Significance of Physical Exercise in Pregnancy: Comparison of Short and Long Exercise Programs.

BACKGROUND: Several musculoskeletal changes occur in pregnancy, particularly in the abdominal region. The aim of this study was to search and compare the effects of long (LEP) and short exercise programs (SEP) in terms of the satisfaction of the needs of pregnant women. METHODS: This study consisted of 2 groups: LEP (n=16) and SEP (n=16). Muscle thickness measurements determined by ultrasound, the 6 minute walk test, Pregnancy Physical Activity Questionnaire, Visual Analogue Scale, Oswestry Disability Index, and Short Form-36 Quality of Life Questionnaire were the study variables. Evaluations were done at the 16th (baseline), 24th, and 32nd gestational weeks. The LEP consisted of 20 and the SEP consisted of 9 exercises, which were applied for 16 weeks until the 32nd gestational week. RESULTS: Emotional role limitation and pain scores of quality of life, 6 minute walk test, and occupational physical activity were found to be better in the LEP group at the 24th gestational week (p=0.043, p=0.049, p=0.049, p=0.026). At the 32nd gestational week, the 6 minute walk test and occupational physical activity were found to be higher in the LEP group (p=0.006, p=0.017). Additionally, rectus abdominis and bilateral diaphragm muscle thicknesses, "moderate intensity and sports physical activity" and "vitality and emotional well-being" were increased over time with the LEP (p+<+0.05 for all). On the other hand, unilateral diaphragm muscle thickness, sports physical activity level, and vitality were improved with the SEP (p+<+0.05 for all). CONCLUSIONS: The SEP and LEP both have beneficial effects in pregnant women. However, the LEP increases physical activity level, functional capacity, and quality of life more than the SEP during the later stages of pregnancy.

Segmental hair metabolomics analysis in pregnant women with pregnancy complications.

INTRODUCTION: Pregnancy complications, as preeclampsia (PE) and HELLP syndrome, occurring with similar pathophysiological mechanisms, have adverse effects on the health of both mother and fetus during pregnancy and thereafter, they are leading causes of maternal and fetal morbidity and mortality. The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information to be able to assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. OBJECTIVE: The aim of this study was to investigate the hair metabolome profile of pregnant women with PE, HELLP syndrome and healthy women. METHOD: Hair samples of new-borns' mothers (patients and controls) were investigated segmentally relevant to each trimester using a proper sample preparation and gas chromatography-mass spectrometry (GC-MS) to identify robust biomarkers that can be useful for screening, early detection, follow-up and treatment of PE and HELLP syndrome, the etiology of which are still unknown. RESULTS: The results showed a significant change in the metabolome profiles of the patient and control groups regarding the trimesters. A striking decrease was observed in all 100 metabolites investigated in the patient group (p < 0.000). The metabolic pathways associated with significant metabolites have also been investigated, and the most affected pathways were observed to be the urea cycle, glycine, serine, aspartate, methionine and purine metabolism, ammonia cycle, and phosphatidylethanolamine biosynthesis. CONCLUSION: The found metabolites provide us with extensive data on the ability to establish biomarkers for predicting, early detection and monitoring of PE.

Fetal cardiac interventions: First-year experience of a tertiary referral center in Turkey.

AIM: To present the first-year experience of fetal cardiac interventions (FCIs) in a tertiary referral hospital and to evaluate the outcomes. METHODS: This retrospective study consisted of four pregnant women who underwent fetal pulmonary or aortic balloon valvuloplasty between November 2020 and June 2021. The procedures were performed with a percutaneous cardiac puncture under the ultrasonography guidance. Gestational age at intervention, procedural success, complications, and perinatal outcomes were evaluated. Procedural complications defined as fetal bradyarrhythmia requiring treatment, pericardial effusion requiring drainage, balloon rupture, and fetal death. The procedure was considered technically successful if the valve was dilated with a balloon catheter. Ultimately successful procedure was defined as the discharge of infants alive with biventricular circulation. RESULTS: A total of 5 FCIs attempted between 26 + 3 and 28 + 2 gestational weeks. While the procedure was technically successful in 2 cases with pulmonary stenosis, both attempts were unsuccessful in the fetus with pulmonary atresia. Although the procedure was technically successful in the patient with critical aortic stenosis, it ultimately failed. No fetal death occurred in our series and there were no procedure-related significant maternal complications. However, three interventions were complicated by fetal bradycardia and pericardial effusion necessitating treatment, and balloon rupture cropped up in one case. CONCLUSION: FCIs may lead to improving the likelihood of a biventricular outcome for selected fetuses. Careful selection of patients and centralization of experience are essential for obtaining favorable outcomes. Operators should be aware of procedural complications. Improved procedural techniques with a lower complication rate will be achieved through advanced medical technology and special balloon catheters.

