ESTRTOGENE AT EARLY PREGNANCY WITH HERPES-VIRUS EXACERBATION

Decrease of estriol and estradiol concentration, was found, at herpes-viral infection exacerbation, in placenta of pregnant at early stages of gestations. Revealed, change was shown by result of defect of base steroid. — cholesterol content, as well as distribution, of the steroid, hormone syntheses process: low activity of placental 17β-hydroxysteroid dehydrogenase and. inadequacy steroidogenesis regulating mechanism.

DISTURBANCE OF THE PROGESTERONE AND ITS METABOLITES SYNTHESIS IN THE DEVELOPMENT OF NEUROLOGICAL DISORDERS IN CHILDREN AFTER CYTOMEGALOVIRUS INFECTION DURING PREGNANCY

Cytomegalovirus (CMV) infection is one of the causes of congenital neurological disorders and the virus itself is the most common viral  agent causing an imbalance in the production of placenta  progesterone and its neuroactive metabolites – allopregnenolone and 5α-dihydroprogesterone. The aim was to evaluate the concentration  of progesterone and its metabolites – 5α-dihydroprogesterone and  allopregnenolone – in placenta during exacerbation of CMV infection  in the first trimester of pregnancy, and the impact of these  disturbances on the development of neurological disorders in children. We examined 30 pregnant women with exacerbation of  CMV infection in the first trimester of pregnancy and 30 pregnant  women with latent disease; and later their newborns. The enzyme  immunoassay was used to determine  concentration of progesterone  in placenta; the histochemical method – to determine 5α-dihydroprogesterone and allopregnenolone. Newborns underwent  neurosonography studies. Exacerbation of CMV infection in the first  trimester of pregnancy decreased progesterone in placenta by 1.3  times, 5α-dihydroprogesterone – by 1.73 times and allopregnenolone – by 2 times. Ultrasound examination of the brain  showed ventriculomegaly, periventricular ischemia, and pseudocysts  in newborns up to one year from mothers with exacerbation of CMV  during pregnancy. Later, minimal brain dysfunctions were manifested by motor disorders, increased general, vegetative excitability, and a  tendency to digestive and sleep disorders. The data obtained  indicate that the exacerbation of CMV infection in the first trimester  of pregnancy is interrelated with a decrease in the concentration of progesterone and its metabolites (5α-dihydroprogesterone, allopregnenolone) in the placenta and development of neurological dysfunction in newborns

Effect of Oxidative Stress and Fatty Acids Disbalance on the Development of Apoptosis in the Placenta with Cytomegalovirus Infection in the First Trimester

Background. Reactivation of cytomegalovirus infection (CMV) during pregnancy is associated with manifestation of oxidative stress, both in the maternal peripheral blood and in the placental tissues. One of the effects of oxidative stress is a disturbance of the metabolism of fatty acids, which leads to the initiation of the apoptotic cascade, the death of trophoblast cells and, as a result, tissue or organ dysfunction, promoting to the development of a pathological condition. However, an analysis of the current literature indicates insufficient information on this problem in the villous chorion of the placenta in CMV infection.Aims. To study the relationship between the oxidative stress development and fatty acid imbalance in apoptosis of trophoblast cells during reactivation of CMV in the first trimester.Material and methods. We examined peripheral blood, urine, a homogenate of the villous chorions from 35 pregnant women with CMV reactivation within 9–11 weeks of pregnancy and from 30 pregnant women without CMV of the same gestation period. We studied levels of IgM and IgG for cytomegalovirus, low-avid IgG antibodies to cytomegalovirus (avidity index), phospholipase A2 content, fatty acid content, number of apoptotic trophoblast cells, fatty acid peroxide content and catalase activity. Sampling and analysis of material from pregnant women was conducted in 2016–2018.Results. The reactivation of CMV in the first trimester of pregnancy led to an increase content in the phospholipase A2 in villous chorion by 2.5 times, by 1.5 times of fatty acid peroxides, 1.5 times arachidonic acid, palmitic acid by 1.3 times, number of trophoblast cells in a state of apoptosis by 4.7 times and decrease catalase activity by 1.44 times.Conclusion. As a result of the study, cytomegalovirus-dependent induction of oxidative stress and imbalance of fatty acids triggering apoptosis of trophoblast cells was identified. Increased apoptosis initiates inflammation and destructive processes in the early placenta

