About Hoxa 10 and Insl3 Genes in the DES exposed

Update on cryptorchidism : endocrine, environmental and therapeutic aspects

2003 Study Abstract

Two recently identified factors, Hoxa 10 and Insl3 (Leydig insulin-like hormone) seem to be involved in the development and action of the gubernaculum. Hoxa 10 is strongly expressed in the gubernaculum and Insl3 seems to play a key role in the abdominal phase of testis migration.

Hox genes (homeobox) are known for their important role in morphogenesis. Transgenic mice with mutated Hoxa 10 gene have an abnormally long gubernacular cord associated with intra-abdominal testis. In addition, preliminary results point to possible mutations in the exon 1 of the Hoxa 10 gene in five cryptorchid boys out of 45 studied, while polymorphism seems frequent in that gene both in controls and cryptorchid boys.

Insl3 seems to be an interesting lead. This hormone of Leydigian origin belongs to the superfamily of insulin-like hormones. Targeted invalidation of its gene in male mice causes bilateral cryptorchidism associated with developmental defect of gubernaculum. However, recent studies suggest that mutations in the Insl3 gene are likely to be rare , though a functional defect is still plausible. Interestingly, an interface between estrogens and Insl3 pathways has been shown recently. Prenatal exposure to diethylstilbestrol (DES) is a well known factor causing cryptorchidism in different animal models and in man. In addition, 100 g/kg/day of DES given to pregnant mice from day 9 to 17 prevent normal gubernaculum development and is associated with a three-fold decrease in Insl3 mRNA expression, with no change in steroidogenic factor 1 (SF1) expression.

These results are similar to those obtained with 17 -estradiol, 17 -estradiol and DES also in mice. This is the first time that such a molecular mechanism of action has been identified for estrogens.


  • Update on cryptorchidism: endocrine, environmental and therapeutic aspects NCBI PubMed PMID: 12952375, 2003 Jun.
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