Fetal left ventricular myocardial performance index measured at 11-14 weeks of gestation in fetuses with an increased nuchal translucency.

OBJECTIVE: This study aimed to evaluate the effect of an increase in nuchal translucency (NT) thickness on the myocardial performance index (MPI) in fetuses without cardiac anomaly in the first trimester and to determine whether a difference in MPI between those with and without trisomy 21 in these fetuses could be determined. METHODS: The study group consisted of 53 pregnancies complicated with increased NT thickness without any associated structural anomalies. Forty-six gestational age-matched pregnant women whose fetuses had normal NT thickness were enrolled as the control group. RESULTS: In the increased NT thickness group, the mean isovolumetric relaxation time (IRT) value (0.050 ± 0.011 s) was significantly higher and the mean ejection time (ET) value (0.149 ± 0.010 s) was significantly lower than those values in the normal NT thickness group (0.045 ± 0.005 and 0.155 ± 0.009 s, p = 0.023 and p = 0.009, respectively). We found a significantly higher mean left MPI value in the increased NT thickness group (0.574 ± 0.153) versus the normal NT thickness group (0.487 ± 0.107, p < 0.001). Within the increased NT thickness group, the mean left MPI value was similar in the fetuses with normal karyotype and those with trisomy 21 (p = 0.419). CONCLUSION: We demonstrated a significantly greater mean MPI value in the increased NT thickness group than in the normal NT thickness group. Within the increased NT thickness group, no differences in the left MPI value in the fetuses with normal karyotype and the fetuses with trisomy 21 were found.

Maternal Serum Cripto-1 Levels in Pregnancies Complicated with Placenta Previa and Placenta Accreta Spectrum (PAS).

OBJECTIVE: To examine maternal serum Cripto-1 levels in placenta accreta spectrum (PAS) pregnancies and compare them with placenta previa (PP) cases and healthy pregnancies. STUDY DESIGN: A prospective case-control study. PLACE AND DURATION OF STUDY: Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey, from April to September 2021. METHODOLOGY: Sixty singleton pregnant patients with PP complicated with PAS were enrolled, 45 singleton pregnant women with a diagnosis of PP without PAS, and 48 healthy uncomplicated gestational age-matched singleton pregnant women. Cripto-1 levels were determined and evaluated. RESULTS: The median maternal serum concentrations of Cripto-1 were greater in pregnant women with PAS (3.11 ng/mL) than in the PP (2.52 ng/mL) and the control groups (2.01 ng/mL, p<0.001). Based on the Youden index, a 2.557 ng/mL cut-off value of maternal serum Cripto-1 level had a 76.7% sensitivity and 72.1% specificity to diagnose pregnancies complicated with PAS. A negative and statistically significant linear relationship was found between maternal serum Cripto-1 concentration and the gestational week at birth (r= -0.325, p<0.001). A positive and statistically significant linear relationship was found between maternal serum concentrations of Cripto-1 and maternal length of hospital stay after birth (r= 0.320, p<0.001). CONCLUSION: Serum Cripto-1 levels were significantly increased levels in pregnant women suffering from PAS than in pregnant women with PP and uncomplicated healthy pregnancies. Higher expression of Cripto-1 might be a crucial factor in the pathogenesis of PAS. KEY WORDS: Abnormal placental implantation, placenta accreta spectrum, Cripto-1, Placenta previa.

Serum autotaxin levels correlate with the severity of pruritus in intrahepatic cholestasis of pregnancy.

PURPOSE: This study aimed to examine autotaxin (ATX) concentrations in the serum of pregnant women complicated with intrahepatic cholestasis of pregnancy (ICP) and compare them with individuals with uncomplicated healthy pregnancies. METHODS: This prospective case-control study took place with 83 pregnant women. The study group included 43 pregnant women presenting with a singleton pregnancy diagnosed with ICP in their third trimester of pregnancy. The diagnostic power of the ATX variable was examined by receiver operating characteristic analysis, and the cut-off value calculated according to the Youden index was summarized with the related sensitivity and specificity points. RESULTS: The mean serum concentration of maternal ATX was significantly higher in the ICP cases (8.91 ± 2.69 pg/mL) compared to the pregnant women in the control group (3.59 ± 1.39 ng/mL, p < 0.001). According to the Youden index, a 5.80 ng/mL cut-off value of serum ATX concentrations can be used to diagnose ICP with 97.7% sensitivity and 97.5% specificity. A significant highly positive correlation was found between maternal serum ATX levels and maternal serum total bile acid levels (r = 0.633 and p < 0.001) and itch intensity, which was objectified by the visual analog scale score (r = 0.951 and p < 0.001). CONCLUSION: Maternal serum ATX levels were significantly increased in ICP patients as compared with healthy pregnant women. Also, serum ATX activity was highly correlated with the itch intensity. We consider that ATX might represent a robust, accurate, and reliable circulating biomarker to diagnose ICP.