Особенности вазоактивной регуляции в ворсинчатом хорионе у женщин с самопроизвольным абортом и активной цитомегаловирусной инфекцией

The aim of the study was to assess the levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), and vascular endothelial growth factor A (VEGF-A) in tissue extracts in comparison with the histologic examination of the endometrium and chorionic villi in women with spontaneous abortion and active cytomegalovirus (CMV) infection.Materials and methods. 81 women at 7–9 weeks of pregnancy were examined: of them, 51 women were CMVseropositive with active infection and after spontaneous abortion, and 30 patients were CMV-seronegative, healthy women after therapeutic abortion. Immunoglobulins (Ig) M and G to CMV and CMV IgG avidity were measured in the blood plasma; sFlt1, PlGF, and VEGF-A were determined in extracts of chorionic villi by enzyme immunoassay. CMV DNA was detected in mononuclear cells of peripheral blood, urine, and chorionic villi by real-time polymerase chain reaction (PCR). A histologic examination of the endometrium and chorionic villi was carried out.Results. In chorionic villus extracts of women with spontaneous abortion and active CMV infection, the concentration of sFlt1 was 3.25 times higher (p < 0.001), and the levels of PlGF and VEGF-A were 1.31 (p < 0.001) and 2.16 times lower (p < 0.001) than in healthy women. A strong negative correlation was established between the levels of sFlt1 and PlGF (r = –0.702; p < 0.001) and VEGF-A (r = –0.858; p < 0.0005), and a positive correlation was revealed between PlGF and VEGF-A levels (r = 0.860; p < 0.001). According to the data of the histologic examination, a lag in decidual transformation of uterine vessels, trophoblast invasion, growth and differentiation of villi, and formation of fetal circulation was detected.Conclusion. The mechanisms of spontaneous abortion in women with active CMV infection include an imbalance of pro- and anti-angiogenic factors, which causes impaired placental development and uteroplacental circulation.Цель. Оценить содержание растворимого рецептора fms-подобной тирозинкиназы (sFlt1), плацентарного фактора роста (PlGF) и васкулоэндотелиального фактора роста (VEGF-А) в тканевых экстрактах в сопоставлении с гистологией слизистой оболочки матки и ворсинчатого хориона у женщин с самопроизвольным абортом и активной цитомегаловирусной (ЦМВ) инфекцией.Материалы и методы. Обследована 81 женщина в период с 7-й по 9-ю нед беременности: 51 ЦМВ-серопозитивная с самопроизвольным абортом и активной инфекцией и 30 серонегативных здоровых женщин с медицинским абортом. В плазме крови определяли иммуноглобулины (Ig) класса М и G к ЦМВ, авидность ЦМВ-IgG; в экстрактах ворсинчатого хориона – sFlt1, PlGF, VEGF-А методом иммуноферментного анализа. В мононуклеарных клетках крови, пробах мочи, ворсинчатом хорионе методом полимеразной цепной реакции в режиме реального времени выявляли ДНК ЦМВ. Проводили гистологическое исследование слизистой оболочки матки и ворсинчатого хориона.Результаты. В экстрактах ворсинчатого хориона у женщин с самопроизвольным абортом и активной ЦМВ-инфекцией концентрация sFlt-1 была выше в 3,25 раза (р < 0,001), PlGF и VEGF-А – ниже в 1,31 (р < 0,001) и 2,16 раза (р < 0,001), чем у здоровых женщин. Установлена сильная обратная корреляционная связь между уровнями sFlt-1 и PlGF (r = –0,702; р < 0,001) и VEGF-А (r = –0,858; р < 0,0005), прямая связь – PlGF и VEGF-А (r = 0,860; р < 0,001). По данным гистологического исследования, отмечено отставание в децидуализации и трансформации маточных сосудов, инвазии трофобласта, роста и дифференцировки ворсин, формирования фетальных сосудов.Заключение. К механизмам самопроизвольного аборта у женщин с активной ЦМВ-инфекцией можно отнести дисбаланс анти- и проангиогенной регуляции, вызывающий ограничение развития плаценты и маточно-плацентарного кровообращения.