Loss of Insl3: A Potential Predisposing Factor for Testicular Torsion

Selami Sozubir, Theodore Barber, Yi Wang, Chul Ahn, Shaohua Zhang, Sunita Verma, Devin Lonergan, Armando J. Lorenzo, Serge Nef, Linda A. Baker

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2373-2379
Number of pages7
JournalJournal of Urology
Volume183
Issue number6
DOIs
StatePublished - Jun 2010

Fingerprint

Spermatic Cord Torsion
Causality
Testis
Spermatic Cord
Vas Deferens
Atrophy
Testicular Hormones
Cryptorchidism
Knockout Mice
Pathology

Keywords

  • cryptorchidism
  • Leydig insulin-like protein
  • models, animal
  • spermatic cord torsion

ASJC Scopus subject areas

  • Urology

Cite this

Loss of Insl3 : A Potential Predisposing Factor for Testicular Torsion. / Sozubir, Selami; Barber, Theodore; Wang, Yi; Ahn, Chul; Zhang, Shaohua; Verma, Sunita; Lonergan, Devin; Lorenzo, Armando J.; Nef, Serge; Baker, Linda A.

In: Journal of Urology, Vol. 183, No. 6, 06.2010, p. 2373-2379.

Research output: Contribution to journalArticle

Sozubir, S, Barber, T, Wang, Y, Ahn, C, Zhang, S, Verma, S, Lonergan, D, Lorenzo, AJ, Nef, S & Baker, LA 2010, 'Loss of Insl3: A Potential Predisposing Factor for Testicular Torsion', Journal of Urology, vol. 183, no. 6, pp. 2373-2379. https://doi.org/10.1016/j.juro.2010.02.2390
Sozubir, Selami ; Barber, Theodore ; Wang, Yi ; Ahn, Chul ; Zhang, Shaohua ; Verma, Sunita ; Lonergan, Devin ; Lorenzo, Armando J. ; Nef, Serge ; Baker, Linda A. / Loss of Insl3 : A Potential Predisposing Factor for Testicular Torsion. In: Journal of Urology. 2010 ; Vol. 183, No. 6. pp. 2373-2379.
@article{58ef3e98315f494688c1f8123c03f076,
title = "Loss of Insl3: A Potential Predisposing Factor for Testicular Torsion",
abstract = "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.",
keywords = "cryptorchidism, Leydig insulin-like protein, models, animal, spermatic cord torsion",
author = "Selami Sozubir and Theodore Barber and Yi Wang and Chul Ahn and Shaohua Zhang and Sunita Verma and Devin Lonergan and Lorenzo, {Armando J.} and Serge Nef and Baker, {Linda A.}",
year = "2010",
month = "6",
doi = "10.1016/j.juro.2010.02.2390",
language = "English (US)",
volume = "183",
pages = "2373--2379",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "6",

}

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 - cryptorchidism

KW - Leydig insulin-like protein

KW - models, animal

KW - spermatic cord torsion

UR - http://www.scopus.com/inward/record.url?scp=77951879259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951879259&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2010.02.2390

DO - 10.1016/j.juro.2010.02.2390

M3 - Article

C2 - 20400152

AN - SCOPUS:77951879259

VL - 183

SP - 2373

EP - 2379

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 6

ER -