No 4 (2019)

The paper analyzes the works of Russian and foreign scientists on placental mitochondrial dysfunction as one of the possible causes of the occurrence and development of pregnancy complications. There is a lot of evidence suggesting that the pathogenesis of preeclampsia, intrauterine growth restriction, preterm birth, and miscarriages is closely related to oxidative stress, proteomic spectrum changes, lipid metabolic disorders, impaired miRNA expression, quality-control system dysregulation, and lower respiratory chain enzyme activity, which occur in placental mitochondria. Although the pathophysiology underlying gestational complications is different, the changes in mitochondrial structure and functions are seen in all cases of a common final stage of cell death and can be a target for pharmacotherapy.

The molecular mechanisms of the pathogenesis of gestational diabetes mellitus (GDM) remain insufficiently studied, which is largely determined by its heterogeneous nature. The paper reviews the data available in the current literature on studies of the molecular genetic determinants of the development of gestational diabetes mellitus. It describes predictors for GDM, their relationship to obstetric and neonatal outcomes, as well as associations with other types of diabetes and with the risk of their development. Conclusion. Further investigations are needed to identify virtually significant molecular genetic biomarkers for GDM.

Objective. To determine an association of the polymorphic variant G-105A of the SEPS1 gene and the polymorphic variant C3872T of the CRP gene with preterm birth in European women. Subjects and methods. Sixty-five women with preterm birth at 23.5 to 37 weeks’ gestation and 65 women with full-term pregnancy were genotyped. The polymorphic variant G-105A of the SEPS1 gene was determined by the polymerase chain reaction (PCR), followed by restriction analysis, the polymorphic variant C3872T of the CRP gene was done by the allele-specific PCR followed by electrophoretic detection. Results. There was an association of the polymorphic variant G-105A of the SEPS1 gene with the risk of preterm birth in Caucasian women. The frequency of the A allele of the SEPS1 gene was 20%, which was signif icantly higher than that in the control group (8%) (х2 = 5.025, p = 0.025). The incidence of heterozygotes was also considerably higher in the preterm birth group (x2 = 6.002; p = 0.014).There was no association of the T allele in the polymorphic variant C3872T of the CRP gene with preterm birth. Conclusion. The A allele in the polymorphic variant G-105A of the gene SEPS1 can act as one of the predictors of preterm birth.

Objective. To investigate the incidence of chronic cervicitis (CC), detection rates of various types of human papillomavirus (HPV), the significance of the viral load, expression of mRNA genes involved in regulating the cell cycle, apoptosis, immunity, matrix metalloproteinases, and the methylation of the WIF1 gene promoter region among patients with CC associated with HPV infection. Material and methods. The study comprised 202 patients aged from 25 to 49 years. A comprehensive clinical and laboratory examination included patient history taking, gynecological examination, colposcopy, HPV testing, liquid-based cytology and targeted cervical biopsy (according to indications), vaginal smear microscopy, assessment of vaginal microbiocenosis, analysis of the transcriptional profile of KI67 genes KI67, CDKN2A, BCL2, PGR, IFNAR1, IL1RN, CCND1, EGFR, IL1B, IL10, IL18, TNFA, GATA3, TLR4, CD68, TGFB1, CXCL5, CXCL10 CXCL13, mMp8, mMp9, and the determination of the methylation level of the WIF1 gene promoter region. Results. Among patients with cervical pathology, 25.7% were found to have HPV-associated CC. The most commonly detected types were 16, 33, 35, and 66. The presence of HPV infection in endocervical scrapings was associated with a 1.8- and 2.4-fold higher expression of mRNA of CDKN2A/ p16 gene and IL10, respectively (p < 0.05). The inflammatory process was accompanied by a 1.5 to 2.9 - fold increase in the expression of mRNA of IFNAR1, IL1B, IL10, TNFA, TLR4, CD68, TGFB1 and MMP9 genes (p <0.05). In the study cohort, the methylation of the WIF1 gene was either not observed or weakly expressed. Conclusion. The genes IFNAR1, IL1B, IL10, TNFA, TLR4, CD68, TGFB1, and MMP9, may be suggested as markers for CC. The presence of HPV contributes to an increase in the expression of mRNA of the CDKN2A/p16 genes and the immunosuppressive IL10.