Bisphenol derivatives in cord blood and association between thyroid hormones and potential exposure sources.

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT4) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (ß = 0.26; p = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health.

The effect of forced-air warming in the cesarean section on maternal hypothermia, shivering, and thermal comfort: A randomized controlled trial.

This trial was carried out to investigate the effect of forced air warming in various body areas of women on hypothermia during cesarean delivery. The patients in the study groups (n = 76) were assigned to the full-body warming group, upper-extremity warming group, lower-extremity warming group, and control groups. The intervention groups received forced-air warming 30 min before the surgery and continued until 30 min after surgery. The incidence of hypothermia was significantly higher in the control group than in the other groups at the 60th minute of the operation (p < 0.01). The intervention and control groups showed significant differences in the frequency of shivering at the entrance to the PACU (p = 0.001). Thermal comfort scores have significant difference between the control group and all of the intervention groups (p<.001). It is said that the full-body forced-air warming technique prevents hypothermia, shivering, and thermal discomfort in women Cesarean Section (CS).

Fetal Mediastinal Fibrosarcoma. Report of Two Cases.

Introduction: One-third of fetal soft tissue tumors are malignant and include congenital fibrosarcoma (CF). We report two fetal CFs arising in the posterior mediastinum. Case Presentation: In case 1, the CF resulted in a mediastinal shift, extensive infiltration of the tumor around adjacent structures, pulmonary hypoplasia, pleural effusion, and rapid growth. The pregnancy was terminated. Case 2 had multiple intrathoracic masses, thoracic hypoplasia, pleural effusion, and fetal death. Both were diagnosed as fibrosarcoma at fetopsy. Discussion: Although congenital CF tends to be locally aggressive with a low metastatic rate, it tends to grow rapidly and the tumor location can affect fetal survival. In Case 1, the tumor demonstrated locally aggressive behavior whereas multiple distant metastases such as lung, liver, adrenals, and left eye were detected in Case 2. The tumor was directly responsible for intrauterine fetal demise in the second case.

Anxiety, depression and concerns of pregnant women during the COVID-19 pandemic.

PURPOSE: In December 2019, the emerging of a novel coronavirus (COVID-19) has influenced the whole world. The current pandemic also triggers several psychological changes. Uncertainties and changes in health practices may cause anxiety, depression, and concerns on vulnerable populations such as pregnant. This study aims to survey the pregnant women to capture the psychological impact and perceptions during the pandemic. METHODS: A total of 297 pregnant women aged ≥ 18 years were enrolled in May 2020. We evaluated the hard-copy survey included questions about demographic and clinical information of patients, 95% confidence intervals of a COVID-19-related questionnaire in a Likert scale and 14-item Hospital Anxiety and Depression Scale (HADS). RESULTS: A total of 297 pregnant women were included in this study with a mean age of 27.64. Most patients (82.5%) had concerns about infecting their babies during delivery. The fear of infection of the fetus during delivery revealed elderly age and having anxiety as the unique significant risk factors. Mean HADS-A and HADS-D scores were 7.94 (± 4.03) and 7.23 (± 3.84), respectively. Multivariate analysis showed having anxiety was associated with a high HADS-D score and concern about the inability to reach obstetrician, and being in advanced age, having a high HADS-A score, and concern about the inability to reach obstetrician demonstrated significant effects on HADS-D score. CONCLUSION: We conclude that in future pandemics, communications and reassurance of the patients should be prioritized upon their routine ante-natal care to avoid increased levels of anxiety and even depression.

