The molecular basis of cryptorchidism
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The molecular basis of cryptorchidism. / Ivell, Richard; Hartung, Stefan.
In: MOL HUM REPROD, Vol. 9, No. 4, 01.04.2003, p. 175-81.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research
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TY - JOUR
T1 - The molecular basis of cryptorchidism
AU - Ivell, Richard
AU - Hartung, Stefan
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Cryptorchidism is the commonest malady to affect newborn male infants. Until recently, the molecular aetiology of this syndrome was unclear. Cryptorchidism may be part of a broader testicular dysgenesis syndrome, wherein a disturbance in steroid hormone metabolism, possibly through a perturbed hypothalamic-pituitary-gonadal axis could be involved. Disturbance may be genetic, or extrinsic through endocrine disruptors. Recently, the role of insulin-like factor-3 (INSL3; alternatively called relaxin-like factor) has been highlighted through the cryptorchid phenotype of mice where genes for either INSL3 or its receptor have been ablated. INSL3 is produced by Leydig cells of the fetal testis and acts upon the gubernacular ligament to retain the gonad in the inguinal region, from which it later passes into the scrotum. INSL3 expression in fetal testis is inhibited by maternal exposure to estrogens. Although to date no mutations have been found in the human INSL3 gene responsible for cryptorchidism, one causative mutation in the INSL3 receptor (LGR8 or GREAT) has been reported. Studies on developmental transcription factors, such as Hoxa-10 in mice, suggest that other specific molecular cascades could also lead to a cryptorchid phenotype. Considering its frequency in newborn children, and the severity of the untreated condition (infertility and often testicular cancer) these new findings should generate new information on possible causes and treatments.
AB - Cryptorchidism is the commonest malady to affect newborn male infants. Until recently, the molecular aetiology of this syndrome was unclear. Cryptorchidism may be part of a broader testicular dysgenesis syndrome, wherein a disturbance in steroid hormone metabolism, possibly through a perturbed hypothalamic-pituitary-gonadal axis could be involved. Disturbance may be genetic, or extrinsic through endocrine disruptors. Recently, the role of insulin-like factor-3 (INSL3; alternatively called relaxin-like factor) has been highlighted through the cryptorchid phenotype of mice where genes for either INSL3 or its receptor have been ablated. INSL3 is produced by Leydig cells of the fetal testis and acts upon the gubernacular ligament to retain the gonad in the inguinal region, from which it later passes into the scrotum. INSL3 expression in fetal testis is inhibited by maternal exposure to estrogens. Although to date no mutations have been found in the human INSL3 gene responsible for cryptorchidism, one causative mutation in the INSL3 receptor (LGR8 or GREAT) has been reported. Studies on developmental transcription factors, such as Hoxa-10 in mice, suggest that other specific molecular cascades could also lead to a cryptorchid phenotype. Considering its frequency in newborn children, and the severity of the untreated condition (infertility and often testicular cancer) these new findings should generate new information on possible causes and treatments.
KW - Androgens
KW - Animals
KW - Anti-Mullerian Hormone
KW - Calcitonin Gene-Related Peptide
KW - Cryptorchidism
KW - Estrogens
KW - Glycoproteins
KW - Growth Inhibitors
KW - Homeodomain Proteins
KW - Humans
KW - Insulin
KW - Male
KW - Mutation
KW - Proteins
KW - Testicular Hormones
KW - Testis
M3 - SCORING: Journal article
C2 - 12651898
VL - 9
SP - 175
EP - 181
JO - MOL HUM REPROD
JF - MOL HUM REPROD
SN - 1360-9947
IS - 4
ER -