The FSHR G-29A variant is not associated with the ovarian response to exogenous FSH stimulation.

A common genetic variant in the follicle stimulating hormone receptor gene (FSHR) 5'-untranslated region has been previously reported to influence FSHR gene expression. However, studies on the ovarian response to exogenous gonadotropin stimulation are limited. The aim of this study was to evaluate the association of variants at positions -29 of the FSHR gene with the ovarian response to exogenous FSH stimulation in Chinese women. The genotypes of the FSHR gene were assayed using the Sequenom MassARRAY system. Total RNA and protein was extracted from granulosa cells, and FSHR expression at the mRNA and protein levels was assessed using quantitative PCR and western blotting. Our data revealed that there was no association between the FSHR genotype at the -29 position and the outcome of controlled ovarian stimulation. The expression of FSHR, at both the mRNA and protein levels, was similar amongst the different FSHR genotypes assessed, but was significantly reduced in the low responders. These results indicate that the variants caused by mutations at position -29 are not associated with ovarian response, and the low ovarian response to gonadotropin stimulation may be caused by decreased FSHR expression.

Sequence variants in FSHR and CYP19A1 genes and the ovarian response to controlled ovarian stimulation.

OBJECTIVE: To examine whether sequence variants within the FSHR and CYP19A1 genes are related to the ovarian response to controlled ovarian stimulation (COS). DESIGN: Genetic association study using both single-gene and combined analyses of women with sequence variants undergoing in vitro fertilization treatment. SETTING: Academic research institute hospital. PATIENT(S): Seven hundred and five women undergoing ovarian stimulation with recombinant follicle-stimulating hormone (FSH). INTERVENTION(S): Peripheral blood extraction, DNA purification, and FSHR c.919G>A (rs6165, p.Thr307Ala) and CYP19A1 c.*19C>T (rs10046) sequence variants analyses. MAIN OUTCOME MEASURE(S): Single-gene statistical analysis and combined statistical analysis with the SPSS17.0 software; FSHR c.919G>A and CYP19A1 c.*19C>T sequence variant genotypes and clinical parameters related to the COS response as oocyte retrieval and hormone levels, doses of exogenous FSH. RESULT(S): Women with genotype Ala/Ala at FSHR position 307 had higher basal levels of FSH and were more likely to have a low ovarian response compared with other genotypes. Women with genotype TT at CYP19A1 yielded fewer oocytes after ovarian stimulation. The combined analysis of these two sequence variants revealed that these two single-nucleotide variants have a synergistic effect in conferring the risk of a low ovarian response. CONCLUSION(S): Our results support an association of sequence variants in the genes that participate in estrogen synthesis, notably the FSHR and CYP19A1 genes, with the outcome of COS.

Roles of mechanical force and CXCR1/CXCR2 in shear-stress-induced endothelial cell migration.

We previously demonstrated that CXCR1 and CXCR2 are novel mechanosensors mediating laminar shear-stress-induced endothelial cell (EC) migration (Zeng et al. in Cytokine 53:42-51, 2011). In the present study, an analytical model was proposed to further analyze the underlying mechanisms, assuming the mechanical force (MF) and mechanosensor-mediated biochemical reactions induce cell migration together. Shear stress can regulate both mechanosensor-mediated migration in the flow direction (Ms-M(FD)) and mechanosensor-mediated migration toward a wound (Ms-M(W)). Next, the migration distance, the roles of MF-induced cell migration (MF-M), and the mobilization mechanisms of mechanosensors were analyzed. The results demonstrated that MF-M plays an important role in 15.27 dyn/cm(2) shear-stress-induced EC migration but is far weaker than Ms-M(W) at 5.56 dyn/cm(2). Our findings also indicated that CXCR2 played a primary role, in synergy with CXCR1. The Ms-M(FD) was primarily mediated by the synergistic effect of CXCR1 and CXCR2. In Ms-M(W), when shear stress was beyond a certain threshold, the synergistic effect of CXCR1 and CXCR2 was enhanced, and the effect of CXCR1 was inhibited. Therefore, the retarding of EC migration and wound closure capacity under low shear flow was related to the low magnitude of shear stress, which may contribute to atherogenesis and many other vascular diseases.