Impact of Increased Nuchal Translucency Values on Pregnancy Outcomes: A Tertiary Center Experience.

OBJECTIVE: We evaluated the association of nuchal translucency (NT) values above 99th percentile with perinatal outcomes. Materials and methods: Singleton pregnancies with NT values above 99th percentile were investigated. Pregnancies were divided into 3 groups: group 1, NT = 2.6-<3.5 mm; group 2, NT = 3.5-4.5 mm; and group 3, NT > 4.5 mm. Demographic features, clinical characteristics, structural/chromosomal anomaly rates and perinatal outcomes were compared. Results: Normal ultrasonographic anatomy was found in 47.5%, 7.7%, and 14.3% of groups 1, 2, and 3, respectively (p = 0.006). Group 3 had the lowest normal karyotype rate (44.6%) (p = 0.005). Higher frequencies for both miscarriage and pregnancy termination were observed in group 3 compared to group 1 (8.9% vs. 4.9% and 66.1% vs. 32.7%, respectively) (p = 0.02). The lowest rate of normal postnatal anatomic findings was found in group 3 (10.7%) (p = 0.01). Conclusion: NT values above 99th percentile for gestational age seem to be associated with increased rates of chromosomal/structural abnormalities and adverse perinatal outcomes.

SUL-109 Protects Hematopoietic Stem Cells from Apoptosis Induced by Short-Term Hypothermic Preservation and Maintains Their Engraftment Potential.

The newly developed 6-hydroxychromanol derivate SUL-109 was shown to provide protection during hypothermic storage of several cell lines, but has not been evaluated in hematopoietic stem cells (HSCs). Hypothermic preservation of HSCs would be preferred over short-term cryopreservation to prevent cell loss during freezing/thawing and would be particularly useful for short-term storage, such as during conditioning of patients or transport of HSC transplants. Here we cultured human CD34+ umbilical cord blood (UCB) cells and lineage-depleted (Lin-) Balb/c bone marrow (BM) cells for up to 7 days in serum-free HSC expansion medium with hematopoietic growth factors. SUL-109-containing cultures were stored at 4°C for 3 to 14 days. The UCB cells were tested for viability, cell cycle, and reactive oxygen species (ROS). DMSO-cryopreserved Lin- BM cells or Lin- BM cells maintained for 14 days at 4°C were transplanted into RAG2-/- Balb/c mice and engraftment was followed for 6 months. The addition of SUL-109 during the hypothermic storage of expanded CD34+ UCB cells provided a significant improvement in cell survival of the immature CD34+/CD38- fraction after 7 days of hypothermic storage through scavenging of hypothermia-induced ROS and was able to preserve the multilineage capacity of human CD34+ UCB cells for up to 14 days of cold storage. In addition, SUL-109 protected murine BM Lin- cells from 14 days of hypothermic preservation and maintained their engraftment potential after transplantation in immune-deficient RAG2-/- mice. Our data indicate that SUL-109 is a promising novel chemical for use as a protective agent during cold storage of human and murine HSCs to prevent hypothermia-induced apoptosis and promote cell viability.

Retrospective analysis of indications for termination of pregnancy.

This is a retrospective study of 139 termination of pregnancies (TOPs) between November 2015 and November 2017 to demonstrate the indications. We have shown that 60.4%, 34.5% and 5% of the terminations were performed because of genetic disorders, foetal or obstetrical problems, and maternal causes, respectively. Congenital abnormalities (43.8%), anhydramniosis (17.2%) and chromosomal abnormalities (15.1%) were the most frequent causes of the TOPs. The central nervous system seemed to be the most frequent indicator found in our study. The critical finding is the presence of nine (6.4%) terminations because of foetal reasons beyond the 24th gestational week. A vaginal termination occurred in 91.4% of cases, whereas a hysterotomy was performed in 8.6% of the cases. Previous uterine surgery was the most significant risk factor for a hysterotomy. Knowing the foetal indications is essential to know the aetiological and medico-legal backgrounds of the TOPs for better planning and medical counselling. Impact statement What is already known on this subject? Congenital anomalies are most common cause of termination of wanted pregnancies. Terminations beyond 24 weeks are also evaluated as unethical and create an ethical concern. The legal limitations differ between countries in terms of the legal limit in pregnancy for terminations. What do the results of this study add? We have demonstrated the congenital anomalies are the most common reason for pregnancy terminations after excluding fetal demise and unwanted pregnancies. We also showed that congenital anomalies and chromosomal abnormalities are most common indications for terminations of pregnancies beyond 24 weeks. The legal arrangements related to the termination of pregnancies in Turkey are described. Prior uterine surgery is a significant risk factor for hysterotomies in the termination of pregnancies. What are the implications of these findings for clinical practice and/or further research? It is critical to know the aetiological background of termination of pregnancies for better planning and consultation.

