TY - JOUR
T1 - Loss of Insl3
T2 - A Potential Predisposing Factor for Testicular Torsion
AU - Sozubir, Selami
AU - Barber, Theodore
AU - Wang, Yi
AU - Ahn, Chul
AU - Zhang, Shaohua
AU - Verma, Sunita
AU - Lonergan, Devin
AU - Lorenzo, Armando J.
AU - Nef, Serge
AU - Baker, Linda A.
PY - 2010/6
Y1 - 2010/6
N2 - Purpose: The testicular hormone Insl3 is critical for mouse gubernacular development. Knockout mice exhibit bilateral intra-abdominal cryptorchidism with absent gubernaculum. Prior studies described torsion of the vas deferens in Insl3 mutant mice. We performed a detailed anatomical analysis of the vas deferens and testis in Insl3 mutant mice to characterize associated anomalies further. Materials and Methods: Insl3 wild-type (Insl3+/+), heterozygous (Insl3+/-) and knockout (Insl3-/-) male mice were examined either prepubertally (postnatal day 23) or in adulthood (postnatal day 90 or later). The macroscopic appearance, characteristics, and mobility of the testes and spermatic cord were recorded. Results: We examined 56 prepubertal and 33 adult mice (175 testes, 28 [20:8] Insl3+/+, 97 [60:37] Insl3+/-, 50 [32:18] Insl3-/-). Unlike normal Insl3+/+ testes, 94% of Insl3-/- testes were located intra-abdominally at all ages. Delayed descent occurred in Insl3+/- testes, since 37% of postnatal day 23 and 8% of P90 or later testes were intra-abdominal. Vas elongation/convolution and spermatic cord twisting were noted in 65% of Insl3-/-, 27% of Insl3+/- and 0% of Insl3+/+ testes. While all Insl3+/+ testes were normal, 5% of Insl3+/- and 32% of Insl3-/- testes showed significant testicular pathology, including torsion, atrophy and vanished testis, which statistically increased with age. Conclusions: Poorly formed gubernacula and increased testicular mobility in Insl3 mutant mice result in spermatic cord anomalies, delayed/absent testicular descent and subsequent testicular torsion in a gene dose dependent manner. Prepubertal testicular torsion in the mutant mice predisposes to testicular atrophy and vanishing testes in adulthood. Thus, Insl3 is a candidate signaling molecule in human delayed testicular descent and torsion.
AB - Purpose: The testicular hormone Insl3 is critical for mouse gubernacular development. Knockout mice exhibit bilateral intra-abdominal cryptorchidism with absent gubernaculum. Prior studies described torsion of the vas deferens in Insl3 mutant mice. We performed a detailed anatomical analysis of the vas deferens and testis in Insl3 mutant mice to characterize associated anomalies further. Materials and Methods: Insl3 wild-type (Insl3+/+), heterozygous (Insl3+/-) and knockout (Insl3-/-) male mice were examined either prepubertally (postnatal day 23) or in adulthood (postnatal day 90 or later). The macroscopic appearance, characteristics, and mobility of the testes and spermatic cord were recorded. Results: We examined 56 prepubertal and 33 adult mice (175 testes, 28 [20:8] Insl3+/+, 97 [60:37] Insl3+/-, 50 [32:18] Insl3-/-). Unlike normal Insl3+/+ testes, 94% of Insl3-/- testes were located intra-abdominally at all ages. Delayed descent occurred in Insl3+/- testes, since 37% of postnatal day 23 and 8% of P90 or later testes were intra-abdominal. Vas elongation/convolution and spermatic cord twisting were noted in 65% of Insl3-/-, 27% of Insl3+/- and 0% of Insl3+/+ testes. While all Insl3+/+ testes were normal, 5% of Insl3+/- and 32% of Insl3-/- testes showed significant testicular pathology, including torsion, atrophy and vanished testis, which statistically increased with age. Conclusions: Poorly formed gubernacula and increased testicular mobility in Insl3 mutant mice result in spermatic cord anomalies, delayed/absent testicular descent and subsequent testicular torsion in a gene dose dependent manner. Prepubertal testicular torsion in the mutant mice predisposes to testicular atrophy and vanishing testes in adulthood. Thus, Insl3 is a candidate signaling molecule in human delayed testicular descent and torsion.
KW - Leydig insulin-like protein
KW - cryptorchidism
KW - models, animal
KW - spermatic cord torsion
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U2 - 10.1016/j.juro.2010.02.2390
DO - 10.1016/j.juro.2010.02.2390
M3 - Article
C2 - 20400152
AN - SCOPUS:77951879259
SN - 0022-5347
VL - 183
SP - 2373
EP - 2379
JO - Journal of Urology
JF - Journal of Urology
IS - 6
ER -