A novel marker endoplasmic reticulum to nucleus signalling-1 in the diagnosis of gestational diabetes mellitus

Objective: We aimed to investigate maternal plasma endoplasmic reticulum to nucleus signalling-1 (ERN-1) concentrations in patients diagnosed with gestational diabetes mellitus (GDM). Material and Methods: This was a cross-sectional study of 57 pregnant women with GDM and 40 gestational age- and body mass index-matched, healthy pregnant controls, conducted between August 2020 and November 2020. Plasma ERN-1 levels, other laboratory markers of insulin resistance, and demographic characteristics were compared between groups. Results: Fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), hemoglobin A1c and plasma ERN-1 levels were significantly higher in the GDM group than in the healthy controls (p<0.001). Positive correlation was found between ERN-1 levels and HOMA-IR values (p=0.016). The optimal cut-off value for ERN-1 to diagnose GDM was 6.960 ng/mL, with a sensitivity of 78.9% and a specificity of 75.0% (p<0.001). Conclusion: ERN-1 may be considered as a new marker for diagnosis of GDM and may also be a potential target in studies of GDM treatment modalities.

Fetal intracranial hemorrhage: prenatal sonographic diagnosis criteria and postnatal outcomes

Objective: The aim of this study was to improve knowledge of prenatally diagnosed fetal intracranial hemorrhage (ICH), defining the ultrasound (US) examination results, the contribution of fetal magnetic resonance imagination (MRI) to the diagnosis, and the pregnancy outcomes, from a series of fetal ICH cases. Material and Methods: This retrospective, observational study included eleven fetuses diagnosed with ICH from April 2016 to August 2020. The data regarding the medical records, prenatal US and MRI findings, treatment, and prognosis of fetal ICH cases were collected from the hospital database and analyzed. Results: Fetal ICHs were grade 3 in six cases, and grade 4 in the remaining five cases. The mean gestational age at diagnosis was 30.2 weeks. Nine (81.8%) of the cases were diagnosed in the third trimester and two (18.2%) in the second trimester. Fetal cranial MRI was performed in 7/11 (63.6%) following ultrasonographic diagnosis. MRI confirmed fetal ICH diagnosis and previous US findings regarding location and grade in all cases. Five patients (45.5%) diagnosed with grade 3 (n=1) and grade 4 (n=4) ICH underwent pregnancy termination. Of the remaining six cases, one (9.1%) diagnosed with grade 3 fetal ICH resulted in an intrauterine fetal demise. Four cases classified as grade 3 fetal ICH and one case with grade 4 fetal ICH were born alive at term. Conclusion: The clinical manifestations of fetal ICH are diverse and have a wide spectrum of severity and prognostic implications. Fetal ICH cases were mainly detected in the third trimester, with a minority detected in the second trimester. These cases can be safely diagnosed and graded by US examination, but the underlying etiology frequently cannot be determined. Fetal cranial MRI may aid in diagnosis confirmation if this is unclear from US in order to provide appropriate counseling to the parents.

Increased maternal serum aquaporin 9 levels in pregnancies complicated with gestational diabetes mellitus.

INTRODUCTION: This study aimed to examine maternal serum aquaporin 9 levels in pregnant women with gestational diabetes mellitus and to compare them with non-diabetic pregnant women. METHODS: Forty-one pregnant women between 37 and 39 weeks of gestation complicated with gestational diabetes mellitus and 39 non-diabetic pregnant women at similar gestational weeks without additional obstetric complications were included in this cross-sectional study. Maternal serum aquaporin 9 levels and leptin levels of the cases were measured. RESULTS: Maternal serum leptin and aquaporin 9 levels in pregnant women with GDM were found to be significantly higher than in the control group (p < .001). In the study group, first-minute Apgar scores were significantly lower and birth weight significantly higher (p = .001 and .005, respectively). A weak but significant positive correlation between aquaporin 9 levels and maternal body mass index (r = 0.279, p = .012), birth weight (r = 0.433, p < .001), and hemoglobin A1c (r = 0.354, p = .001) levels was detected. A significant positive correlation was detected between maternal serum aquaporin 9 levels and leptin levels (r = 0.331, p = .003). CONCLUSION: The increased aquaporin 9 levels detected in cases with gestational diabetes mellitus might be a marker of the poor maternal metabolic environment specific to diabetes and might contribute to the pathophysiology of gestational diabetes.

