A novel mutation of the insulin-like 3 gene in patients with cryptorchidism

Canto, Patricia; Escudero, Irineo; Söderlund, Daniela; Nishimura, Elisa; Carranza-Lira, Sebastián; Gutiérrez, Jesús N.; Nava, A Gutiérrez; Méndez, Juan Pablo

doi:10.1007/s100380300012

Cited by 58 publications

(32 citation statements)

References 25 publications

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“…The involvement of this gene in human cases of cryptorchidism has also been demonstrated. Indeed, heterozygous mutations have been reported in human cases of unilateral and bilateral cryptorchidism (Marin et al, 2001;Canto et al, 2003;Ferlin et al, 2003). Finally, also heterozygous mutations in RXFP2 (alias LGR8 or GREAT) were identified in human cryptorchid patients (Gorlov et al, 2002;Ferlin et al, 2003) and the involvement of this gene in cryptorchidism was confirmed by analyzing mutant mice (Gorlov et al, 2002).…”

mentioning

confidence: 76%

Clinical, cytogenetic and molecular evaluation in a dog with bilateral cryptorchidism and hypospadias

Cassata¹,

Iannuzzi

Parma³

et al. 2008

Cytogenet Genome Res

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The aim of this study was to estimate prognostic factors in a Dalmatian dog with bilateral cryptorchidism and hypospadias. Cytogenetic and molecular analyses revealed a normal karyotype (2n = 78,XY) and the presence of SRY, INSL3 and RXFP2 genes with a normal DNA sequence for SRY and RXFP2, while the INSL3 sequence differed slightly from the normal one due to a heterozygous nucleotide change involving amino acid 22 of the INSL3 dog precursor protein. Levels of plasmatic testosterone were only 0.01 ng/ml, while FSH and LH serum levels were not detectable. After the human chorionic gonadotropin (hCG) test, the serum testosterone level was 0.01 ng/ml. Therefore, the phenotypic aetiology of this subject can not be well-defined because cryptorchidism and hypospadias were frequent clinical features with high genetic heterogeneity.

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mentioning

confidence: 76%

Clinical, cytogenetic and molecular evaluation in a dog with bilateral cryptorchidism and hypospadias

Cassata¹,

Iannuzzi

Parma³

et al. 2008

Cytogenet Genome Res

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“…However, INSL3 and LGR8/GREAT mutations are known to cause various types of CO [5,6,7,8], and fertility appears to be preserved in patients with INSL3 and LGR8/GREAT mutations by performing orchidopexy at an early age [25]. Thus, molecular studies of INSL3 and LGR8/GREAT would be worth continuing.…”

Section: Resultsmentioning

confidence: 99%

“…Although it might be possible that a mutation(s) remained undetected by the DHPLC analysis or existed in an unexamined region such as the promoter and the intron sequences, the results imply that mutations of INSL3 and LGR8 / GREAT remain rare in patients with CO. Indeed, only a few mutations have been found in INSL3 , and only a single mutation of a probable common founder origin has been identified in LGR8 / GREAT [2,5,6,7,8]. The rarity would at least in part be due to a direct or indirect association between CO and defective spermatogenesis [1], because this would affect transmission of a mutation through males.…”

Section: Discussionmentioning

confidence: 99%

“…Homozygous Insl3 or Lgr8 / Great deficiency leads to bilateral intra-abdominal CO in mice because of impaired gubernacular development [3, 4] and heterozygous INSL3 or LGR8/GREAT mutations have been identified in human males with CO [5,6,7,8]. However, the mutations remain infrequent, and there has been no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT .…”

Section: Introductionmentioning

confidence: 99%

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Mutation and Polymorphism Analyses of INSL3 and LGR8/GREAT in 62 Japanese Patients with Cryptorchidism

Yamazawa¹,

Wada²,

Sasagawa

et al. 2006

Horm Res Paediatr

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Background/Aims: Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO. Methods: Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns. Results: No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p = 0.0024, odds ratio = 5.3, 95% confidence interval = 1.7–17). Conclusion: The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.

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“…Testicular oxidative stress appears to be a common 231 feature in much of what underlies male infertility (Canto et al, 2003), which suggests that there may be benefits to developing better and cheaper antioxidant therapies for relevant cases of hypospermatogenesis. Therefore, the present study was designed to investigate the antioxidant activity of the methanolic extract of Moringa oleifera leaves in an experimentally-induced cryptorchidism in rats.…”

Section: Introductionmentioning

confidence: 99%

Effects of methanolic extract of Moringa Oleifera leave on semen and biochemical parameters in cryptorchid rats

Afolabi¹,

Aderoju²,

Alagbonsi³

2013

Afr. J. Trad. Compl. Alt. Med.

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While anti-oxidant effects of Moringa oleifera in much oxidative stress related diseases have been well reported, cryptorchidism on the other hand has been shown to cause oxidative stress. However, study is scanty on the likely role of Moringa oleifera in reducing cryptorchidism-induced oxidative stress in rats has not been studied. The present study looked into the effects of methanolic extract of Moringa oleifera leaves (MEMO) on semen and biochemical parameters in cryptorchid rats. Twenty male albino rats (200-250g) were randomly divided into 4 groups (n=5 each). Groups A and B were sham-operated and treated with corn-oil and 200mg/kg of MEMO respectively, while groups C and D were rendered cryptorchid and also treated with corn-oil and 200mg/kg of MEMO respectively. Cryptorchid rats had lower testicular weight, sperm count, germ cell count, testicular superoxide dismutase (SOD) concentration, testicular total protein and higher testicular malondialdehyde (MDA) concentration compared to sham-operated rats. MEMO had no significant effect on testicular weight and MDA concentration, while it significantly increased sperm count, germ cell count, testicular SOD and total protein in the cryptorchid rats. The present study suggests that MEMO ameliorates cryptorchidism associated germ cell loss and oxidative stress.

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A novel mutation of the insulin-like 3 gene in patients with cryptorchidism

Cited by 58 publications

References 25 publications

Clinical, cytogenetic and molecular evaluation in a dog with bilateral cryptorchidism and hypospadias

Clinical, cytogenetic and molecular evaluation in a dog with bilateral cryptorchidism and hypospadias

Mutation and Polymorphism Analyses of <i>INSL3</i> and <i>LGR8</i>/<i>GREAT</i> in 62 Japanese Patients with Cryptorchidism

Effects of methanolic extract of <i>Moringa Oleifera</i> leave on semen and biochemical parameters in cryptorchid rats

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