ArticleFrontiers in physiology2018
Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case-Control Study.
Article in Frontiers in physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Night work during pregnancy and risk of cryptorchidism among male offspring: A Danish nationwide register-based cohort study.Andrology · 2026Article
- Foetal Exposure to Phthalates and Endocrine Effects on the Leydig Cell.Basic & clinical pharmacology & toxicology · 2025Review
- New Insights into the Role of INSL-3 in the Development of Cryptorchidism.Children (Basel, Switzerland) · 2023Review
- Association Between Proton Pump Inhibitor Use During Early Pregnancy and Risk of Congenital Malformations.JAMA network open · 2023Article
- The adverse role of endocrine disrupting chemicals in the reproductive system.Frontiers in endocrinology · 2023Review
- Maternal Age and Behavior during Pregnancy Affect the 2D:4D Digit Ratio in Polish Children Aged 6-13 Years.Biology · 2022Article
- The effects of radiofrequency exposure on male fertility and adverse reproductive outcomes: A protocol for two systematic reviews of human observational studies with meta-analysis.Environment international · 2022Article
- Expression and Role of INSL3 in the Fetal Testis.Frontiers in endocrinology · 2022Review
- REPRODUCTIVE TOXICOLOGY: Environmental exposures, fetal testis development and function: phthalates and beyond.Reproduction (Cambridge, England) · 2021Review
- Endocrine Disrupting Chemicals and Reproductive Health in Boys and Men.Frontiers in endocrinology · 2021Review
- Endocrine disrupting chemicals in the pathogenesis of hypospadias; developmental and toxicological perspectives.Current research in toxicology · 2021Review
- The Physiology of Reproduction -Frontiers in physiology · 2021Review
- Endocrine disrupting chemicals and reproductive disorders in women, men, and animal models.Advances in pharmacology (San Diego, Calif.) · 2021Article
- Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals.Archives of toxicology · 2020Review
- Phthalate-Induced Fetal Leydig Cell Dysfunction Mediates Male Reproductive Tract Anomalies.Frontiers in pharmacology · 2019Review
- Insulin-Like Peptide 3 (INSL3) Serum Concentration During Human Male Fetal Life.Frontiers in endocrinology · 2019Article
- Postnatal Testicular Activity in Healthy Boys and Boys With Cryptorchidism.Frontiers in endocrinology · 2019Review
- Biomonitoring and Subsequent Risk Assessment of Combined Exposure to Phthalates in Iranian Children and Adolescents.International journal of environmental research and public health · 2018Article
- Perspective: A Neuro-Hormonal Systems Approach to Understanding the Complexity of Cryptorchidism Susceptibility.Frontiers in endocrinology · 2018Article
- Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion: a case-control study.Sao Paulo medical journal = Revista paulista de medicinaArticle
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The period of the first to second trimester transition in human pregnancy represents a sensitive window for fetal organogenesis, particularly in regard to the development of the male reproductive system. This is a time of relative analytical inaccessibility. We have used a large national biobank of amniotic fluid samples collected at routine amniocentesis to determine the impacts of exogenous endocrine disruptor load on specific fetal biomarkers at this critical time. While adrenal and testicular steroids are highly correlated, they are also mostly positively influenced by increasing phthalate load, represented by the metabolites 7cx-MMeHP and 5cx-MEPP, by perfluorooctane sulfonate (PFOS) exposure, and by smoking, suggesting an adrenal stress response. In contrast, the testis specific biomarkers insulin-like peptide 3 (INSL3) and androstenedione are negatively impacted by the phthalate endocrine disruptors. Using a case-control design, we show that cryptorchidism and hypospadias are both significantly associated with increased amniotic concentration of INSL3 during gestational weeks 13-16, and some, though not all steroid biomarkers. Cases are also linked to a specifically increased variance in the Leydig cell biomarker INSL3 compared to controls, an effect exacerbated by maternal smoking. No influence of phthalate metabolites or PFOS was evident on the distribution of cases and controls. Considering that several animal and human studies have shown a negative impact of phthalate load on fetal and cord blood INSL3, respectively, the present results suggest that such endocrine disruptors may rather be altering the relative dynamics of testicular development and consequent hormone production, leading to a desynchronization of tissue organization during fetal development. Being born small for gestational age appears not to impact on the testicular biomarker INSL3 in second trimester amniotic fluid.
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