Should isolated aberrant right subclavian artery be ignored in the antenatal period? A management dilemma

Objective: To investigate the frequency and types of chromosomal abnormalities in fetuses with the aberrant right subclavian artery (ARSA) and to evaluate its association with other ultrasonographic findings. Materials and Methods: In all, 11,666 fetal anatomic surveys were performed between March 2014 and March 2020. The cases diagnosed as ARSA were examined. Accompanying ultrasound findings and chromosomal abnormalities were collected. Results: ARSA was detected in 140 fetuses (1.2%). The ARSA appeared isolated in 47.1% (66/140) of cases and the remaining 52.9% (74/140) of cases were associated with cardiac or extracardiac malformations and soft markers. Chromosomal abnormalities were detected in 17.8% (25/140) of all cases. Trisomy 21 was the most common chromosomal anomaly with a prevalence of 11.4% (16/140). The corresponding rate was 3% (2/66) and 18.9% (14/74) for isolated and non-isolated ARSA, respectively. DiGeorge syndrome was detected in 3% (n=2) and Turner syndrome was in 3% (n=2) of the isolated group. ARSA was not an isolated finding in any of the 4 fetuses with trisomy 18. Conclusion: Isolated ARSA may be the only antenatal predictor of trisomy 21 or other chromosomal anomalies, including DiGeorge or Turner syndrome. Hence, visualization of the right subclavian artery should be a part of the fetal anatomic survey and genetic analysis should be recommended even in the absence of associated findings.

Maternal serum IL-22 concentrations are significantly upregulated in patients with preterm premature rupture of membranes.

OBJECTIVES: This study aimed to compare the serum IL-22 levels between preterm premature rupture of membranes (PPROM) patients and the control group with intact membranes. We also hypothesized whether serum IL-22 upregulation might contribute to defense against inflammatory responses and improve the pregnancy outcomes. MATERIAL AND METHODS: We performed this prospective case-control study between 24-34 weeks of pregnancy. We enrolled 40 singleton pregnant patients with PPROM and 40 healthy gestational age- and gravidity-matched patients without PPROM. The degree of association between variables and IL-22 were calculated by Spearman correlation coefficients where appropriate. Scatter plots were given for statistically significant correlations. ROC curve was constructed to illustrate the sensitivity and specificity performance characteristics of IL-22, and a cutoff value was estimated by using the index of Youden. RESULTS: Maternal serum IL-22 levels were significantly higher in PPROM patients (60.34 ± 139.81 pg/mL) compared to the participants in the control group (20.71 ± 4.36 pg/mL, p < 0.001). When we analyze the area under the ROC curve (AUC), the IL-22 value can be considered a statistically significant parameter for diagnosing PPROM. According to the Youden index, a 23.86 pg/mL cut-off value of IL-22 can be used to diagnosing PPROM with 72% sensitivity and 61.5% specificity. There was no positive correlation between serum IL-22 levels and maternal C-reactive protein (CRP) value, procalcitonin value, latency period, birth week, birth weight, and umbilical cord blood pH value. CONCLUSIONS: Maternal serum IL-22 levels were significantly higher in PPROM patients than healthy pregnant women with an intact membrane. We suggest that IL-22 might be a crucial biomarker of the inflammatory process in PPROM.

Blake's pouch cyst: Prenatal diagnosis and management.

