The role of lymphocytic cells in infertility and reproductive failures in women with antiphospholipid antibodies.

BACKGROUND: The problem of pregnancy losses and infertility in autoimmune pathology is one of the most urgent problems of modern reproductive medicine. Antiphospholipid antibodies (aPL) are very often connected with reproductive failures such as miscarriage, antenatal fetal death, preeclampsia and even infertility and failure of in vitro fertilization (IVF) program. AIM: To evaluate the difference in immune status of aPL-positive women with infertility compared to healthy women and explain the possible mechanism of pathological effects of aPL, a correlation analysis between the level of aPL and the lymphocytes subpopulation was performed. STUDY DESIGN: We observed 280 women of reproductive age. Of these, 191 who met the inclusion and exclusion criteria were included in the study. All 191 women were tested for lupus anticoagulant (LA), antibodies (isotypes IgG, IgM) to cardiolipin (aCL), ß2-glycoprotein-1 (b2-GpI). Of these, 128 women had high level of aPL. The subpopulation of lymphocyte in aPL-positive women was compared with healthy women without reproductive pathology. RESULTS: In women with aPL, the absolute number of CD3+ lymphocytes, cytotoxic lymphocytes CD3+CD8+, T helpers CD3+CD4+, and the absolute levels of NK-cells and NK T-cells were significantly lower. In women with infertility and aPL circulation, we found the significantly higher absolute and relative level of CD19+ lymphocytes compared with healthy women. CONCLUSION: T-regulatory cells play an important role in inducing tolerance to fetal alloantigens and limiting the intensity of the immune response. NK cells play an important role in processes of trophoblast invasion and spiral artery remodeling. Significantly reduced level of T-cells found in women with aPL may be associated with insufficient decidualization of endometrium for embryo invasion, which is clinically manifested by IVF failure.

High-Throughput Sequencing of Circulating MicroRNAs in Plasma and Serum during Pregnancy Progression.

Although circulating microRNAs (miRNAs) in maternal blood may play an important role in regulation of pregnancy progression and serve as non-invasive biomarkers for different gestation complications, little is known about their profile in blood during normally developing pregnancy. In this study we evaluated the miRNA profiles in paired plasma and serum samples from pregnant women without health or gestational abnormalities at three time points using high-throughput sequencing technology. Sequencing revealed that the percentage of miRNA reads in plasma and serum decreased by a third compared to first and second trimesters. We found two miRNAs in plasma (hsa-miR-7853-5p and hsa-miR-200c-3p) and 10 miRNAs in serum (hsa-miR-203a-5p, hsa-miR-495-3p, hsa-miR-4435, hsa-miR-340-5p, hsa-miR-4417, hsa-miR-1266-5p, hsa-miR-4494, hsa-miR-134-3p, hsa-miR-5008-5p, and hsa-miR-6756-5p), that exhibit level changes during pregnancy (p-value adjusted < 0.05). In addition, we observed differences for 36 miRNAs between plasma and serum (p-value adjusted < 0.05), which should be taken into consideration when comparing the results between studies performed using different biosample types. The results were verified by analysis of three miRNAs using qRT-PCR (p < 0.05). The present study confirms that the circulating miRNA profile in blood changes during gestation. Our results set the basis for further investigation of molecular mechanisms, involved in regulation of pregnancy, and the search for biomarkers of gestation abnormalities.

Targeted sequencing analysis of ACVR2A gene identifies novel risk variants associated with preeclampsia.

Background: Preeclampsia (PE) is the most common complication of pregnancy that remains to be a major cause of maternal and fetal mortality. Prediction and early diagnosis of PE would allow for timely initiation of preventive therapy. According to recent studies of ACVR2A gene polymorphism is associated with PE, but it is still unclear whether these findings reflect specific pathogenetic mechanisms of this disease. Methods: We performed targeted next-generation sequencing (NGS) sequencing of ACVR2A gene by means of Ion Torrent Personal Genome machine (PGM) Sequencer. A genetic analysis of patients with PE and control group was performed. Bioinformatics analysis using Polyphen2 (Boston, MA), SIFT (La Jolla, CA), and SnpSift software were used. To select genetic markers in PE patients two additive models and score analysis were applied. Results: Based on the score analysis, we detected two substitutions (rs145399059 and rs17692648) and one insertion insAA at position 148642724 that were associated with PE in our cohorts. We also detected a variant rs17742573 that can be considered as protective against preeclampsia. Conclusions: Our data suggest that some variants in ACVR2A gene are associated with PE. But more studies are required to reveal the role of ACVR2A gene in the pathogenesis of this disease during pregnancy.