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Cryptorchidism in mice mutant for Insl3

Abstract

Impaired testicular descent (cryptorchidism) is one of the most frequent congenital abnormalities in humans, involving 2% of male births1. Cryptorchidism can result in infertility and increases risk for development of germ-cell tumours. Testicular descent from abdomen to scrotum occurs in two distinct phases: the trans-abdominal phase and the inguino-scrotal phase1,2,3. Currently, little is known about the factors that regulate the trans-abdominal phase of testicular descent. Leydig insulin-like hormone (Insl3) is a member of the insulin hormone superfamily4 expressed in the developing testis5. We show here that mice mutant for Insl3 are viable, but exhibit bilateral cryptorchidism due to developmental abnormalities of the gubernaculum, resulting in abnormal spermatogenesis and infertility. Female homozygotes have impaired fertility associated with deregulation of the oestrus cycle. These findings reveal roles for Insl3 in the development of the urogenital tract and in female fertility. Insl3 may act as a hormone to regulate the growth and differentiation of the gubernaculum, thereby mediating intra-abdominal testicular descent.

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Figure 1: Targeted disruption of Insl3.
Figure 3: Histology of wild-type and mutant testis.
Figure 2: Cryptorchidism in Insl3-/- male mice.
Figure 5: SEM of the urogenital anatomy of neonates.
Figure 4: Anatomy of male genitalia.
Figure 6: Histological sections of gubernacula at 16.

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Acknowledgements

We thank J. Wilson, J. Graff, W. Neaves and D. Russel for discussion and comments on the manuscript; T. Shipman and S. Karzhai for technical support; G. Lawton for assistance with SEM pictures; and D. Hess for testosterone measurements. This work was supported in part by a grant from the Swiss National Science Foundation (S.N., 81GE-18118) and by Excellence in Education Grant (L.F.P. and S.N.).

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Correspondence to Luis F. Parada.

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Nef, S., Parada, L. Cryptorchidism in mice mutant for Insl3. Nat Genet 22, 295–299 (1999). https://doi.org/10.1038/10364

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