Disease relevance of Cryptorchidism

• 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 [1].
• But in two lines with the highest levels of MIS expression, some males showed feminization of the external genitalia, impairment of Wolffian duct development, and undescended testes [2].
• Here we describe the molecular detection of a cytogenetically invisible 1-megabase deletion in an individual with aniridia, cryptorchidism, and hypospadias but no Wilms tumor (WT) [3].
• CONCLUSION: Germline WT1 mutations in patients with WT are associated with genitourinary anomalies, especially cryptorchidism and/or hypospadias [4].
• Spermatic and peripheral plasma concentrations of testosterone (T) and androstenedione (A) have been measured in prepubertal boys affected by inguinal hernia (group I; n = 7) and unilateral undescended testis (group II; n = 18) [5].

Psychiatry related information on Cryptorchidism

• We report on two brothers and one maternal cousin with severe mental retardation, microcephaly, short stature, cryptorchidism, and spastic diplegia [6].

High impact information on Cryptorchidism

• Cryptorchidism in mice mutant for Insl3 [1].
• CONCLUSIONS: Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies [7].
• We conducted a randomized, double-blind study comparing intranasal gonadotropin-releasing hormone (1.2 mg per day for 28 days) with parenteral human chorionic gonadotropin (3300 IU per week for four weeks) in the treatment of cryptorchidism in 33 boys one to five years old (29 with unilateral and 4 with bilateral cryptorchidism) [8].
• Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives [9].
• Recently, we described a mouse transgene insertional mutation, crsp, causing high intraabdominal cryptorchidism in homozygous males [10].

Chemical compound and disease context of Cryptorchidism

• Seven of 36 patients with cryptorchidism had a positive family history of a similar disorder; testosterone levels were similar in patients with and without a family history [11].
• Serum androgen bioactivity was studied in 23 boys (13.9--16.8 yr old) with constitutional delay of puberty and in 9 prepubertal boys with cryptorchidism (1.0--6.4 yr old) [12].
• A molecular basis for estrogen-induced cryptorchidism [13].
• Controls excluded individuals with cryptorchidism, micropenis, known endocrine defects, or receiving steroid supplementation [14].
• Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of 17 prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair [15].

Biological context of Cryptorchidism

• Association of cryptorchidism with a specific haplotype of the estrogen receptor alpha gene: implication for the susceptibility to estrogenic environmental endocrine disruptors [16].
• Adenoviral-mediated HGF expression inhibits germ cell apoptosis in rats with cryptorchidism [17].
• The results do not support the hypothesis that cryptorchidism may be caused by high concentrations of oestradiol in the maternal blood during the first phase of testicular descent, but suggest that the possible association of cryptorchidism with low maternal testosterone during early gestation should be further investigated [18].
• In the present study, we have sequenced the promoter region and both exons of the RLF gene in a cohort of 30 boys, seven of whom presented with a possible familial form of cryptorchidism and 23 with sporadic cryptorchidism [19].
• This phenotype suggests that INSL3 may have a role in the development of human cryptorchidism [20].

Anatomical context of Cryptorchidism

• Here we show that male mice homozygous for a targeted deletion of the Insl3 locus exhibit bilateral cryptorchidism with free moving testes and genital ducts [21].
• Testosterone levels did not correlate with either the anatomical location of the testis in patients with unilateral cryptorchidism or with the site of the urethra in boys with hypospadias [11].
• Seminiferous tubules from cryptorchid testes remain responsive to FSH stimulation (500 ng/ml) up to 12 days of cryptorchidism [22].
• In an earlier study, estrogen production was much lower in Leydig cells from the abdominal than from the scrotal testis in naturally occurring unilateral cryptorchidism in the boar [23].
• The authors used stored serum samples to examine the relation between maternal DDE levels during pregnancy and adjusted odds of cryptorchidism (n = 219), hypospadias (n = 199), and polythelia (extra nipples) (n = 167) among male offspring, using a nested case-control design with one control group (n = 552) [24].

Gene context of Cryptorchidism

• Targeted disruption of the Insl3 gene causes bilateral cryptorchidism [21].
• The frequency of INSL3/RLF gene mutations as a cause of cryptorchidism is low, because only 2 of 145 (1.4%) formerly cryptorchid patients were found to have mutations [25].
• The present results indicate that cryptorchidism induces apoptotic dell death in germ cells, and that testosterone reduction and the Fas system may not be significantly involved in the apoptosis of male germ cells [26].
• Mutations of Insl3 or Great cause cryptorchidism (undescended testes) in mice [27].
• After cryptorchidism or busulfan treatment, mEP17 levels were either greatly diminished or not detected [28].

Analytical, diagnostic and therapeutic context of Cryptorchidism

• The clinical features included cleft lip and palate, preauricular pits, low set malpositioned auricles, antimongoloid slant of the eyes, microcephaly, micrognathia, congenital heart disease, hypertrophic pyloric stenosis, cryptorchidism, and abnormal dermatoglyphics [29].
• The recent discovery of time-specific antiandrogens (flutamide) to induce undescent of the testes has provided us the ability to study androgen therapy for cryptorchidism in the first specific antiandrogen animal model for testicular descent [30].
• RESULTS: Sperm density and total count, and basal and gonadotropin-releasing hormone stimulated follicle-stimulating hormone (FSH) levels were different in the cryptorchidism and control groups [31].
• Possible involvement of inhibin in altered follicle-stimulating hormone (FSH) secretion during dissociated luteinizing hormone (LH) and FSH release: unilateral castration and experimental cryptorchidism [32].
• Levels of luteinizing hormone, follicle-stimulating hormone, testosterone and dihydrotestosterone in the circulation of sexually maturing intact male rats and after orchidectomy and experimental bilateral cryptorchidism [33].

References