Gestational Outcomes of Pregnancies with Prenatally Detected Gastroschisis and Omphalocele.

Objective: To evaluate and compare the outcomes of pregnancies with prenatally detected gastroschisis and omphalocele. Materials and Methods: We retrospectively evaluated prenatally detected gastroschisis and omphalocele cases. Cases were compared in terms of maternal demographic and clinical characteristics as well as pregnancy and neonatal outcomes. Results: This study consisted of 17 gastroschisis and 30 omphalocele cases. Only one case with gastroschisis was terminated due to additional severe limb deformities. Seventeen out of 30 cases of omphalocele were terminated for various reasons (56.7%). All patients with gastroschisis had surgical repair, while 8 out of 13 omphalocele cases had surgery. One patient with an omphalocele died after surgery due to sepsis. Six cases of gastroschisis also died in the neonatal period due to various reasons (6/16, 37.5%). Conclusion: Additional genetic disorders are more frequent in those with omphalocele cases, and they are more frequently terminated during gestation that the gastroschisis fetuses.

Clinical analyses of 383 cases with maternal cardiac diseases.

AIM: To evaluate the pregnancy outcomes of women with heart disease. MATERIALS AND METHODS: In this retrospective study, 383 pregnant women with cardiac diseases were examined. The cases were classified according to the World Health Organization (WHO) classification. The distribution of the cases according to class, congenital heart diseases, mean birthweight, mean gestational week at delivery, type of delivery [cesarean section (CS) or vaginal delivery], and cardivascular events (during pregnancy and puerperium) were evaluated. RESULTS: Of the 383 patients, 25 were in Class I; 39, Class II; 255, Class II or III; 31, Class III; and 33, Class IV cardiac diseases. The neonatal birth weights were significantly lower in Class III than in Classes II, and II or III. The preterm delivery rate was higher in Class III than in the other classes. Delivery was performed by CS due to cardiac indications in the high-risk classes, however, only obstetric indications were considered in the low-risk classes. Only one case of maternal death occurred during the postpartum period, in a patient with Eisenmenger's syndrome. DISCUSSION: Cardiovascular diseases are an important cause of mortality and morbidity in pregnancy. The adverse impact of cardiovascular disorders on pregnancy outcomes should be the main concern during the management of these women.

Effect of micronized progesterone on fetal-placental volume in first-trimester threatened abortion.

PURPOSE: To compare the effect of oral micronized progesterone (OMP) on the first-trimester fetal and placental volumes using three-dimensional ultrasonography and extended imaging virtual organ computer-aided analysis (XI VOCAL) method in threatened abortion. METHODS: This randomized controlled trial enrolled women with threatened abortion and a singleton pregnancy from 6-8 6/7 weeks of gestation. A total of 60 women with threatened abortion were randomly assigned to one of two groups: OMP (400 mg/day) (n = 30) and control groups (n = 30). The XI VOCAL method was used for all volume measurements using three-dimensional ultrasonography. All patients were evaluated for fetal, amniotic, and placental volumes during the initial diagnosis and after 4 weeks. RESULTS: After treatment, placental volume difference was significantly higher in the OMP group (336%, 67-1,077) than in the control group (141%, 29-900) (p = 0.007). The mean differences in gestational sac, amniotic sac, and embryonic volumes between the OMP and control groups were not statistically significant. CONCLUSIONS: Hormonal support with OMP is associated with increased placental volume in first-trimester threatened abortion when compared with the control group. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:14-19, 2017.

