Transabdominal testicular descent is disrupted in mice with deletion of insulinlike factor 3 receptor
Section snippets
Materials and methods
The mutant crsp mice used in this study were produced by intercrossing of heterozygous males and homozygous females. Macroscopically, crsp/+ heterozygous males have the same degree of descent as that in wild-type males; therefore, we have used heterozygous littermates as the wild-type controls.
In this study, 4 crsp/crsp homozygous and 7 heterozygous males at birth (D 0), 5 crsp/crsp homozygous and 5 heterozygous males at day 10 after birth (D 10), and 6 crsp/crsp homozygous males and 5 crsp/crsp
Results
Morphologic analysis of the crsp mutant mice showed inhibition of testicular descent. Mutant testes were located in a high intraabdominal position in all 3 analyzed age groups (Table 1).
Discussion
The results of this study show that the crsp mutation causes an anomaly of transabdominal testicular descent. The homozygote mutant mice had testes high on the posterior abdominal wall adjacent to the kidneys. Molecular genetic analysis of the crsp mutation showed that it caused a deletion of the Great gene encoding a novel G protein-coupled receptor.10 Great is highly expressed in the gubernaculum, testis, brain, and, to a lesser degree, in some other organs. Genetic targeting of the Great
References (21)
A biphasic model for the hormonal control of testicular descent
Lancet
(1985)- et al.
Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional redundancy and regulatory interactions
Dev Biol
(2000) - et al.
Mullerian-inhibiting substance function during mammalian sexual development
Cell
(1994) - et al.
INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent
J Biol Chem
(2002) - et al.
A novel Leydig cell cDNA-derived protein is a relaxin-like factor
J Biol Chem
(1995) - et al.
Leydig insulin-like hormone, gubernacular development and testicular descent
J Urol
(2001) - et al.
The undescended testis. Theory and management
Urol Clin North Am
(1995) - et al.
Hormonal control of gubernaculum development during testis descentGubernaculum outgrowth in vitro requires both insulin-like factor and androgen
Endocrinology
(2000) - et al.
Relaxin-like factor (RLF) serum concentrations and gubernaculum RLF receptor display in relation to pre-and neonatal development of rats
Reproduction
(2001) - et al.
Cryptorchidism in mice mutant for Insl3
Nat Genet
(1999)
Cited by (47)
Developmental genetics of the male reproductive system
2023, Human Reproductive and Prenatal GeneticsDevelopment of a putative adverse outcome pathway network for male rat reproductive tract abnormalities with specific considerations for the androgen sensitive window of development
2021, Current Research in ToxicologyCitation Excerpt :The first phase (transabdominal phase) beings around GD15.5 in rodents (Hutson et al., 1997, 2013, 2016; Klonisch et al., 2004) and is characterized by regression of the cranial suspensory ligament (CSL) and swelling of the gubernaculum to position the testes at the bottom of the abdomen. In this phase, CSL regression is initiated by testosterone (Amann and Veeramachanemi, 2007; Van der Schoot and Emmen, 1996), and the swelling reaction in the gubernaculum is stimulated primarily by insulin-like hormone 3 (INSL3) with some studies implicating secondary augmentation by androgens (Adham et al., 2002; Bogatcheva et al., 2003; Gorlov et al., 2002; Nef et al. 1999; Overbeek et al. 2001; Tomiyama et al., 2003; Zimmerman et al., 1999). The second phase of testicular descent (inguinoscrotal process) is largely controlled by androgens and occurs at approximately postnatal week 3 and involves movement of the testes from the bottom of the abdomen to the base of the scrotum (Klonisch et al 2004, Zimmerman et al., 1999).
Nonneoplastic Diseases of the Testis
2020, Urologic Surgical PathologyTargeting the relaxin/insulin-like family peptide receptor 1 and 2 with small molecule compounds
2019, Molecular and Cellular EndocrinologyCitation Excerpt :If left untreated, cryptorchidism causes a failure of spermatogenesis and germ cell apoptosis resulting in infertility as well as an increased risk of testicular cancer in adulthood (Barthold and Gonzalez, 2003). Analysis using transgenic mouse models renders two main conclusions: 1) INSL3 controls the outgrowth and differentiation of gubernacular ligaments, and the formation of processus vaginalis (scrotal sac) during prenatal development, and 2) INSL3 peptide is a paracrine anti-apoptotic factor for male and female germ cells in adult gonads (Adham and Agoulnik, 2004; Bogatcheva and Agoulnik, 2005; Bogatcheva et al., 2003; Feng et al., 2007; Gorlov et al., 2002; Huang et al., 2012; Kaftanovskaya et al., 2011; Overbeek et al., 2001; Tomiyama et al., 2003). Treatment with INSL3 initiates meiotic progression of arrested oocytes in preovulatory follicles in vitro and in vivo, and suppresses gonadotrophin-releasing hormone (GnRH) antagonist-induced male germ cell apoptosis in vivo, indicating importance of the INSL3 paracrine system in mediating gonadotropin actions in adult gonads (Kawamura et al., 2004).
Developmental genetics of the male reproductive system
2018, Human Reproductive and Prenatal GeneticsHuman Testicular Insulin-Like Factor 3 and Endocrine Disrupters
2014, Vitamins and Hormones