RESUMO
Cryptorchidism is a frequent genitourinary malformation considered as an important risk factor for infertility and testicular malignancy. The aetiology of cryptorchidism is multifactorial in which certain SNPs, capable of inhibiting the development of the gubernaculum, are implicated. We analysed 16 SNPs by allelic discrimination and automated sequencing in 85 patients and 99 healthy people, with the objective to identify the association between these variants and isolated cryptorchidism. In two different patients with unilateral cryptorchidism, we found the variants rs121912556 and p.R105R of INSL3 gene in a heterozygous form associated with cryptorchidism, so we could considered them as risk factors for cryptorchidism. On the other hand, SNPs rs10421916 of INSL3 gene, as well as the variants rs1555633 and rs7325513 in the RXFP2 gene, and rs3779456 variant of the HOXA10 gene were statistically significant, when the patients and controls were compared and could be considered as protective factors since are predominantly present in controls. The genotype-phenotype correlation did not show statistical significance. With these results, we could conclude that these polymorphisms can be considered as important variants in our population and would contribute in the future knowledge of the aetiology and physiopathology of cryptorchidism.
Assuntos
Criptorquidismo/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Criança , Pré-Escolar , Estudos de Associação Genética , Haplótipos , Proteínas Homeobox A10 , Proteínas de Homeodomínio/genética , Humanos , Lactente , Insulina/sangue , Insulina/genética , Desequilíbrio de Ligação , Masculino , México , Proteínas/genética , Receptores Acoplados a Proteínas G/genéticaRESUMO
Pyrimethamine (PYR) is a drug used in the treatment of newborn with congenital Toxoplasmosis. Even when PYR is highly specific against parasites, it may provoke neutropenia in the patients apart from other affectations, conditions that usually justify its suspension. Moreover, medication against congenital toxoplasmosis coincides with the proliferation stage of Sertoli and germ cells. Although, there are several reports on the effect of this drug on mature testes, records of its effects on the testes of young individuals yet in the process of growth are still lacking. This work was aimed to study the effects of in vivo administration of PYR in the first 21 days of life of male rat pups by evaluating their testicular alterations and its long-term sequels on fertility. Through the determination of the levels of seminiferous epithelium maturity, apoptotic index and cell proliferation index at 7, 14, 35 and 90 days post-natal using immunocytochemical studies. The fertility of the treated rats was evaluated at 90 days. PYR-treated animals were found to undergo some kind of delays in seminiferous epithelium maturity, decreased cell proliferation index and an increase in apoptosis when compared with the control (p < 0.05). Epididymal sperm counts were also affected (p < 0.05). The application of folic acid (FA) in newborns treated with PYR decreased the severity of the problem (p < 0.05). This study provides strong evidence that the effect of PYR on testicular development is specific. It reinforces the importance of FA application in neonates treated with PYR to prevent the effect of the later on spermatogenesis.