Changes in receptivity epithelial cell markers of endometrium after ovarian stimulation treatments: its role during implantation window.

BACKGROUND: To compare the expression of receptivity markers in epithelial and stromal cells in the endometrium of ovulatory women and infertile with hypothalamic pituitary dysfunction (HPD), untreated or treated with clomiphene citrate (CC), or with recombinant follicle stimulating hormone (rFSH). METHODS: Twelve control ovulatory and 32 anovulatory women, 22 of whom received ovulation induction with CC (n = 12) or rFSH (n = 10). Endometrial biopsies were obtained during the mid-secretory phase. Hormonal secretion was measured by chemiluminescence immunoassay, endometrial dating and cellular expression and distribution of receptivity proteins were evaluated by quantitative immunohistochemistry. RESULTS: CC or rFSH treatments, modified the expression of epithelial receptivity markers, such as Glycodelin A, beta-catenin, CD166/ALCAM and IGF-1R, but not in stromal markers. Also, a change in their cell distribution was observed. CONCLUSIONS: Treatment of infertile women with HPD modified the expression and distribution of receptivity markers in the mid-secretory phase of the endometrium in epithelial but not stromal cells, which can help to explain changes in the receptivity of the endometrium during treatments and suggest an important role of these cells in the receptivity window.

The FTO gene is associated with adulthood obesity in the Mexican population.

Common polymorphisms in the fat mass and obesity-associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican-Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single-nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B-cell function (HOMA-B), and with higher homeostasis model assessment of insulin sensitivity (HOMA-S) only in nonobese individuals (P (dom) = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican-Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.

Adhesion molecules changes at 20 gestation weeks in pregnancies complicated by preeclampsia.

OBJECTIVES: To examine soluble E-selectin, L-selectin, P-selectin, ICAM-1, and VCAM-1 levels in normotensive and preeclamptic pregnancies. To determine cut-offs useful for preeclampsia early detection. STUDY DESIGN: A cohort of nulliparous women was recruited at family medicine clinics in Mexico City. Preeclampsia developed in 75 patients; 125 normotensive controls were matched. Adhesion molecules were assessed in serum obtained at 20 gestation weeks and in third trimester pregnancies. Predictive values and odds ratios for preeclampsia development were calculated with the 20 gestation week results. Threshold values were selected based on ROC curves values. RESULTS: In women with subsequent preeclampsia, sL-selectin and sVCAM-1 concentrations were significantly lower, whereas sE-selectin, sP-selectin and sICAM-1 levels were significantly higher, compared with controls at mid-pregnancy (p<0.05). The odds ratio for low sL-selectin was 25.6 (95% CI, 8.9-73.5; cut-off, 1414 ng/ml). The sensitivity, specificity, and positive and negative predictive values of low sL-selectin for preeclampsia development were 84, 90, 39, and 98%, respectively, whereas its sensitivity, specificity, and positive and negative predictive values for severe preeclampsia development (cut-off, 1210 ng/ml) were 100, 98, 60, and 100%, respectively. CONCLUSIONS: Early enhanced activation of endothelial cells, platelets and leukocytes seem to be present in preeclamptic patients, especially in those that develop severe preeclampsia. Low sL-selectin levels at 20 gestation weeks may be an indicator of preeclampsia development.

Methionine inhibits cellular growth dependent on the p53 status of cells.

BACKGROUND: Methionine, an essential amino acid, is important for normal growth and development, as it is required for both protein and polyamine synthesis as well as in methylation reactions. It has been reported that high concentrations of methionine inhibit cellular growth and gene expression in the human breast tumor-derived MCF-7 cells. These effects are thought to be mediated by the modulation of p53. However, the generalizability of this observation and the precise role of p53 in methionine-induced growth suppression needs to be determined. METHODS: To determine if the inhibition of cell growth by methionine applies to other cell lines and to characterize further the role of p53 in methionine-induced growth suppression, we have assessed the effects of methionine on cellular growth and proliferation and p53 expression in cells expressing native p53, eg, breast cancer MCF-7 cells and prostate cancer LNCaP cells, and also in cells expressing a mutated (point) form of p53, eg, prostate cancer DU-145 cells. These cell lines were treated with varying concentrations of L-methionine. The effects of L-methionine on cell growth were assayed by using cell viability assays and immunostaining for Ki-67, a cell proliferation marker. The effects of methionine on p53 expression were assessed by using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot analysis. The role of p53 in L-methionine-mediated growth suppression was evaluated using short-interference RNA for p53 (siRNA-p53), immunoprecipitation, and direct DNA sequencing. RESULTS: We demonstrated that methionine at a concentration of 1 to 5 mg/mL inhibited the growth of both MCF-7 and LNCaP cells. In association with the inhibition of growth, methionine also inhibited native p53 expression at the mRNA and protein levels, respectively. Furthermore, transfection with siRNA-p53, to knock down p53 expression, increased cell growth and proliferation of the LNCaP cells even when they were exposed to methionine. In contrast, the same treatment did not diminish growth or proliferation of the DU-145 cells. Also, the expression of mutated p53 at the mRNA or protein levels was not altered. CONCLUSION: Our results extend a prior observation to other cell lines and demonstrate that high concentrations of methionine suppress the expression of native but not mutated p53. These inhibitory effects on cellular growth are, in part, due to inhibition of cellular proliferation probably via a p53-dependent pathway.