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The Journal of clinical endocrinology and metabolism
09, 2016;101 (9): 3378-85.

Thyroid Hormone Status in Umbilical Cord Serum Is Positively Associated with Male Anogenital Distance.

Rongju Liu, Xijin Xu, Yuling Zhang, Xiangbin Zheng, Stephani S Kim, Kim N Dietrich, Shuk-Mei Ho, Tiina Reponen, Aimin Chen, Xia Huo
Author Information
  1. Rongju Liu: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  2. Xijin Xu: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  3. Yuling Zhang: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  4. Xiangbin Zheng: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  5. Stephani S Kim: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  6. Kim N Dietrich: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  7. Shuk-Mei Ho: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  8. Tiina Reponen: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  9. Aimin Chen: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
  10. Xia Huo: Laboratory of Environmental Medicine and Developmental Toxicology (R.L., X.X., Y.Z., X.Z., X.H.), and Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Obstetrics and Gynecology (R.L.), The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics (X.X.), Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Environmental Health (S.S.K., K.N.D., S.-M.H., T.R., A.C.), College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; and School of Environment (X.H.), Guangzhou Key Laboratory of Environmental Exposure and Health, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China.
PMID: 27383112 DOI: 10.1210/jc.2015-3872

Abstract

CONTEXT: In human adults and adolescents, thyroid function affects sex hormones and male reproductive functions. Little is known about the thyroid function effects on the gonadal development in human infants.
OBJECTIVE: The aim was to examine the association between thyroid hormones (THs) and sexually dimorphic genital development or fetal growth.
DESIGN: This is a birth cohort study.
PARTICIPANTS: A total of 616 mothers and newborns were analyzed from two local hospitals.
MAIN OUTCOME MEASURES: TSH, free T3 (FT3), and free T4 (FT4) levels in cord blood serum, anogenital distance (AGD), birth weight, birth length, birth body mass index, and head circumference in neonates.
RESULTS: Longer AGD in male newborns was observed with higher cord serum FT3 (β, 1.36 mm [95% confidence interval (CI), 0.58-2.13] for 1 pmol/L FT3), FT4 (β, 0.12 mm [95% CI, 0.00-0.25] for 1 pmol/L FT4), and TSH (β, 3.14 mm [95% CI, 0.65-5.63] for a 10-fold TSH increase), and with a lower FT4/FT3 ratio (β, -0.11 mm [95% CI, -0.20 to -0.02] for doubling FT4/FT3 ratio). The relationships between TSH, birth weight, and birth length were different by secondhand smoke exposure. Secondhand smoke exposure had an effect modification, with interaction P value .039 and .010, respectively. Secondhand smoke exposure also had an effect modification on the relation between FT4 and head circumference with interaction P value .020.
CONCLUSIONS: In the absence of overt thyroid dysfunction, THs are positively associated with AGD in male newborns. TH effects on body size and head circumference may be modified by maternal secondhand smoke exposure.

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Grants

  1. P30 ES006096/NIEHS NIH HHS
  2. RC4 ES019755/NIEHS NIH HHS

MeSH Term

Adolescent
Adult
Biomarkers
Birth Weight
Cohort Studies
Female
Fetal Blood
Fetal Development
Follow-Up Studies
Gonads
Humans
Infant, Newborn
Male
Mothers
Organ Size
Prognosis
Testis
Thyroid Function Tests
Thyroid Hormones

Chemicals

Biomarkers
Thyroid Hormones
Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0birththyroidTSHFT4βmm[95%CI0smokeexposuremalenewbornsFT3AGDheadcircumference1-0humanfunctionhormoneseffectsdevelopmentTHsfreecordserumweightlengthbodypmol/LFT4/FT3ratiosecondhandSecondhandeffectmodificationinteractionPvalueCONTEXT:adultsadolescentsaffectssexreproductivefunctionsLittleknowngonadalinfantsOBJECTIVE:aimexamineassociationsexuallydimorphicgenitalfetalgrowthDESIGN:cohortstudyPARTICIPANTS:total616mothersanalyzedtwolocalhospitalsMAINOUTCOMEMEASURES:T3T4levelsbloodanogenitaldistancemassindexneonatesRESULTS:Longerobservedhigher36confidenceinterval58-213]1200-025]31465-563]10-foldincreaselower112002]doublingrelationshipsdifferent039010respectivelyalsorelation020CONCLUSIONS:absenceovertdysfunctionpositivelyassociatedTHsizemaymodifiedmaternalThyroidHormoneStatusUmbilicalCordSerumPositivelyAssociatedMaleAnogenitalDistance

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