ArticleScientific reports2017
Ibuprofen results in alterations of human fetal testis development.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.
- Effects of major analgesics on male fertility: A systematic literature review.JBRA assisted reproduction · 2024Pooled it
- Effect of environmental and pharmaceutical exposures on fetal testis development and function: a systematic review of human experimental data.Human reproduction update · 2019Pooled it
- Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.Proceedings of the National Academy of Sciences of the United States of America · 2018Trial
- Naproxen and Ibuprofen Exposure Alter the Blood-Testis Barrier in a Novel In Vitro Model.International journal of molecular sciences · 2026Article
- Prevalence and predictors of analgesic use during early pregnancy in a Brazilian population.Frontiers in pharmacology · 2026Article
- Building a human pluripotent stem cell-based gonadal niche: improving in vitro systems with in vivo insights.Human reproduction update · 2025Review
- The Effect of Hydroalcoholic Extract ofFood science & nutrition · 2025Article
- Expression of the endocannabinoid system and response to cannabinoid components by the human fetal testis.BMC medicine · 2023Article
- Article
- Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy.Acta pharmaceutica Sinica. B · 2023Review
- Impact of endocrine disrupting chemicals and pharmaceuticals on Sertoli cell development and functions.Frontiers in endocrinology · 2023Review
- Eicosanoid Biosynthesis in Male Reproductive Development: Effects of Perinatal Exposure to NSAIDs and Analgesic Drugs.Frontiers in toxicology · 2022Review
- Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health.Frontiers in toxicology · 2022Review
- Expression and Role of INSL3 in the Fetal Testis.Frontiers in endocrinology · 2022Review
- Pharmaceutical Pollution in Aquatic Environments: A Concise Review of Environmental Impacts and Bioremediation Systems.Frontiers in microbiology · 2022Review
- Activin A and Sertoli Cells: Key to Fetal Testis Steroidogenesis.Frontiers in endocrinology · 2022Review
- Deciphering Sex-Specific Differentiation of Human Fetal Gonads: Insight From Experimental Models.Frontiers in cell and developmental biology · 2022Review
- Six Decades of Research on Human Fetal Gonadal Steroids.International journal of molecular sciences · 2021Review
- A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells.Tissue engineering and regenerative medicine · 2021Article
- The Molecular Mechanism of Sex Hormones on Sertoli Cell Development and Proliferation.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10-12 GW, or in second trimester xenografted testes (14-17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow 'early window' of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.