Fibroids During Pregnancy: Effects on Pregnancy and Neonatal Outcomes.

OBJECTIVE: To determine the effects of fibroids on pregnancy and neonatal parameters. STUDY DESIGN: A total of 12,855 consecutive pregnant women admitted to a tertiary care university hospital between January 2002 and December 2009 were retrospectively reviewed. Of those, 267 patients with fibroids and 267 age- and parity-matched controls were included. The Clavien-Dindo classification was used to grade postoperative complications. RESULTS: Mean gestational age at delivery (p<0.001) and mean neonatal birthweight (p=0.034) were significantly different between the 2 groups. We recorded a higher rate of pain-related hospitalization in the large fibroid group (38.2% and 7.8%, p <0.001). Myomectomy was performed in 124 of 267 patients during cesarean section (C/S). The myomectomy group was associated with lower postoperative hemoglobin levels (p=0.01) and higher need for transfusion (p=0.009). When postpartum hemoglobin levels of the control group and fibroid group without myomectomy were compared, hemoglobin levels were higher in favor of the control group (p = 0.009). CONCLUSION: Beyond lower gestational age and mean birthweight, perinatal complications did not increase with fibroids during pregnancy. Performing myomectomy increases the need for transfusion (Grade 2) without an increase in the risk of hysterectomy (Grade 3) and other life-threatening complications (Grade 4-5). Leaving fibroids in situ during C/S did not prevent a fall in post-partum hemoglobin levels.

Isolation, characterisation and comparative analysis of human umbilical cord vein perivascular cells and cord blood mesenchymal stem cells.

Perivascular cells are known to be ancestors of mesenchymal stem cells (MSCs) and can be obtained from heart, skin, bone marrow, eye, placenta and umbilical cord (UC). However detailed characterization of perivascular cells around the human UC vein and comparative analysis of them with MSCs haven't been done yet. In this study, our aim is to isolate perivascular cells from human UC vein and characterize them versus UC blood MSCs (UCB-MSCs). For this purpose, perivascular cells around the UC vein were isolated enzymatically and then purified with magnetic activated cell sorting (MACS) method using CD146 Microbead Kit respectively. MSCs were isolated from UCB by Ficoll density gradient solution. Perivascular cells and UCB-MSCs were characterized by osteogenic and adipogenic differentiation procedures, flow cytometric analysis [CD146, CD105, CD31, CD34, CD45 and alpha-smooth muscle actin (α-SMA)], and immunofluorescent staining (MAP1B and Tenascin C). Alizarin red and Oil red O staining results showed that perivascular cells and MSCs had osteogenic and adipogenic differentiation capacity. However, osteogenic differentiation capacity of perivascular cells were found to be less than UCB-MSCs. According to flow cytometric analysis, CD146 expression of perivascular cells were appeared to be 4.8-fold higher than UCB-MSCs. Expression of α-SMA, MAP1B and Tenascin-C from perivascular cells was determined by flow cytometry analysis and immunfluorescent staining. The results appear to support the fact that perivascular cells are the ancestors of MSCs in vascular area. They may be used as alternative cells to MSCs in the field of vascular tissue engineering.

Non-immune hydrops fetalis as a diagnostic and survival problems: what do we tell the parents?

