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Amniotic fluid INSL...
Amniotic fluid INSL3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load : A large case-control study
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- Anand-Ivell, Ravinder (author)
- University of Nottingham
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- Cohen, Arieh (author)
- Danish Serum Institute, Copenhagen
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- Nørgaard-Pedersen, Bent (author)
- Danish Serum Institute, Copenhagen
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- Jönsson, Bo A.G. (author)
- Lund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine
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- Bonde, Jens Peter (author)
- University of Copenhagen,Bispebjerg Hospital
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- Hougaard, David M. (author)
- Danish Serum Institute, Copenhagen
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- Lindh, Christian H. (author)
- Lund University,Lunds universitet,Tillämpad masspektrometri inom miljömedicin,Forskargrupper vid Lunds universitet,Applied Mass Spectrometry in Environmental Medicine,Lund University Research Groups
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- Toft, Gunnar (author)
- Aarhus University Hospital
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- Lindhard, Morten S. (author)
- Aarhus University Hospital
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- Ivell, Richard (author)
- University of Nottingham
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(creator_code:org_t)
- 2018-04-24
- 2018
- English.
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:APR
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Keyword
- Amniotic fluid
- Cryptorchidism
- Fetal steroids
- Hypospadias
- INSL3
- PFOS
- Phthalate
- Testicular dysgenesis syndrome
Publication and Content Type
- art (subject category)
- ref (subject category)
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