OBJECTIVE: This study aimed to present the characteristic features of 19 patients who were diagnosed as having Blake's pouch cyst (BPC) at our center. MATERIALS AND METHODS: Nineteen patients diagnosed as BPC between 2015 and 2019 were included in this retrospective study. Follow-up examinations were performed using ultrasonography (US) every three weeks up to 35 weeks of gestation. Prenatal magnetic resonance imaging (MRI) was performed at the time of diagnosis or during follow-up in 13 patients. MRI or transfontanellar US was performed to confirm the diagnosis of BPC after delivery. Karyotype results of eight patients were recorded. RESULTS: Isolated BPC was observed in 9 (47%) patients, and associated anomalies were detected in 10 (53%) patients, including seven (36%) with the central nervous system and four (21%) with cardiac anomalies. Two fetuses had abnormal karyotype analysis as trisomy 21 and 13. The MRI report of eight patients was "differential diagnosis required for Dandy-Walker complex" and only in five (26%) patients, it was reported to be compatible with BPC. Spontaneous resolution was seen in four patients. Postnatal MRI was performed in five patients, and transfontanellar US in two patients, and all MRI and US results were consistent with BPC. During the neonatal period, abnormal neurologic development was observed in four (21%) patients, and one (5%) died. CONCLUSION: Although the prognosis of isolated BPC is very good with healthy neurologic development until advanced ages, death in the early neonatal period and abnormal neurologic development may be observed depending on the condition of the associated anomalies.

Maternal near-miss patients and maternal mortality cases in a Turkish tertiary referral hospital.

OBJECTIVES: This study aimed to estimate the incidence of maternal near-miss (MNM) morbidity in a tertiary hospital setting in Turkey. MATERIAL AND METHODS: In this retrospective study, we concluded 125 MNM patients who delivered between January 2017 and December 2017 and fulfilled the WHO management-based criteria and severe pre-eclamptic and HELLP patients which is the top three highest mortality rates due to pregnancy. Two maternal death cases were also included. The indicators to monitor the quality of obstetric care using MNM patients and maternal deaths were calculated. Demographic characteristics of the patients, the primary diagnoses causing MNM and maternal deaths, clinical and surgical interventions in MNM patients, shock index (SI) value of the patients with obstetric hemorrhage and maternal death cases were evaluated. RESULTS: The MNM ratio was 5.06 patients per 1000 live births. Maternal mortality (MM) ratio was 8.1 maternal deaths per 100 000 live births. SMOR was 5.14 per 1000 live births. The MI was 1.57%, and the MNM/maternal death ratio was 62.4:1. The SI of MNM patients with obstetric hemorrhage was 1.36 ± 0.43, and the SI of the patient who died due to PPH was 1.74. CONCLUSION: The MNM rates and MM rates in our hospital were higher than high-income countries but were lower than in low- and middle-income countries. Hypertensive disorders and obstetric hemorrhage were the leading conditions related to MNM and MM. However, the MIs for these causes were low, reflecting the good quality of maternal care and well-resourced units. Adopting the MNM concept into the health system and use as an indicator for evaluating maternal health facilities is crucial to prevent MM.

Circulating levels of Elabela in pregnant women complicated with intrauterine growth restriction.

OBJECTIVE: This study aimed to detect Elabela concentrations in the serum of normotensive pregnant women complicated with intrauterine growth restriction (IUGR) and compare them with the uncomplicated healthy pregnancies. MATERIAL AND METHODS: This prospective case-control study was performed from May 1, 2020 to September 30, 2020. Of the 92 pregnant patients included in the study, we enrolled 49 normotensive patients complicated with IUGR as the study group, and 43 normotensive healthy gestational age-matched and body mass index (BMI)-matched patients without IUGR or additional pregnancy complication as the control group. Demographic and clinical characteristics, and maternal serum Elabela concentrations were recorded. RESULTS: Maternal serum Elabela levels were significantly lower in IUGR pregnancies (4.02±3.42 ng/mL) compared to healthy pregnant women (14.01±18.38 ng/mL, p<0.001). There was a positive intermediate correlation between maternal serum Elabela levels and the birth weight (r = 0.308, p = 0.004). CONCLUSION: Maternal circulating levels of Elabela were significantly lower in IUGR pregnancies than in healthy pregnant women. Also, birth weight was positively correlated with maternal serum Elabela levels. We consider that Elabela might be a crucial biomarker of the pathophysiologic process in pregnancies complicated by IUGR.

Prenatal Diagnosis of Double Aortic Arch: Associated Findings and Postnatal Clinical Outcomes.

