Changes in concentrations of melatonin, PlGF, and cytokines in women with preeclampsia.

Preeclampsia (PE) is a pregnancy-related disorder that significantly increases the risk of maternal and fetal morbidity and mortality. Melatonin, a potent antioxidant, has been suggested to mitigate oxidative stress and associated damage in various pathological conditions. Placental growth factor (PlGF) plays a vital role in placental development by promoting angiogenesis. This study aimed to investigate whether the levels of melatonin, cytokines, and PlGF were higher in the venous blood of women with preeclampsia during the third trimester of pregnancy compared to those with uncomplicated pregnancies. The study involved 32 women with preeclampsia and 33 healthy pregnant women as a control group. The concentrations of melatonin and PlGF were significantly lower in women with preeclampsia compared to healthy pregnant women. Specifically, the mean level of melatonin in the preeclampsia group was 30.98 pg/ml and 55.20 pg/ml in the control group (p=0.029). Similarly, the mean level of PlGF in the preeclampsia group was 40.03 pg/ml and 213.31 pg/ml in the control group (p<0.0001). This suggests that alterations in the placental production of melatonin and PlGF may contribute to the development of preeclampsia. In contrast, we observed higher levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine interleukin-10 (IL-10) in the preeclampsia group than in the control group. The mean concentration of IL-6 in the PE group was 270.79 pg/ml, whereas the control group had 224.30 pg/ml (p=0.022). Similarly, the mean concentration of IL-10 in the PE group was 41.90 pg/ml and 30.73 pg/ml in the control group (p=0.018). In women with uncomplicated pregnancies, the interaction between pro-inflammatory interleukine-6 and melatonin can be described by equality of statistical regression.

Melatonin decreases and cytokines increase in women with placental insufficiency.

Purpose: To investigate the levels of melatonin, proinflammatory and anti-inflammatory cytokines in pregnant women with placental insufficiency (PI).Materials and Methods: The PI was manifested as the intrauterine growth restriction syndrome of fetus (IUGR) in the third pregnancy trimester. The control group consisted of 20 women with uncomplicated pregnancy in the same term. The blood concentrations of melatonin, proinflammatory cytokines, such as tumor necrotizing factor-α (TNF-α), interleukin-1-ß (IL-1-ß), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4), and interleukin-10 (IL-10), were studied.Results: The concentration of melatonin was found to decrease significantly if pregnancy was complicated by intrauterine fetal growth retardation (study group -126.87 ± 14.87 pg/ml, control group -231.25 ± 21.56 pg/ml, p < .001). The levels of proinflammatory cytokines in the study group were significantly higher as compared with the control group (TNF-α: study group -10.05 ± 1.35 pg/ml, control group -5.60 ± 1.50 pg/ml, p < .05; IL-1-ß: study group -14.67 ± 2.13 pg/ml, control group -3.96 ± 0.92 pg/ml, p < .001; IL-6: study group -6.91 ± 0.99 pg/ml, control group -2.69 ± 0.99 pg/ml, p < .05). The same is true about anti-inflammatory cytokines (IL-4: study group -5.97 ± 0.50 pg/ml, control group -3.74 ± 0.62 pg/ml, p < .05; IL-10: study group -11.40 ± 1.50 pg/ml, control group -4.70 ± 3.20 pg/ml, p < .001). A moderate negative correlation between melatonin and IL-1-ß in the group with PI (r = -0.3776, p = .0097), a closed negative correlation between the same indexes in the control group (r = -0.6785, p = .001), and a moderate negative correlation between melatonin and TNF-α (r = -0.4908, p = .02) were found.Conclusions: The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. Strengthening of the proinflammatory immunity shown as the increasing of the levels of TNF-α, IL-1-ß, and IL-6 levels is also present in case of IUGR. Increase of the serum concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of compensatory mechanisms, which decrease the risk of premature labor.

Melatonin 1A and 1B Receptors' Expression Decreases in the Placenta of Women with Fetal Growth Restriction.