Objective: to study associations of ESR1 rs3020394 and rs1884051 and ESR2 rs4986938polymorphisms with the development of endometrial hyperplasia. Subjects and methods. The study included 1501 women: 520patients with simple endometrial hyperplasia and 981 control-group individuals. ESR1 rs3020394 and rs1884051 and ESR2 rs4986938polymorphisms were genotyped. Results. ESR2 rs4986938 polymorphism was established to be associated with the development of endometrial hyperplasia. The A/A genotype is a risk factor for the development of the disease (OR = 1.43). ESR2 rs4986938 polymorphism had substantial regulatory effects (it was located in the region of histones that marked enhancers in 17 different organs and tissues, at the DNase I hypersensitive sites in 6 tissues, in the DNA regulatory motif regions that were binding sites of 5 transcriptional factors (CTCF_known1, Nr2f2, Pax-61, Pax-81, and RAR) and affected the expression of the ESR2, SYNE2, and MTHFD1 genes. Conclusion. ESR2 rs4986938 polymorphism is associated with the development of endometrial hyperplasia.

Combined oral contraceptives (COCs) are one of the most effective hormonal contraceptive drugs. Voluntary conscious choice of a particular method is an important guiding principle; and counseling plays a fundamental role in the successful use of contraceptive methods. A number of side effects of COCs limit their use in certain categories of patients. The use of WHO recommendations for each nosological entity (the 2015 medical eligibility criteria for using contraceptive methods) assists in individualizing the choice of a contraceptive and in avoiding serious risks. It should be noted that the use of a COC makes it possible to obtain the necessary therapeutic and/or prophylactic effect in addition to its contraceptive one.

Endometrial hyperplastic processes are the most common indications for intrauterine interventions and often for hysterectomy. It has been previously proven that a therapeutic approach to treating endometrial hyperplasia (EH) is in fact anti-recurrent after histological evaluation of a removed substrate. EH therapy using a GnRH agonist has been pathogenetically substantiated by the proven multiple mechanisms of action: from desensitization of the pituitary gland to interaction with specific receptors in endometrial cells. The offensive potential of currently available combined oral contraceptives in the prevention of recurrent EH in reproductive-aged patients who are not planning to become pregnant after a therapy cycle with a GnRH is determined primarily by the tropism of the gestagen included in the drug for the endometrium.

Background. Cystinuria is an autosomal recessive hereditary disease associated with impaired transport of dibasic amino acids (including cystine) and with the formation of coral renal calculi, which is accompanied by frequent surgical interventions and recurrent pyelonephritis. Case report. A primigravida patient was hospitalized for a period of29-30 weeks with an exacerbation of chronic pyelonephritis of only one right working kidney. Combination treatment made it possible to prolong pregnancy up to 34 weeks. Early delivery is due to signs of renal failure. Conclusion. Strict adherence to the rules of management of pregnant women with only one working kidney in the presence of chronic pyelonephritis could delay delivery to an optimal period in terms of minimizing perinatal complications.

Background. Pelvic floor muscle failure (PFMF) that is manifested by perineal incompetence is concurrent with vaginal dysbiosis in 79% of cases and often has a polymicrobial etiology, which requires appropriate treatment. Case report. The paper describes a clinical case of a female patient diagnosed with PFMF (N81.8). This patient underwent smear microscopy, pH-metry, and evaluation of pelvic floor muscle strength; questionnaires were used. Treatment was performed, which included the combination drug metronidazole/miconazole/lidocaine/viseptol and stimulator-based pelvic floor muscle training. Treatment for dysbiosis was effective when the above drug was administered; there were no recurrences during the follow-up period. Stimulator-based treatment for PFMF could reduce the frequency and severity of symptoms (from 94.8 to 69.8 PFDI-20 scores; p = 0.03) and dyspareunia (from 80 to 20 visual analogue scale scores; p = 0.03), improve sexual function (from 15.3 to 27.2 FSFI scores; p = 0.001), and prevent progressive PFMF and recurrent dysbiosis. Conclusion. The described clinical case showed that the combination treatment of perineal incompetence with the use of stimulators during the pregravidpreparation period could reduce the incidence and severity of symptoms of stress urinary incontinence and dyspareunia, prevent postpartum progressive PFMF, as well as recurrent vaginal dysbiosis, and improve sexual function.