OBJECTIVES: The aim of this study is to share our experience in the prenatal diagnosis and characteristics of double aortic arc and neonatal consequences. METHODS: We retrospectively analyzed 2153 fetal echocardiography reports between 2014 and 2019 years. Records of 14 fetuses with double aortic arc were examined. Prenatal and postnatal medical records, sonographic images, genetic reports, associated cardiac and extracardiac anomalies, and neonatal clinical results of affected fetuses were reviewed retrospectively. RESULTS: DAA was isolated in 9 of 14 (64.2%) cases, while the other five cases had cardiac or extracardiac accompanying ultrasound findings. Three of cases (21.4%) were associated with other heart pathologies, including ventricular septal defect, double outlet right ventricle, and persistent left superior vena cava. In 10 cases (71.43%), the right aortic arch diameter was dominant. The left aortic arc was dominant in two cases and both arcs were symmetrical in the remaining two cases. 22q11 microdeletion was the only chromosomal abnormality and was detected in two of nine patients who accepted genetic analysis. Intrauterine fetal death occurred in two of the cases. After birth, in 58.3% (7/12) of the live born cases various degrees of symptoms. Surgical repair was performed with the division of the aorta to all symptomatic cases at different times according to severity of the complaints. CONCLUSIONS: Since it can cause severe respiratory distress in the postnatal period and may accompany chromosomal anomalies, it is important to provide antenatal diagnosis of double aortic arc and adequate counseling to the family.

What is the main factor in predicting the morbidity and mortality in patients with gastroschisis: delivery time, delivery mode, closure method, or the type of gastroschisis (simple or complex)?

Background/aim: There are numerous debates in the management of gastroschisis (GS). The current study aimed to evaluate perinatal outcomes and surgical and clinical characteristics among GS patients based on their type of GS, abdominal wall closure method, and delivery timing. Materials and methods: This study was a retrospective analysis of prospectively collected data of 29 fetuses with GS that were prenatally diagnosed, delivered, and managed between June 2015 and December 2019 at the Obstetrics and Pediatric Surgery Clinics of Kanuni Sultan Süleyman Training and Research Hospital. Results: Twenty-three of the patients had simple GS, and six of them had complex GS. The reoperation requirement, number of operations, duration of mechanical ventilation, time to initiate feeding, time to full enteral feeding, total parenteral nutrition (TPN) duration, TPN-associated cholestasis, wound infection, sepsis, and necrotizing enterocolitis were significantly lower in the simple GS group than in the complex GS group. The mean hospital length of stay was 3.5 times longer in the complex GS group (121.50 ± 24.42 days) than in the simple GS group (33.91 ± 4.13 days, p = 0.009). There were no cases of death in the simple GS group. However, two deaths occurred in the complex GS group. Conclusion: This study indicated that simple GS, compared with complex GS, was associated with improved neonatal outcomes. We suggest that the main factor affecting the patients' outcomes is whether the patient is a simple or complex GS rather than the abdominal wall closure method.

Evaluation of BRD4 levels in patients with early-onset preeclampsia.

OBJECTIVE: This study aimed to detect Bromodomain Containing Protein 4 (BRD4) concentrations in the serum of early-onset preeclamptic patients and compare them with the healthy control group. MATERIAL AND METHODS: This prospective case-control study was performed from June 2019 to December 2019. Of the 80 pregnant patients included in the study, we enrolled 40 patients with early-onset preeclampsia as the study group, and 40 normotensive healthy gestational age- and gravidity-matched patients with normal blood pressure without proteinuria as the control group. Demographic characteristics, amount of proteinuria, and serum BRD4 concentrations were recorded. RESULTS: Maternal serum BRD4 concentrations were significantly higher in patients with preeclampsia (39.10 ± 42.14 ng/mL) compared to the participants in the control group (13.64 ± 7.24 ng/mL, p < 0.001). There was a positive intermediate correlation between serum BRD4 levels and the amount of proteinuria (r = 0.447, p = 0.006). CONCLUSION: Maternal serum BRD4 levels were significantly higher in preeclamptic patients compared to healthy pregnant women. Also, the amount of proteinuria was positively correlated with serum BRD4 levels. Although this preliminary study shows increased BRD4 levels in preeclampsia, its utility as a biomarker must be clarified.

