Leydig insulin-like hormone, gubebnacular development and testicular descent

Purpose: Testicular descent is controlled by 2 morphological and hormonal steps. Transabdominal testicular descent is mediated by gubernacular swelling and regression of the cranial suspensory ligament. Mullerian inhibiting substance (MIS) has been proposed to stimulate the swelling but this remains controversial. Recently, a mouse mutant for Leydig insulin-like hormone (Insl3) was found to have undescended testis and deficient gubernaculum. We examine the testicular position of Insl3 mutant mice and the development of gubernacula. Materials and Methods: Mice with Insl3 homozygotes (-/-), heterozygotes (+/-) and wild-types (+/+) were examined at embryonic day 16.5 and birth. Macroscopic dissections and measurements of the testicular position, as well as microscopic analysis (hematoxylin and eosin, and Masson's trichrome) were performed. Results: Of the mice 11 Ins13 homozygote males had significantly impaired testicular descent at embryonic day 16.5 and birth (p <0.01), and the cord was thin and elongated, while 14 heterozygotes and 7 wild-types had normal testicular descent. Microscopically, the gubernaculum of Ins13 homozygotes was small with some muscle development but no central core of mesenchyme at embryonic day 16.5. On the ether hand, heterozygotes and wild-types had normal gubernacular development with a swelling reaction. Conclusions: Insl3 mutants show feminized gubernaculum with deficient mesenchymal core. Insl3 appears to have some role in the gubernacular swelling reaction in mice.