AZFa, AZFb, AZFc and gr/gr Y-chromosome microdeletions in azoospermic and severe oligozoospermic patients, analyzed from a neural network perspective.

AIM: Analysis of male infertility by molecular methods has increased since recognition of genetic risk factors. The AZFa, AZFb, AZFc, and gr/gr regions on the Y-chromosome can cause male infertility. The aim of this study was to determine the prevalence of Y-chromosome microdeletions in these regions in infertile Mexican patients. MATERIAL AND METHODS: We recruited 57 infertile patients with abnormal sperm count (26 azoospermic and 31 oligozoospermic) and 55 individuals with normal sperm count. Analysis of the regions of interest was performed by PCR. RESULTS: 15.8% of infertile patients presented Y-chromosome microdeletions, whereas no deletions were found in the control group. Deletions were observed in all the analyzed regions except in AZFa. Additionally, the neural network model revealed a mild genotype-phenotype correlation between deletion of the sY1191, sY1291 and sY254 markers with oligozoospermia, azoospermia and cryptozoospermia, respectively. CONCLUSIONS: Our data show that AZFb, AZFc, and gr/gr microdeletions are significantly associated with infertility in Mexican population. In addition, the neural network model revealed a discrete genotype-phenotype correlation between specific deletions and a particular abnormality. Our results reinforce the importance of the analysis of AZF regions as part of the clinical approach of infertile men.

OBJETIVO: La utilización de técnicas moleculares para estudiar la infertilidad masculina se ha incrementado desde el reconocimiento de factores genéticos. Las regiones AZFa, AZFb, AZFc, y gr/gr del cromosoma Y son causa de infertilidad masculina. El objetvo de este estudio fue determinar la prevalencia de microdeleciones en estas regiones en pacientes infértiles Mexicanos. MATERIAL Y MÉTODOS: Reclutamos 57 pacientes infértiles con cuentas espermáticas anormales (26 con azoospermia y 31 con oligozoospermia) y 55 individuos con cuentas espermáticas normales. El análisis de las regiones se realizó mediante PCR. RESULTADOS: 15.8% de los pacientes infértiles presentó microdeleciones, no se encontraron microdeleciones en el grupo control. Las microdeleciones fueron observadas en todas las regiones excepto en AZFa. Adicionalmente, el modelo de red neuronal reveló una leve correlación genotipo-fenotipo entre microdeleciones de los marcadores sY1191, Sy1291 y sY254 con oligozoospermia, azoospermia y criptozoospermia, respectivamente. CONCLUSIONES: Nuestros datos muestran que las microdeleciones en AZFb, AZFc, y gr/gr se asocian significativamente con infertilidad en la población Mexicana. Además, el modelo de red neuronal reveló una discreta correlación genotipo-genotipo entre microdeleciones específicas con una anormalidad en particular. Nuestros resultados refuerzan la importancia del análisis de las regiones AZF en el abordaje de la infertilidad masculina.

Hyperglycemia differentially affects proliferation, apoptosis, and BNIP3 and p53 mRNA expression of human umbilical cord Wharton's jelly cells from non-diabetic and diabetic pregnancies.

Diabetes in pregnancy constitutes an unfavorable environment for embryonic and fetal development, where the child has a higher risk of perinatal morbidity and mortality, with high incidence of congenital malformations and predisposition to long-term metabolic diseases that increase with a hypercaloric diet. To analyze whether hyperglycemia differentially affects proliferation, apoptosis, and mRNA expression in cells from children of normoglycemic pregnancies (NGPs) and diabetes mellitus pregnancies (DMPs), we used umbilical cord Wharton jelly cells as a research model. Proliferation assays were performed to analyze growth and determine the doubling time, and the rate of apoptosis was determined by flow cytometry-annexin-V assays. AMPK, BNIP3, HIF1α, and p53 mRNA gene expression was assessed by semi-quantitative RT-PCR. We found that hyperglycemia decreased proliferation in a statistically significant manner in NGP cells treated with 40 mM D-glucose and in DMP cells treated with 30 and 40 mM D-glucose. Apoptosis increased in hyperglycemic conditions in NGP and DMP cells. mRNA expression of BNIP3 and p53 was significantly increased in cells from DMPs but not in cells from NGPs. We found evidence that maternal irregular metabolic conditions, like diabetes with hyperglycemia in culture, affect biological properties of fetal cells. These observations could be a constituent of fetal programming.