Fetal cardiac tumors: prenatal diagnosis, management and prognosis in 18 cases

Objective: To evaluate the long-term follow-up of patients with fetal cardiac tumors (FCTs), and to review the literature regarding advances in diagnosis and management of FCTs in the last decade. Material and Methods: In this retrospective study, pregnant women referred to a single center maternal-fetal medicine unit between 2013 and 2018 for advanced ultrasonography, were reviewed. Pediatric cardiology counseling was offered to women whose fetuses had FCTs. All patients were evaluated according to revised diagnostic criteria for tuberous sclerosis complex (TSC). Medical treatment was administered to patients with FCTs ≥30 mm or if they were symptomatic. Everolimus therapy at a dose of 2x0.25 mg twice a week for three months was started in the postnatal period. Results: Out of the 75,312 patients referred 18 (0.024%) were diagnosed with FCTs. Six were referred with fetal arrhythmias and the others were diagnosed with FCTs during routine follow-up. Ten patients (55%) with FCTs were diagnosed with TSC. All tumors were assessed to be rhabdomyoma. Mean tumor diameter in fetuses with TSC was significantly larger than those without TSC (29.8±14.1 mm versus 9.3±4.8 mm, respectively; p=0.004). All patients (n=2) who received medical therapy had a diagnosis of TSC and multiple FCTs and a reduction in tumor size occurred. Tumor size decreased in eight patients spontaneously during follow-up, but increased in one patient who had multiple locations but no TCS. No change in size was observed in the remaining seven cases. None of the fetuses died during the 1-5 year follow-up period. Conclusion: Rhabdomyoma are usually multiple and associated with TSC. Rhabdomyomas with TSC are larger, but most regress spontaneously or respond well to medical treatment after birth, and have an excellent long-term prognosis.

Perinatal outcomes of intrauterine transfusion for foetal anaemia due to red blood cell alloimmunisation.

The aim of this study was to evaluate the maternal and neonatal outcomes of patients who underwent intrauterine transfusion (IUT) for foetal anaemia due to red blood cell alloimmunisation and to determine the factors that affected the outcomes. All pregnancies that were treated with IUT due to Rh immunisation between January 2015 and June 2018 in the Kanuni Sultan Süleyman Training and Research Hospital, Department of Obstetrics and Gynaecology, were evaluated retrospectively. IUT due to non-Rh alloimmunisation, parvovirus B19 infection, chronic fetomaternal haemorrhage and foetal anaemia due to homozygous alpha-thalassemia were not included in the study. The perinatal and neonatal outcomes of the patients were retrospectively analysed. The gestational age, ultrasonography findings before and after IUT, laboratory results, complications related to IUT, and data on the newborns were recorded. The cases were divided into two groups, those with complication and those without complications, and their perinatal outcomes were compared. A total of 110 IUTs were performed in 42 foetuses. The survival rate after transfusion was 80.95%. Procedure-related complications were found in 12.7% of cases. There were no significant differences between the demographic and clinical characteristics of the patients with and without complications. The survival rate was lower and perinatal mortality was higher in foetuses with hydrops fetalis. IUT is a safe and effective procedure that can be used in the treatment of foetal anaemia in experienced centres. Survival rates can be increased by referring patients to experienced perinatology centres, by improving the IUT technique, and by reducing technique-related complications.Impact statementWhat is already known on this subject? The predominant use of IUT is to treat foetal anaemia due to red blood cell alloimmunisation. Despite the decrease after anti-D immune globulin prophylaxis, Rh immunisation is still a major cause of foetal anaemia. However, foetal survival rates have increased with the use of IUT.What do the results of this study add? The survival rates were increased after the development of a high-resolution ultrasound. Because foetal monitoring can be performed by ultrasonography, cord accidents and overload findings can be detected during transfusion, which allows for early interventions and increases survival rates.What are the implications of these findings for clinical practice and/or further research? The IUT procedure can be used in the treatment of foetal anaemia in experienced centres. After the technique was improved, the complication rates related to the procedure were decreased and foetal survival rates were increased. Further studies on the use of different IUT techniques will extend our findings.

Is the effect of melatonin on vascular endothelial growth factor receptor-2 associated with angiogenesis in the rat ovary?

