Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Objectives To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP). Materials and Methods This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13). Results According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both). Conclusions Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause. .

Association study of the oestrogen signalling pathway genes in relation to age at natural menopause.

Genetic factors play a significant role in influencing the variation of age at natural menopause (AANM). Estrogen receptor beta (ESR2), is an important factor in the mechanism of action of estrogen, while the aromatase gene (CYP19) and the 17-alpha-hydroxylase gene (CYP17) are involved in the biosynthesis of estrogen. We tested whether polymorphisms of ESR2, CYP19 and CYP17 genes are associated with AANM in Caucasian females. A total of 52 SNPs (17 for ESR2, 28 for CYP19, and 7 for CYP17) were successfully genotyped for 229 Caucasian women having experienced natural menopause. Comprehensive statistical analyses focusing on the association of these genes with AANM were conducted. The effects of age, height and age at menarche on AANM were adjusted when conducting association analyses. We found that six SNPs (2, 6-7, 9, 13 and 16) within ESR2 were not significantly associated with AANM after Bonferroni correction. However, two blocks of ESR2 were associated with AANM. For CYP19, two SNPs (24 and 27) were nominally associated with AANM. No significant association was observed between CYP17 and AANM. Our results suggest that genetic variation in the ESR2 and CYP19 genes may influence the variation in AANM in Caucasian women.

Genotypes of vitamin D and estrogen receptors in pre and perimenopausal women from Córdoba, Argentina

El propósito del estudio fue determinar la frecuencia de los genotipos de los receptores de vitamina D y de estrógeno y su relación con la densidad mineral ósea en mujeres sanas pre y perimenopáusicas de la ciudad de Córdoba y alrededores. Los genotipos se determinaron con la técnica de reacción en cadena de la polimerasa y análisis de los polimorfismos de longitud de fragmentos de restricción. Se usaron como restrictasas Bsm I y Fok I para el gen del receptor de vitamina D y Pvu II y Xba I para el gen del receptor de estrógeno. Se reclutaron y agruparon por edad doscientos diez mujeres pre y peri-menopáusicas. Sus niveles séricos de Ca y de hormona paratiroidea fueron similares, pero los de fósforo y b-Cross Laps disminuyeron con la edad. La densidad mineral ósea de cuello femoral disminuyó después de los 30 años. Las frecuencias genotípicas de ambos receptores fueron similares a aquéllas de otras mujeres caucásicas. No hubo asociación entre los genotipos de los receptores y la densidad mineral ósea. Los análisis de interacción entre ambos genes no evidenciaron influencia sobre la densidad mineral ósea, utilizándose edad, talla e índice de masa corporal como covariables. Los estilos de vida y hábitos de fumar y beber alcohol tampoco afectaron la densidad mineral ósea. En conclusión, estos datos no sostienen la hipótesis de que los genotipos de los receptores de vitamina D y de estrógeno influencian la densidad mineral ósea de columna lumbar y cuello femoral en mujeres sanas pre y perimenopáusicas de esta región de Argentina.

The aim of this study was to determine the frequency of vitamin D receptor and estrogen receptor genotypes and their relationship with the lumbar spine or femoral neck bone mineral density in healthy pre and perimenopausal women from Córdoba (Argentina) and adjacent areas. Genotypes were assessed by restriction fragment length polymorphism-polymerase chain reaction technique. Bsm I and Fok I for vitamin D receptor gene and XbaI and PvuII for estrogen receptor gene were used as restrictases. Two hundred and ten healthy pre and perimenopausal women were recruited and analyzed by age. Calcemia and serum parathyroid hormone did not change, but serum P and b-CrossLaps decreased with age. Femoral neck bone mineral density decreased significantly after 30 years old. Vitamin D receptor and estrogen receptor genotype frequencies were similar to those from other Caucasian women. No association between vitamin D receptor and estrogen receptor genotypes with the lumbar spine or femoral neck bone mineral density has been detected. Analysis of interaction between vitamin D receptor and estrogen receptor genes using covariates such as age, height and body mass index did not show any influence of the combination of those genotypes on bone mineral density. Lifestyle, smoking and alcohol intake had no effect on lumbar spine and femoral neck bone mineral density. To conclude, these data do not support the hypothesis that vitamin D receptor and estrogen receptor genotypes influence on lumbar spine and femoral neck bone mineral density in healthy pre and perimenopausal women from this area of Argentina.