The CAG repeat within the androgen receptor gene and its relationship to cryptorchidism

Abstract

Purpose:We examined the significance of the CAG repeat polymorphism in the pathogenesis of cryptorchidism. Materials and Methods: Genomic deoxyribonucleic acid (DNA) was extracted from blood samples from 42 cryptorchid boys and from 31 non-cryptorchid control subjects. In the cryptorchid group, 7 had bilateral cryptorchidism and 6 had patent processus vaginalis in the contralateral side. To determine the number of CAG repeats, the DNA was amplified by polymerase chain reaction and sequenced. Results: The mean CAG repeat length in the AR gene was 22.5 (range 16 to 28) in patients and 21.5 (range 17 to 26) in controls (non-significant). Patients with bilateral cryptorchidism had a mean length of 24.3 (range 21 to 26) and patients with unilateral cryptorchidism and patent processus vaginalis in the contra lateral side had a mean of 25.2 (range 21 to 28), which was statistically different from controls (p = 0.015 and p = 0.005 respectively). Conclusion: CAG repeat length of the AR gene does not seem to play a major role in patients with unilateral cryptorchidism. However, in patients with bilateral undescended testis, a less functional androgen receptor through a longer polyglutamine chain may have a role in its pathogenesis. In the same way, patients with unilateral cryptorchidism a contralateral patent processus vaginalis have longer CAG repeats that might be responsible for a slower testicular descent and incomplete closure of the processus vaginalis.

Could androgen receptor gene CAG tract polymorphism affect spermatogenesis in men with idiopathic infertility?

“…Moreover, the number of AR-CAG repeat stretch was statistically higher in comparison with those assessed in FM (Table 1). Our data are in agreement with most results published until now [47][48][49][50][51] except for those of a more recent study [18]. These conflicting evidence, though, can be explained by the following factors: 1) the choice of selection criteria for the patients enrolment, taken the complexity of the syndrome characterized by several clinical aspects such as idiopathic (mono or bilateral) cryptorchidism with or without comorbidity (inguinal hernia, micropenis, hypospadia etc.,) and secondary cryptorchidism (hypogonadotropic hypogonadism, Klinefelter S.) [25]; 2) the close partnership with other genes and/or hormones in testicular descent process [25]; 3) the complexity of androgen action (genomomic and/or nongenomic action) in different target tissues [19,51].…”

“…These conflicting evidence, though, can be explained by the following factors: 1) the choice of selection criteria for the patients enrolment, taken the complexity of the syndrome characterized by several clinical aspects such as idiopathic (mono or bilateral) cryptorchidism with or without comorbidity (inguinal hernia, micropenis, hypospadia etc.,) and secondary cryptorchidism (hypogonadotropic hypogonadism, Klinefelter S.) [25]; 2) the close partnership with other genes and/or hormones in testicular descent process [25]; 3) the complexity of androgen action (genomomic and/or nongenomic action) in different target tissues [19,51]. Conversely, the ethnic difference of number of AR-CAG repeats should not be retained as a significant cause for these contrasting data since all groups that have been studied so far, with the exception of study by Davis-Dao C et [18], have reported a longer AR-CAG repeat length in comparison with the fertile men independently of their ethnic origin [41,[47][48][49][50].…”

Factors controlling testis descent

“…These include premature adrenarche and acne in females, and an increased risk of metastatic disease in prostate cancer (34,35). Conversely, longer CAG repeats have been associated with idiopathic hypospadias, undescended testes and decreased sperm counts (36)(37)(38). The association with cryptorchidism is stronger when combined analysis of CAG and GGC repeat lengths is performed (39).…”

The Second-to-Fourth Digit Ratio in Cryptorchidism: A Case-Control Study

“…A high number of CAG repeats has been associated with cryptorchidism, especially bilateral cases, and the combination of CGA/GGC repeat length is strongly associated with cryptorchidism [18-22]. Silva-Ramos et al [20] reported that longer CAG repeats may be associated with slower testicular descent and incomplete closure of the processus vaginalis. However, there was no significant difference in CAG repeat length in unilateral cryptorchidism and in the patent processus vaginalis compared with controls [20].…”

“…Silva-Ramos et al [20] reported that longer CAG repeats may be associated with slower testicular descent and incomplete closure of the processus vaginalis. However, there was no significant difference in CAG repeat length in unilateral cryptorchidism and in the patent processus vaginalis compared with controls [20]. Sasagawa et al [23] did not find an association between CAG repeat length and cryptorchidism and suggested that the expansion of CAG repeats is unlikely to be a major cause of cryptorchidism in the Japanese population.…”