Molecular-genetic and epigenetic aspects of impaired endometrial receptivity in women with low birth weight
Objective. To study the molecular-genetic and epigenetic mechanisms of impairment of endometrial receptivity in patients with reproductive failures born with low weight. Patients and methods. We examined 96 adolescent girls suffering from abnormally developing menstrual function, namely, abnormal uterine bleeding, and 210 women of reproductive age suffering from uterine factor infertility or pregnancy loss associated with a «thin» endometrium. All patients were born full term. In the main cohorts, patients were stratified depending on birth weight. We analysed clinical data, medical histories and molecular-genetic examinations of polymorphic variants in genes of sex steroid receptors, genes regulating endothelial function, angiogenesis and thrombophilia by the allele-specific real-time polymerase chain reaction method with analysis of the melting curves of amplification products with the use of the reagent kit and protocols of the company LLC «Test Gene» (Russia). Results. A risk of reproductive failures conditioned by impaired endometrial receptivity is associated with carriage of polymorphic allele А of gene VEGF 2578C>A (for infertile patients OR = 2.73 (1.36-5.45); р = 0.01, with pregnancy loss -OR = 4.61 (2.19-9.71); р = 0.01) and with carriage of polymorphic allele 675 4G of gene PAI-1 675 5G>4G (for infertile patients OR = 8.45 (3.96-18.21); р = 0.001, with pregnancy loss - OR = 9,.8 (4.61-21.74); р = 0.001). Carriage of polymorphism pVull-СС of gene ESR1 397T>C is associated with an enhanced risk of the formation of abnormal menstrual function, manifested by abnormal uterine bleeding of puberty (OR = 4.58 (0.97-21.68); р = 0.04), and a risk for developing pregnancy loss conditioned by a «thin» endometrium when reaching the reproductive age (OR = 6.79 (1.94-23.75); р = 0.01). In women born with low weight, a significantly higher frequency of genotypes containing polymorphic allele 786С of the endothelial NO-synthase gene NOS3 786T>C can be traced: for infertile women OR = 6.173 (1.83-20.83); р = 0.001; for women with pregnancy loss OR = 4.902 (1.69-14.08); р = 0.002; for girls OR = 2.56 (1.01-6.50); р = 0.04. Conclusion. The genetic network containing the described variation alleles coordinates the pathological character of regulation of endometrial function, which might result in the formation of a «thin» nonreceptive endometrium in response to its traumatic injury.