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Amniotic fluid phthalate levels and male fetal gonad function.

https://arctichealth.org/en/permalink/ahliterature264835
Source
Epidemiology. 2015 Jan;26(1):91-9
Publication Type
Article
Date
Jan-2015
Author
Morten Søndergaard Jensen
Ravinder Anand-Ivell
Bent Nørgaard-Pedersen
Bo A G Jönsson
Jens Peter Bonde
David M Hougaard
Arieh Cohen
Christian H Lindh
Richard Ivell
Gunnar Toft
Source
Epidemiology. 2015 Jan;26(1):91-9
Date
Jan-2015
Language
English
Publication Type
Article
Keywords
Adult
Amniotic Fluid - chemistry
Case-Control Studies
Cryptorchidism - epidemiology
Denmark - epidemiology
Diethylhexyl Phthalate - analysis
Environmental Exposure - statistics & numerical data
Female
Gonadal Steroid Hormones - analysis
Humans
Hydrocortisone - analysis
Hypospadias - epidemiology
Immunoassay
Infant, Newborn
Insulin - analysis
Leydig Cells
Linear Models
Logistic Models
Male
Mass Spectrometry
Phthalic Acids - analysis
Pregnancy
Proteins - analysis
Abstract
Prenatal exposure to phthalates may pose a threat to human male reproduction. However, additional knowledge about the in vivo effect in humans is needed, and reported associations with genital abnormalities are inconclusive. We aimed to study prenatal di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP) exposure in relation to cryptorchidism, hypospadias, and human fetal Leydig cell function.
We studied 270 cryptorchidism cases, 75 hypospadias cases, and 300 controls. Second-trimester amniotic fluid samples were available from a Danish pregnancy-screening biobank (n = 25,105) covering 1980-1996. We assayed metabolites of DEHP and DiNP (n = 645) and steroid hormones (n = 545) by mass spectrometry. We assayed insulin-like factor 3 by immunoassay (n = 475) and analyzed data using linear or logistic regression.
Mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP, DEHP metabolite) was not consistently associated with cryptorchidism or hypospadias. However, we observed an 18% higher (95% confidence interval [CI] = 5%-33%) testosterone level, and a 41% lower (-56% to -21%) insulin-like factor 3 level in the highest 5cx-MEPP tertile compared with the lowest. Mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP, DiNP metabolite) showed elevated odds ratio point estimates for having cryptorchidism (odds ratio = 1.28 [95% CI = 0.80 to 2.01]) and hypospadias (1.69 [0.78 to 3.67]), but was not consistently associated with the steroid hormones or insulin-like factor 3.
Data on the DEHP metabolite indicate possible interference with human male fetal gonadal function. Considering the DiNP metabolite, we cannot exclude (nor statistically confirm) an association with hypospadias and, less strongly, with cryptorchidism.
PubMed ID
25384265 View in PubMed
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The association between circulating levels of antim├╝llerian hormone and follicle number, androgens, and menstrual cycle characteristics in young women.

https://arctichealth.org/en/permalink/ahliterature127997
Source
Fertil Steril. 2012 Mar;97(3):779-85
Publication Type
Article
Date
Mar-2012
Author
Susanne Lund Kristensen
Cecilia Høst Ramlau-Hansen
Claus Yding Andersen
Erik Ernst
Sjurdur Frodi Olsen
Jens Peter Bonde
Anne Vested
Gunnar Toft
Author Affiliation
Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. susankst@rm.dk
Source
Fertil Steril. 2012 Mar;97(3):779-85
Date
Mar-2012
Language
English
Publication Type
Article
Keywords
Age Factors
Anti-Mullerian Hormone - blood
Biological Markers - blood
Contraceptive Agents, Female - therapeutic use
Denmark
Female
Hospitals, University
Humans
Linear Models
Menstrual Cycle - blood - drug effects
Ovarian Follicle - drug effects - metabolism - ultrasonography
Reproduction
Testosterone - blood
Young Adult
Abstract
To investigate the association between serum antim?llerian hormone (AMH) and other reproductive parameters in young women.
Cross-sectional study.
University hospital.
Population-based cohort of 256 women: 180 were users and 76 were nonusers of hormonal contraceptives.
None.
Antral follicles, androgens, age at menarche, and duration and regularity of menstrual cycle.
AMH levels were lower among users of hormonal contraceptives compared to nonusers. Among nonusers, women with AMH levels in the upper tertile had 55% (95% confidence interval [CI]: 22%-99%) higher levels of total T and 8% (95% CI = 2%-15%) longer menstrual cycles than women with AMH levels in the lower tertile. An increase of 1 ng/mL in AMH was associated with 45% (95% CI = 6%-97%) higher prevalence of irregular menstrual cycles. These associations were not seen among users of hormonal contraceptives. A strong relationship between AMH and follicle number was found in both users and nonusers.
AMH measurements were found to be applicable in evaluation of the reproductive function of young women. However, there may be differences in the way that serum AMH levels can be interpreted depending on whether the woman uses hormonal contraceptives or not.
PubMed ID
22244782 View in PubMed
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Associations of in utero exposure to perfluorinated alkyl acids with human semen quality and reproductive hormones in adult men.