OBJECTIVES: Vascular endothelial growth factor (VEGF) and its receptors play important roles in angiogenesis. Melatonin plays an important role in gonadal development; thus, its effect on the reproductive system is evident. We investigated the influence of melatonin on the expression of VEGF, vascular endothelial growth factor receptor-1 (VEGFR1) and vascular endothelial growth factor receptor-2 (VEGFR2), as well as on changes in oxidative stress markers and follicle numbers in rat ovaries. METHODS: For this purpose, 45 Wistar rats were separated into the following groups: Group 1, control; Group 2, vehicle; and Group 3, melatonin. Rats in Group 3 were treated with melatonin at 50 mg/kg/day for 30 days. The effects of melatonin on the expression of VEGF, VEGFR1 and VEGFR2 were established by immunohistochemistry analysis. The effects of melatonin on antioxidant enzyme activities were demonstrated by spectrophotometric analysis. RESULTS: Based on immunohistochemistry analysis, VEGFR2 was predominantly localized to theca cells in the ovary. Our data indicate that melatonin treatment can significantly increase VEGF and VEGFR1 expression in the ovary ( p <0.05). Additionally, the number of degenerated follicles significantly decreased with melatonin treatment ( p <0.05). Melatonin administration also led to significant increases in antioxidant enzyme levels in the ovary. CONCLUSION: Melatonin treatment exerts protective effects on follicles against increased lipid peroxidation through modulating tissue antioxidant enzyme levels. These effects may be related to angiogenesis and antioxidant activities.

Is the effect of melatonin on vascular endothelial growth factor receptor-2 associated with angiogenesis in the rat ovary?

OBJECTIVES Vascular endothelial growth factor (VEGF) and its receptors play important roles in angiogenesis. Melatonin plays an important role in gonadal development; thus, its effect on the reproductive system is evident. We investigated the influence of melatonin on the expression of VEGF, vascular endothelial growth factor receptor-1 (VEGFR1) and vascular endothelial growth factor receptor-2 (VEGFR2), as well as on changes in oxidative stress markers and follicle numbers in rat ovaries. METHODS For this purpose, 45 Wistar rats were separated into the following groups: Group 1, control; Group 2, vehicle; and Group 3, melatonin. Rats in Group 3 were treated with melatonin at 50 mg/kg/day for 30 days. The effects of melatonin on the expression of VEGF, VEGFR1 and VEGFR2 were established by immunohistochemistry analysis. The effects of melatonin on antioxidant enzyme activities were demonstrated by spectrophotometric analysis. RESULTS Based on immunohistochemistry analysis, VEGFR2 was predominantly localized to theca cells in the ovary. Our data indicate that melatonin treatment can significantly increase VEGF and VEGFR1 expression in the ovary ( p <0.05). Additionally, the number of degenerated follicles significantly decreased with melatonin treatment ( p <0.05). Melatonin administration also led to significant increases in antioxidant enzyme levels in the ovary. CONCLUSION Melatonin treatment exerts protective effects on follicles against increased lipid peroxidation through modulating tissue antioxidant enzyme levels. These effects may be related to angiogenesis and antioxidant activities.

Effect of Melatonin on the Expression of VEGF-A and on the Degeneration of Follicle Reserve in Rat Ovary.

OBJECTIVE: To analyze the effects of melatonin on vascular endothelial growth factor A (VEGF-A) expression and follicle reserve in rat ovary. MATERIALS AND METHODS: A total of 45 female Wistar rats were used in the present study. Rats were divided into three groups: group 1 (control), group 2 (vehicle), and group 3 (melatonin). Rats in the melatonin group were treated with an intraperitoneal injection of melatonin at a dose of 50 mg/kg/day for 56 days. We investigated VEGF-A expression in rat ovary in all the groups using Western blot and reverse transcription-polymerase chain reaction. Histopathological parameters were evaluated using light microscopy. RESULTS: The number of atretic follicles was significantly lower in the melatonin treatment rats than in the control rats (p<0.05); however, the number of antral follicles was significantly higher in the former (p<0.05). Additionally, we observed a weak immunoblot stain in the melatonin group for VEGF-A protein. Interestingly, melatonin treatment induced a significant decrease in VEGF-A expression in the ovary of group 3 rats (p<0.05), whereas no such difference was observed between group 1 and group 2 rats (p>0.05). CONCLUSION: The present study demonstrates that the protective effect of melatonin on the degeneration of follicles in rat ovary is reduced by decreasing the VEGF-A expression. These results suggest that melatonin is effective against follicular atresia and preserves antral follicles, thus, offering a therapeutic advantage in clinical use.