[Correlation between offspring congenital heart disease and MTHFR 677C/T polymorphism and general status of pregnant women].

OBJECTIVE: To understand the relationship between MTHFR 677C/T polymorphism and general status of pregnant women and offspring congenital heart disease (CHD). METHODS: A case-control study was conducted among the biological mothers of 100 infants with CHD and 100 healthy controls to collect the information about their demographic characteristics, general status during pregnancy and awareness of eugenics. Their MTHFR 677C/T polymorphism and serum homocysteine (HCY), folic acid, vitamin B12 levels were detected. RESULTS: The differences in MTHFR genotype and allele frequency between the two groups were not statistical significant (χ² =1.08, P=0.582; χ² =0.53, P=0.468) , but the difference in serum HCY between two groups were statistical significant (t=-8.14, P=0.000). Univariate analysis showed that 14 factors had statistical significances (P<0.05). Multivariate logistic regression analysis indicated that mother's educational level (OR=3.386, 95% CI: 1.279-8.961), annual household income (OR=8.699, 95% CI: 2.177-34.765), chronic disease prevalence (OR=0.343, 95% CI: 0.134-0.881) , awareness of eugenics (OR=0.906, 95% CI: 0.836-0.981), serum HCY level (OR=1.734, 95% CI: 1.458-1.986) and abnormal reproductive history (OR=3.710, 95% CI: 1.217-11.308) were correlated with offspring CHD. CONCLUSION: There was no correlation between MTHFR 677C/T polymorphism of pregnant women and offspring CHD, but low educational level, low annual household income, abnormal reproductive history, low awareness of eugenics and high serum HCY levels of pregnant women might increase the risk of offspring CHD.

Heat shock protein 90 has roles in intracellular calcium homeostasis, protein tyrosine phosphorylation regulation, and progesterone-responsive sperm function in human sperm.

Heat shock protein 90 plays critical roles in client protein maturation, signal transduction, protein folding and degradation, and morphological evolution; however, its function in human sperm is not fully understood. Therefore, our objective in this study was to elucidate the mechanism by which heat shock protein 90 exerts its effects on human sperm function. By performing indirect immunofluorescence staining, we found that heat shock protein 90 was localized primarily in the neck, midpiece, and tail regions of human sperm, and that its expression increased with increasing incubation time under capacitation conditions. Geldanamycin, a specific inhibitor of heat shock protein 90, was shown to inhibit this increase in heat shock protein 90 expression in western blotting analyses. Using a multifunctional microplate reader to examine Fluo-3 AM-loaded sperm, we observed for the first time that inhibition of heat shock protein 90 by using geldanamycin significantly decreased intracellular calcium concentrations during capacitation. Moreover, western blot analysis showed that geldanamycin enhanced tyrosine phosphorylation of several proteins, including heat shock protein 90, in a dose-dependent manner. The effects of geldanamycin on human sperm function in the absence or presence of progesterone was evaluated by performing chlortetracycline staining and by using a computer-assisted sperm analyzer. We found that geldanamycin alone did not affect sperm capacitation, hyperactivation, and motility, but did so in the presence of progesterone. Taken together, these data suggest that heat shock protein 90, which increases in expression in human sperm during capacitation, has roles in intracellular calcium homeostasis, protein tyrosine phosphorylation regulation, and progesterone-stimulated sperm function. In this study, we provide new insights into the roles of heat shock protein 90 in sperm function.