boys. Mice were treated with 0, 0.26, 2.6 and 13 mg/kg/d of the mixture, corresponding to 0x, 10x, 100x, 500x levels detected in the pregnant women. Adverse outcomes detected in the reproductive system of the offspring in pre-puberty and adulthood included reduced AGD index and gonadal weight, changes in gonadal histology and altered expression of key regulators of gonadal growth and steroidogenesis. Most aberrations were apparent in both sexes, though more pronounced in males, and exhibited a non-monotonic pattern. The phthalate mixture directly affected expression of steroidogenesis as demonstrated in a relevant in vitro model. The detected adversities at exposures close to the levels detected in pregnant women, raise concern on the existing safety limits for early-life human exposures and emphasizes the need for re-evaluation of the exposure risk.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 9, no 1, p. 1-17, article id 6424
Keywords [en]
Testis endocrine disruption, germ-cell number, anogenital distance, in-utero, dose-response, fetal testis, diethylhexyl phthalate, sexual-differentiation, perinatal exposure, prenatal exposure
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
URN: urn:nbn:se:kau:diva-71996DOI: 10.1038/s41598-019-42377-6ISI: 000465216700012PubMedID: 31015488OAI: oai:DiVA.org:kau-71996DiVA, id: diva2:1314631
Available from: 2019-05-09 Created: 2019-05-09 Last updated: 2019-05-10Bibliographically approved

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Bornehag, Carl-Gustaf

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