Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study

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...
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Autor*in:	Ravinder Anand-Ivell [verfasserIn] Arieh Cohen [verfasserIn] Bent Nørgaard-Pedersen [verfasserIn] Bo A. G. Jönsson [verfasserIn] Jens-Peter Bonde [verfasserIn] David M. Hougaard [verfasserIn] Christian H. Lindh [verfasserIn] Gunnar Toft [verfasserIn] Morten S. Lindhard [verfasserIn] Richard Ivell [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2018

Schlagwörter:	INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate

Übergeordnetes Werk:	In: Frontiers in Physiology - Frontiers Media S.A., 2011, 9(2018)
Übergeordnetes Werk:	volume:9 ; year:2018

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphys.2018.00406

Katalog-ID:	DOAJ073552399

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allfields	10.3389/fphys.2018.00406 doi (DE-627)DOAJ073552399 (DE-599)DOAJcec7d9e52f8b4bef9e1d3f897524928d DE-627 ger DE-627 rakwb eng QP1-981 Ravinder Anand-Ivell verfasserin aut Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate Physiology Arieh Cohen verfasserin aut Bent Nørgaard-Pedersen verfasserin aut Bo A. G. Jönsson verfasserin aut Jens-Peter Bonde verfasserin aut David M. Hougaard verfasserin aut Christian H. Lindh verfasserin aut Gunnar Toft verfasserin aut Morten S. Lindhard verfasserin aut Richard Ivell verfasserin aut Richard Ivell verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 9(2018) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:9 year:2018 https://doi.org/10.3389/fphys.2018.00406 kostenfrei https://doaj.org/article/cec7d9e52f8b4bef9e1d3f897524928d kostenfrei http://journal.frontiersin.org/article/10.3389/fphys.2018.00406/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
spelling	10.3389/fphys.2018.00406 doi (DE-627)DOAJ073552399 (DE-599)DOAJcec7d9e52f8b4bef9e1d3f897524928d DE-627 ger DE-627 rakwb eng QP1-981 Ravinder Anand-Ivell verfasserin aut Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate Physiology Arieh Cohen verfasserin aut Bent Nørgaard-Pedersen verfasserin aut Bo A. G. Jönsson verfasserin aut Jens-Peter Bonde verfasserin aut David M. Hougaard verfasserin aut Christian H. Lindh verfasserin aut Gunnar Toft verfasserin aut Morten S. Lindhard verfasserin aut Richard Ivell verfasserin aut Richard Ivell verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 9(2018) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:9 year:2018 https://doi.org/10.3389/fphys.2018.00406 kostenfrei https://doaj.org/article/cec7d9e52f8b4bef9e1d3f897524928d kostenfrei http://journal.frontiersin.org/article/10.3389/fphys.2018.00406/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfields_unstemmed	10.3389/fphys.2018.00406 doi (DE-627)DOAJ073552399 (DE-599)DOAJcec7d9e52f8b4bef9e1d3f897524928d DE-627 ger DE-627 rakwb eng QP1-981 Ravinder Anand-Ivell verfasserin aut Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate Physiology Arieh Cohen verfasserin aut Bent Nørgaard-Pedersen verfasserin aut Bo A. G. Jönsson verfasserin aut Jens-Peter Bonde verfasserin aut David M. Hougaard verfasserin aut Christian H. Lindh verfasserin aut Gunnar Toft verfasserin aut Morten S. Lindhard verfasserin aut Richard Ivell verfasserin aut Richard Ivell verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 9(2018) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:9 year:2018 https://doi.org/10.3389/fphys.2018.00406 kostenfrei https://doaj.org/article/cec7d9e52f8b4bef9e1d3f897524928d kostenfrei http://journal.frontiersin.org/article/10.3389/fphys.2018.00406/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsGer	10.3389/fphys.2018.00406 doi (DE-627)DOAJ073552399 (DE-599)DOAJcec7d9e52f8b4bef9e1d3f897524928d DE-627 ger DE-627 rakwb eng QP1-981 Ravinder Anand-Ivell verfasserin aut Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate Physiology Arieh Cohen verfasserin aut Bent Nørgaard-Pedersen verfasserin aut Bo A. G. Jönsson verfasserin aut Jens-Peter Bonde verfasserin aut David M. Hougaard verfasserin aut Christian H. Lindh verfasserin aut Gunnar Toft verfasserin aut Morten S. Lindhard verfasserin aut Richard Ivell verfasserin aut Richard Ivell verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 9(2018) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:9 year:2018 https://doi.org/10.3389/fphys.2018.00406 kostenfrei https://doaj.org/article/cec7d9e52f8b4bef9e1d3f897524928d kostenfrei http://journal.frontiersin.org/article/10.3389/fphys.2018.00406/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
