RESUMEN
To evaluate the effects of follicle-stimulating hormone (FSH) treatment on cytokine gene expression in cultured Sertoli cells from men with nonobstructive azoospermia, a total of 15 azoospermic men diagnosed as obstructive azoospermia (OA) (n = 5) and nonobstructive azoospermia (NOA) (n = 10) were included in the study. NOA patients were split into two further subgroups: nFSH and hFSH serum FSH levels. Expression of cytokine gene panel (88 genes), FSHR and ABP was evaluated by real-time PCR array analysis. FSHR protein level was measured by the Western blot. In primary cultures of Sertoli cells, seven genes were found to be increased and 13 were decreased in NOA group, when compared to OA (p < .05). When rFSH was introduced into the culture media, expression of 12 genes in the NOA group restored a comparable level to those of the control OA group. Sertoli cells in all groups responded rFSH administration with increased expression of ABP. Our results suggest that FSH treatment may have positive effects on Sertoli cells of nonobstructive azoospermic patients via changing the expression levels of certain genes and restoring their levels in normal Sertoli cell population. Some cytokine levels can be considered as a potential candidate for detecting NOA patients. ABP is a good marker for cell viability and functionality in primary Sertoli cell culture.
Asunto(s)
Azoospermia/metabolismo , Citocinas/metabolismo , Hormona Folículo Estimulante Humana/farmacología , Células de Sertoli/efectos de los fármacos , Espermatogénesis , Proteína de Unión a Andrógenos/análisis , Azoospermia/sangre , Supervivencia Celular , Hormona Folículo Estimulante Humana/sangre , Humanos , Masculino , Cultivo Primario de Células , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de HFE/análisis , Proteínas Recombinantes/farmacología , Células de Sertoli/metabolismoRESUMEN
Infertility affects 1 in 6 couples and approximately 1 in 25 men. Male factor infertility is a major cause of spermatogenic anomalies, the causes of which are largely unknown. Impaired repro-ductive functions in men might result from physiological, genetic, and/or environmental factors such as xenobiotics. The multi-drug re-sistance1 (MDR1) gene encodes a P-glycoprotein which has a role in the active transport of various substrates providing protection of somatic cells from potentially toxic substances, including xenobi-otics. MDR1 is highly expressed at the luminal surface of capillary endothelial cells, and is expressed in Leydig cells, testicular mac-rophages, and Sertoli cells. We performed genotype and haplotype analyses of MDR1 in 192 infertile and 102 fertile Turkish men for the genetic markers C1236T and C3435T, using polymerase chain reaction-restriction fragment length polymorphism analysis. In the overall population, correlations were analyzed in all genotype mod-els. We found that the C3435T polymorphism TT vs CT genotypes showed statistically significant differences in their association with infertility (P = 0.045), and that the CT genotype was associated with high sperm DNA damage (P = 0.02), suggesting that the CT genotype might be a susceptibility factor for infertility. Additionally, the T-T haplotype was significantly more frequent in the control group (13.2 vs 6.5%; odds ratio = 0.459, 95%CI = 0.259-0.814, P = 0.006). This study showed that MDR1 might have a role in male infertility. Fur-ther research in large cohorts with different populations is required to clarify the role of MDR in male fertility.