ArticleScientific reports2016
Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The Copenhagen Analgesic Study
Neurobehavioral Development in Toddlers and Preschoolers in Relation to Prenatal Exposure of Mild Analgesics
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Pooled 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
- Article
- Prevalence and predictors of analgesic use during early pregnancy in a Brazilian population.Frontiers in pharmacology · 2026Article
- Fetal exposure to paracetamol is associated with altered markers of ovarian development and reduced uterine volume in girls: the COPANA study.Human reproduction open · 2026Article
- Endocrine-disrupting chemicals and female reproductive health: a growing concern.Nature reviews. Endocrinology · 2025Review
- AOP Report: Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia.Current research in toxicology · 2025Article
- Beyond defence: Immune architects of ovarian health and disease.Seminars in immunopathology · 2024Review
- Enhanced identification of endocrine disruptors through integration of science-based regulatory practices and innovative methodologies: The MERLON Project.Open research Europe · 2024Article
- Effects and mechanisms of intrauterine chronic hypoxia on ovarian reserve function of zygotic rats.Scientific reports · 2023Article
- Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice.Neurobiology of disease · 2023Article
- Ovarian Reserve Disorders, Can We Prevent Them? A Review.International journal of molecular sciences · 2022Review
- 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
- AOP Key Event Relationship report: Linking decreased retinoic acid levels with disrupted meiosis in developing oocytes.Current research in toxicology · 2022Article
- 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
- Paracetamol use during pregnancy - a call for precautionary action.Nature reviews. Endocrinology · 2021Review
- REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond.Reproduction (Cambridge, England) · 2021Review
- Genomic and Hormonal Biomarkers of Phthalate-Induced Male Rat Reproductive Developmental Toxicity Part II: A Targeted RT-qPCR Array Approach That Defines a Unique Adverse Outcome Pathway.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Multi- and Transgenerational Outcomes of an Exposure to a Mixture of Endocrine-Disrupting Chemicals (EDCs) on Puberty and Maternal Behavior in the Female Rat.Environmental health perspectives · 2021Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development and reproductive function in resulting offspring (F1) or in the F2 generation. Exposure to either analgesic reduced F1 fetal GC number in both sexes and altered the tempo of fetal GC development sex-dependently, with delayed meiotic entry in oogonia but accelerated GC differentiation in males. These effects persisted in adult F1 females as reduced ovarian and litter size, whereas F1 males recovered normal GC numbers and fertility by adulthood. F2 offspring deriving from an analgesic-exposed F1 parent also exhibited sex-specific changes. F2 males exhibited normal reproductive development whereas F2 females had smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise concerns that analgesic use in pregnancy could potentially affect fertility of resulting daughters and grand-daughters.
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What OpenQuestion holds
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.