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Hum. Reprod. Advance Access published online on February 29, 2008

Human Reproduction, doi:10.1093/humrep/den038
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Insulin-like factor 3 levels in amniotic fluid of human male fetuses

Ravinder Anand-Ivell1, Richard Ivell1,4, Deborah Driscoll2 and Jeanne Manson3

1 School of Molecular and Biomedical Science, University of Adelaide, Adelaide, 5005 SA, Australia 2 Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA 3 Division of Human Genetics and Molecular Biology, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA

4 Correspondence address. E-mail: richard.ivell{at}adelaide.edu.au

BACKGROUND: Rodent studies suggest that the peptide hormone insulin-like factor 3 (Insl3) made by the fetal testis is responsible for the first transabdominal phase of testicular descent, and may be affected by xenobiotics to disrupt male reproductive tract development. To date, there is very little information on the production of INSL3 by the human fetus during gestation. The objective of the present study was to determine the concentrations and time course during pregnancy of INSL3 and testosterone production in human fetuses and their associations with maternal characteristics, pregnancy complications and outcome.

METHODS: This is a retrospective cohort study in which women who contributed amniotic fluid specimens to a bank from 2003–2006 were followed to determine their pregnancy complications and pregnancy outcome. Amniotic fluid specimens were collected from the Reproductive Genetics Laboratory of the Hospital of the University of Pennsylvania subsequent to routine amniocentesis. INSL3 and total testosterone levels were measured in amniotic fluid (from n = 50 female, n = 237 male fetuses) by validated immunoassays and correlated with maternal characteristics, pregnancy complications and outcomes.

RESULTS: INSL3 was only detectable in amniotic fluid from male fetuses, and highest levels occurred from weeks 15–17 of gestation. INSL3 concentration was positively associated with increased birth weight, the occurrence of pre-eclampsia and advanced maternal age, but not with testosterone levels.

CONCLUSIONS: INSL3 concentration in human amniotic fluid is potentially predictive of fetal sex and pre-eclampsia, and presumably reflects the functioning of the fetal Leydig cell population.

Key words: insulin-like factor 3/amniotic fluid/sex determination/pre-eclampsia

Submitted on August 2, 2007; resubmitted on December 8, 2007; accepted on January 26, 2008.


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