https://arctichealth.org/en/permalink/ahliterature116786
Source
Environ Health Perspect. 2013 Apr;121(4):453-8, 458e1-5
Publication Type
Article
Date
Apr-2013
Author
Anne Vested
Cecilia Høst Ramlau-Hansen
Sjurdur Frodi Olsen
Jens Peter Bonde
Susanne Lund Kristensen
Thorhallur Ingi Halldorsson
Georg Becher
Line Småstuen Haug
Emil Hagen Ernst
Gunnar Toft
Author Affiliation
Danish Ramazzini Centre, Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. anneveed@rm.dk
Source
Environ Health Perspect. 2013 Apr;121(4):453-8, 458e1-5
Date
Apr-2013
Language
English
Publication Type
Article
Keywords
Alkanesulfonic Acids - blood
Caprylates - blood
Chromatography, Liquid
Cohort Studies
Denmark - epidemiology
Endocrine Disruptors - blood
Environmental Exposure
Female
Fluorocarbons - blood
Gonadal Steroid Hormones - blood
Humans
Linear Models
Luminescent Measurements
Male
Pregnancy
Prenatal Exposure Delayed Effects - chemically induced - epidemiology
Prospective Studies
Semen - drug effects - physiology
Semen Analysis
Sperm Count
Tandem Mass Spectrometry
Testis - anatomy & histology - drug effects
Young Adult
Abstract
Perfluorinated alkyl acids (PFAAs), persistent chemicals with unique water-, dirt-, and oil-repellent properties, are suspected of having endocrine-disrupting activity. The PFAA compounds perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are found globally in humans; because they readily cross the placental barrier, in utero exposure may be a cause for concern.
We investigated whether in utero exposure to PFOA and PFOS affects semen quality, testicular volume, and reproductive hormone levels.
We recruited 169 male offspring (19-21 years of age) from a pregnancy cohort established in Aarhus, Denmark, in 1988-1989, corresponding to 37.6% of the eligible sons. Each man provided a semen sample and a blood sample. Semen samples were analyzed for sperm concentration, total sperm count, motility, and morphology, and blood samples were used to measure reproductive hormones. As a proxy for in utero exposure, PFOA and PFOS were measured in maternal blood samples from pregnancy week 30.
Multivariable linear regression analysis suggested that in utero exposure to PFOA was associated with lower adjusted sperm concentration (ptrend = 0.01) and total sperm count (ptrend = 0.001) and with higher adjusted levels of luteinizing hormone (ptrend = 0.03) and follicle-stimulating hormone (ptrend = 0.01). PFOS did not appear to be associated with any of the outcomes assessed, before or after adjustment.
The results suggest that in utero exposure to PFOA may affect adult human male semen quality and reproductive hormone levels.
Notes
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PubMed ID
23360585 View in PubMed
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Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal trends and timing of amniocentesis in pregnancy.

https://arctichealth.org/en/permalink/ahliterature126355
Source
Environ Health Perspect. 2012 Jun;120(6):897-903
Publication Type
Article
Date
Jun-2012
Author
Morten Søndergaard Jensen
Bent Nørgaard-Pedersen
Gunnar Toft
David M Hougaard
Jens Peter Bonde
Arieh Cohen
Ane Marie Thulstrup
Richard Ivell
Ravinder Anand-Ivell
Christian H Lindh
Bo A G Jönsson
Author Affiliation
Danish Ramazzini Centre, Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. morten@sondergaard-jensen.dk
Source
Environ Health Perspect. 2012 Jun;120(6):897-903
Date
Jun-2012
Language
English
Publication Type
Article
Keywords
Alkanesulfonic Acids - analysis
Amniocentesis - methods
Amniotic Fluid - chemistry
Chromatography, Liquid
Denmark
Environmental Pollutants - analysis
Female
Fluorocarbons - analysis
Gestational Age
Humans
Linear Models
Male
Mass Spectrometry
Maternal Exposure - statistics & numerical data
Phthalic Acids - analysis
Pregnancy
Abstract
Measures of prenatal environmental exposures are important, and amniotic fluid levels may directly reflect fetal exposures during hypothesized windows of vulnerability.
We aimed to detect various phthalate metabolites and perfluorooctanesulfonic acid (PFOS) in human amniotic fluid, to study temporal exposure trends, and to estimate potential associations with gestational week of amniocentesis and maternal age and parity at amniocentesis.
We studied 300 randomly selected second-trimester amniotic fluid samples from a Danish pregnancy-screening biobank covering 1980 through 1996. We used only samples from male offspring pregnancies. We assayed the environmental pollutants by liquid chromatography/triple quadrupole mass spectrometry and analyzed data using generalized linear regression models.
We detected the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) at a median concentration of 0.27 ng/mL [interquartile range (IQR): 0.20-0.37 ng/mL], the diisononyl phthalate (DiNP) metabolite mono(4-methyl-7-carboxyheptyl) phthalate (7cx-MMeHP) at 0.07 ng/mL (IQR: 0.05-0.11 ng/mL), and PFOS at 1.1 ng/mL (IQR: 0.66-1.60 ng/mL). An increase of 1 calendar year was associated with 3.5% lower [95% confidence interval (CI): -4.8%, -2.1%] 5cx-MEPP levels and with 7.1% higher (95% CI: 5.3%, 9.0%) 7cx-MMeHP levels. For each later gestational week of amniocentesis, 5cx-MEPP was 9.9% higher (95% CI: 4.8%, 15.2%), 7cx-MMeHP was 8.6% higher (95: CI: 2.7%, 14.9%), and PFOS was 9.4% higher (95: CI: 3.3%, 15.9%). We observed no associations with maternal age or parity.
Measured metabolite levels appeared to parallel decreasing DEHP exposure and increasing DiNP exposure during the study period. The environmental pollutant levels were positively associated with later gestational age at amniocentesis during pregnancy weeks 12-22.
Notes
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PubMed ID
22398305 View in PubMed
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