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Insulin-Like Factor 3 Levels in Second-Trimester Amniotic Fluid

Departments of Growth and Reproduction (K.B., N.E.S., A.-M.A.), of Fetal Medicine (C.J.), and of Clinical Genetics (A.M.L.), University Hospital of Copenhagen, Rigshospitalet, DK-2100 Copenhagen, Denmark; Department of Clinical Biochemistry (A.S.C.), Statens Serum Institute, DK-2300 Copenhagen, Denmark; and Department of Obstetrics and Gynecology (F.S.J.), Fetal Medicine Unit, University Hospital of Copenhagen, Hvidovre Hospital, DK-2650 Hvidovre, Denmark

Address all correspondence and requests for reprints to: Anna-Maria Andersson, University Department of Growth and Reproduction, Rigshospitalet, GR 5064, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. E-mail: anna{at}rh.dk.

Background: According to animal studies, the testicular Leydig cell hormone insulin-like factor 3 (Insl3) exerts a fundamental role in abdominal testis translocation, which occurs in the beginning of the second trimester in humans. Despite this, human prenatal INSL3 production has been poorly investigated.

Methods: Amniotic fluid from 91 pregnant women undergoing amniocentesis was analyzed for INSL3 and testosterone (T) levels. Data were related to gestational age (15–25 wk) at amniocentesis and to sex (45 males and 48 females).

Results: INSL3 was present in amniotic fluid from all but one of the investigated male fetuses (range: <0.02–0.36 ng/ml; mean ± SD: 0.12 ± 0.07), whereas the hormone was undetectable in the female fetuses. T was significantly higher in male (range: 0.54–1.71 nmol/liter; mean ± SD: 1.04 ± 0.30) as compared with in female amniotic fluid (range: 0.19–0.50 nmol/liter; mean ± SD: 0.34 ± 0.06) (P < 0.001). In males there was no correlation between INSL3 and T. A statistically borderline negative association was found between INSL3 and gestational age (P = 0.07), whereas the corresponding association was not significant for T (P = 0.12). In contrast, T in females correlated positively with gestational age (P = 0.02).

Conclusions: INSL3 is clearly present in human male amniotic fluid in the second trimester, where abdominal testis translocation takes place. In contrast, the hormone is undetectable in female amniotic fluid. The prenatal presence of INSL3 supports the hypothesis that this hormone is essential for testicular descent in humans.