allfieldsSound	10.3389/fphys.2018.00406 doi (DE-627)DOAJ073552399 (DE-599)DOAJcec7d9e52f8b4bef9e1d3f897524928d DE-627 ger DE-627 rakwb eng QP1-981 Ravinder Anand-Ivell verfasserin aut Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate Physiology Arieh Cohen verfasserin aut Bent Nørgaard-Pedersen verfasserin aut Bo A. G. Jönsson verfasserin aut Jens-Peter Bonde verfasserin aut David M. Hougaard verfasserin aut Christian H. Lindh verfasserin aut Gunnar Toft verfasserin aut Morten S. Lindhard verfasserin aut Richard Ivell verfasserin aut Richard Ivell verfasserin aut In Frontiers in Physiology Frontiers Media S.A., 2011 9(2018) (DE-627)631498788 (DE-600)2564217-0 1664042X nnns volume:9 year:2018 https://doi.org/10.3389/fphys.2018.00406 kostenfrei https://doaj.org/article/cec7d9e52f8b4bef9e1d3f897524928d kostenfrei http://journal.frontiersin.org/article/10.3389/fphys.2018.00406/full kostenfrei https://doaj.org/toc/1664-042X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2018
language	English
source	In Frontiers in Physiology 9(2018) volume:9 year:2018
sourceStr	In Frontiers in Physiology 9(2018) volume:9 year:2018
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate Physiology
isfreeaccess_bool	true
container_title	Frontiers in Physiology
authorswithroles_txt_mv	Ravinder Anand-Ivell @@aut@@ Arieh Cohen @@aut@@ Bent Nørgaard-Pedersen @@aut@@ Bo A. G. Jönsson @@aut@@ Jens-Peter Bonde @@aut@@ David M. Hougaard @@aut@@ Christian H. Lindh @@aut@@ Gunnar Toft @@aut@@ Morten S. Lindhard @@aut@@ Richard Ivell @@aut@@
publishDateDaySort_date	2018-01-01T00:00:00Z
hierarchy_top_id	631498788
id	DOAJ073552399
language_de	englisch
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callnumber-first	Q - Science
author	Ravinder Anand-Ivell
spellingShingle	Ravinder Anand-Ivell misc QP1-981 misc INSL3 misc amniotic fluid misc fetal steroids misc cryptorchidism misc hypospadias misc phthalate misc Physiology 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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topic_title	QP1-981 Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study INSL3 amniotic fluid fetal steroids cryptorchidism hypospadias phthalate
topic	misc QP1-981 misc INSL3 misc amniotic fluid misc fetal steroids misc cryptorchidism misc hypospadias misc phthalate misc Physiology
topic_unstemmed	misc QP1-981 misc INSL3 misc amniotic fluid misc fetal steroids misc cryptorchidism misc hypospadias misc phthalate misc Physiology
topic_browse	misc QP1-981 misc INSL3 misc amniotic fluid misc fetal steroids misc cryptorchidism misc hypospadias misc phthalate misc Physiology
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title	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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title_full	Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study
author_sort	Ravinder Anand-Ivell
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author_browse	Ravinder Anand-Ivell Arieh Cohen Bent Nørgaard-Pedersen Bo A. G. Jönsson Jens-Peter Bonde David M. Hougaard Christian H. Lindh Gunnar Toft Morten S. Lindhard Richard Ivell
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title_sort	amniotic fluid insl3 measured during the critical time window in human pregnancy relates to cryptorchidism, hypospadias, and phthalate load: a large case–control study
callnumber	QP1-981
title_auth	Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study
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.
abstractGer	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.
abstract_unstemmed	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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title_short	Amniotic Fluid INSL3 Measured During the Critical Time Window in Human Pregnancy Relates to Cryptorchidism, Hypospadias, and Phthalate Load: A Large Case–Control Study
url	https://doi.org/10.3389/fphys.2018.00406 https://doaj.org/article/cec7d9e52f8b4bef9e1d3f897524928d http://journal.frontiersin.org/article/10.3389/fphys.2018.00406/full https://doaj.org/toc/1664-042X
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author2	Arieh Cohen Bent Nørgaard-Pedersen Bo A. G. Jönsson Jens-Peter Bonde David M. Hougaard Christian H. Lindh Gunnar Toft Morten S. Lindhard Richard Ivell
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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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