ArticleScience translational medicine2015
Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
54 citing papers in PubMed, 4 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- Integrative Bioinformatic and Epidemiological Analysis of Acetaminophen Use and Risk of Sex Hormone-Related Cancers.International journal of molecular sciences · 2025Pooled it
- Effects of major analgesics on male fertility: A systematic literature review.JBRA assisted reproduction · 2024Pooled it
- Impacts of platinum-based chemotherapy on subsequent testicular function and fertility in boys with cancer.Human reproduction update · 2020Pooled 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
- Genetic, Epigenetic, and Non-Genetic Factors in Testicular Dysgenesis Syndrome: A Narrative Review.Genes · 2025Review
- Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement.Endocrine reviews · 2024Review
- Higher paracetamol levels are associated with elevated glucocorticoid concentrations in hair: findings from a large cohort of young adults.Archives of toxicology · 2024Article
- Article
- Review
- Mitochondrial oxidative damage by co-exposure to bisphenol A and acetaminophen in rat testes and its amelioration by melatonin.Clinical and experimental reproductive medicine · 2023Article
- Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy.Acta pharmaceutica Sinica. B · 2023Review
- Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice.Neurobiology of disease · 2023Article
- Global patterns in testicular cancer incidence and mortality in 2020.International journal of cancer · 2022Article
- Acetaminophen (APAP, Paracetamol) Interferes With the First Trimester Human Fetal Ovary Development in an Ex Vivo Model.The Journal of clinical endocrinology and metabolism · 2022Article
- Maternal Paracetamol Intake During Pregnancy-Impacts on Offspring Reproductive Development.Frontiers in toxicology · 2022Review
- Using Experimental Models to Decipher the Effects of Acetaminophen and NSAIDs on Reproductive Development and Health.Frontiers in toxicology · 2022Review
- Eicosanoid Biosynthesis in Male Reproductive Development: Effects of Perinatal Exposure to NSAIDs and Analgesic Drugs.Frontiers in toxicology · 2022Review
- Cisplatin Effects on the Human Fetal Testis - Establishing the Sensitive Period for (Pre)Spermatogonial Loss and Relevance for Fertility Preservation in Pre-Pubertal Boys.Frontiers in endocrinology · 2022Article
- Paracetamol use during pregnancy - a call for precautionary action.Nature reviews. Endocrinology · 2021Review
- Six Decades of Research on Human Fetal Gonadal Steroids.International journal of molecular sciences · 2021Review
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Authors and funding
13 authors at 2 institutions in 2 countries.
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Abstract
Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect.
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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.