Melatonin and its metabolites prevent oxidative stress and apoptosis, and it is actively produced by the placenta during pregnancy. Melatonin 1A and 1B receptors are present in human villous trophoblastic cells. We aimed to investigate the expression of melatonin 1A and 1B receptors in human placental tissue in the case of placental insufficiency manifested as the intrauterine growth restriction syndrome of the fetus (IUGR). Thirty-two pregnant women aged 18-36 with placental insufficiency manifested at the term 36 weeks of gestation as the IUGR syndrome (the estimated fetal weight less than the 3rd percentile) were included in the experimental group; all their babies had the diagnosis confirmed at birth, which occurred after 37 weeks of gestation. The control group consisted of 30 women with uncomplicated pregnancy of the same term. Pieces of the placental tissue were obtained after deliveries, and melatonin 1A and 1B receptors were immunoassayed; the richness of melatonin receptors in the placental tissue was estimated on the basis of immunohistochemical (IHC) staining of receptors, calculated in the IHC image score. The optical density of melatonin 1A receptors in the placentas obtained from women whose pregnancies were complicated with IUGR was significantly lower than that in the placentas from uncomplicated pregnancies: generally in the trophoblast, it was 0.095 ± 0.0009 IHC image score (in the control group, 0.194 ± 0.0015, p < 0.0001); in the apical parts of the syncytiotrophoblast, 0.108 ± 0.0016 IHC image score (in the control group, 0.221 ± 0.0013, p < 0.0001); and in the stromal cells of placental villi, 0.112 ± 0.0013 IHC image score (in the control group, 0.156 ± 0.0011, p < 0.0001). The optical density of melatonin 1B receptors in placentas obtained from women whose pregnancies were complicated with IUGR was also lower than that in the placentas from uncomplicated pregnancies: generally in the trophoblast, it was 0.165 ± 0.0019 IHC image score (in the control group, 0.231 ± 0.0013, p < 0.0001), and in the apical parts of the syncytiotrophoblast, 0.188 ± 0.0028 IHC image score (in the control group, 0.252 ± 0.0009, p < 0.0001). There was no difference found in the optical density of melatonin 1B receptors in the stromal cells of placental villi between the two groups: in the experimental group, 0.109 ± 0.006 IHC image score, and in the control group, 0.114 ± 0.0011 (p = 0.65). Melatonin receptors 1A and 1B are significantly less expressed in the placental tissue in the case that pregnancy is complicated with placental insufficiency, manifested as the intrauterine growth restriction syndrome of the fetus.

Expression and Significance of Matrix Metalloproteinase-2 and Matrix Metalloproteinas-9 in Endometriosis.

Endometriosis is a chronic benign hormone-dependent condition when the endometrial tissue, identical with the endometrium by its morphological and functional properties, grows outside the borders of the uterine mucous membrane. Recent studies have pointed to the possible role of matrix metalloproteinases (MMPs) in the pathogenesis of endometriosis. We suggested a hypothesis that increased expression of MMPs activity in eutopic and ectopic endometrium of patients with endometriosis might correlate with the presence of endometriotic lesions. The aim of the study was to evaluate the level of MMP-2 and MMP-9 expression in the ectopic endometrium of women with visible endometriotic lesions and eutopic endometrium in patients with no signs of endometriosis. The study was conducted on 43 patients. They were divided into two groups. Group 1 included 31 patients with peritoneal/ovarian endometriosis who had undergone laparoscopy and hysteroscopy. Group 2 consisted of 12 patients with leiomyoma, endometrial polyps or relatively healthy patients who had undergone hysterectomy or polypectomy and endometrial curettage. This study showed statistically higher expression of MMP-2 (1.7783 ± 0.22 immunohistochemistry (IHC) optical density score compared to the control group - 1.41± 0.34, p = 0.0017) and MMP-9 (1.352 ± 0.067 versus 1.85 ± 0.26 in the control group, p = 0.001) in ectopic and eutopic endometrium samples from patients with endometriosis compared to samples taken from patients without endometriosis. A strong correlation between expression of the above-mentioned MMPs (r=0.74 for MMP-2 and r=0.88 for MMP-9) in ectopic and eutopic endometrium might be of promising diagnostic value.

Melatonin Levels Decrease in the Umbilical Cord in Case of Intrauterine Growth Restriction.

Intrauterine growth restriction (IUGR) is a common reason for perinatal morbidity and mortality. Also, it is often complicated with fetal distress. Melatonin is widely known as an anti-oxidant agent, and it might decrease the damage of tissues caused by hypoxia. It is also known that levels of pro- and anti-inflammatory cytokines are changed during pregnancy. Placental growth factor (PlGF) is responsible for the angiogenesis in the placenta. We aimed to investigate whether the level of melatonin, cytokines, and PlGF in umbilical blood after birth is different in the case of IUGR compared to normal fetuses. Fourteen women whose pregnancies were complicated with IUGR were included in the study group. The presence of IUGR was confirmed by ultrasound fetometry in the third pregnancy trimester, 30-36 weeks of gestation. All patients delivered their children vaginally after 37 weeks of pregnancy. The cases of severe fetal distress that required a caesarian section, obstetrical forceps, or vacuum extraction of the fetus were excluded from the study. We found that the concentrations of cytokines did not differ significantly between the groups. Also, no significant difference in the daytime of delivery was found between the groups. The concentrations of melatonin and PlGF in the umbilical blood at labor were significantly lowered in the case of IUGR compared to normal pregnancies. This fact, as we consider, is caused by altered production of melatonin and PlGF by the placenta. Therefore, the protective action of these two factors for the fetus at labor is decreased in IUGR.