OBJECTIVE: Nonimmune hydrops fetalis (NIHF) is one of the most difficult problems related to pregnancy. The aim of this study was to evaluate the etiological analysis as well as the fetal and neonatal outcomes of NIHF. METHODS: We reviewed the prenatal sonographic data and postnatal medical records of pregnant women diagnosed as NIHF in our hospital between January 2001 and May 2013. All cases were categorized using 12 etiological classification groups. Demographic data, diagnostic laboratory parameters, karyotyping results, sonographic and autopsy findings, postnatal final diagnoses, and perinatal mortality rates were also recorded. RESULTS: This study included 147 cases. The mean gestational age at the time of the initial diagnosis was 23.84±6.30 weeks. Cardiovascular causes were the most common (21.7%), followed by structural abnormalities (17.0%), chromosomal abnormalities (6.8%), and skeletal dysplasias (5.4%). Chromosomal abnormalities were detected in 12.8% of these cases. The most common karyotype abnormality was monosomy X. Postmortem autopsy was performed in 50 (34%) cases, and at least one finding was detected in 40 (80%) of these cases. The overall mortality rate was 78.2%. The gestational week at delivery, birth weight, and Apgar score (1st and 5th min) showed a statistically significant difference between exitus and surviving fetuses (P<0.05). CONCLUSION: NIHF can lead to high perinatal morbidity and mortality, yet its etiopathology remains poorly understood. Early diagnosis of NIHF gives parents an opportunity to make an informed choice about the possible complications of a pregnancy.

Myomectomy during cesarean section and adhesion formation as a long-term postoperative complication.

OBJECTIVES: We aimed to evaluate the incidence and features of postoperative adhesion related complications occurring following myolysis or myomectomy performed during cesarean section (C/S). METHODS: This cross-sectional study consists of four groups of patients who underwent C/S: group I; myolysis is performed by electric cauterization for small superficial fibroids less than 2 cm. (n: 21), group II; myomectomy is performed for pedunculated fibroids (n: 18), group III; myomectomy is performed for intramural/subserous fibroids less than 5 cm. (n: 23), group IV control group (n: 19) who did not go through myomectomy Repeat C/S is performed to study subjects within 1-5 years. All cases are evaluated in terms of mild to moderate adhesions between omentum and uterus, mild to moderate adnexial area adhesions, mild to moderate incision area adhesions and surgical difficulty due to severe adhesions. RESULTS: The incidence of adhesions of omentum and uterus (p= 0.278), mild to moderate adnexial area adhesions (p = 0.831), mild to moderate incision area adhesions (p= 0.804) were similar between the intervention groups (group I, II, and III) and the controls (group IV). CONCLUSION: Cesarean myomectomy is a safe procedure and can be performed without significant postoperative adhesion formation.

Ultrasonographic measurement of amniochorionic membrane in asymptomatic pregnant women is not a useful tool for preterm birth prediction.

AIM: The objective of this study was to determine the accuracy of ultrasonographic measurement of amniochorionic membrane thickness (AMT) in the prediction of preterm birth among an asymptomatic pregnant population. METHODS: One hundred and ninety consecutive singleton pregnant women presenting for prenatal care between May 2010 and August 2011 were recruited for the study. AMT of the patients was measured once between 18 and 22 weeks of gestation and then again between 28 and 32 weeks of gestation with transabdominal ultrasound. The results of measurements were recorded and compared with the perinatal outcome related to prematurity. RESULTS: Thirteen of the 190 births were preterm. The mean AMT of the pregnant women who delivered at term were 0.79 ± 0.23 mm in the second trimester and 0.88 ± 0.27 mm in the third trimester. The mean AMT of pregnant women who delivered preterm were 0.77 ± 0.27 mm in the second trimester and 0.91 ± 0.20 mm in the third trimester. There were no statistically significant differences between the second and third trimester AMT of the preterm delivery group and term delivery group (P = 0.542 and P = 0.448, respectively). CONCLUSION: In this study, ultrasonographic measurement of fetal membranes was not found to be a useful marker for prediction of preterm birth. The findings of our study may help in understanding ultrasonographic changes in fetal membranes in normal pregnancies.

Pregnancy outcome of five patients with renal amyloidosis regarding familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disease affecting mainly patients of the Mediterranean basin and its major complication is the development of renal AA amyloidosis. On the other hand pregnancy with amyloidosis is not common; nevertheless, amyloidosis will complicate pregnancies also with the underlying disease and may cause terrible perinatal morbidities and mortalities. We report here the cases of five pregnant women and their pregnancy outcomes, who have been diagnosed with FMF complicated by renal amyloidosis. In the five cases, we observed that increased pregnancy complication such as small for gestational age, intrauterine growth restriction, preeclampsia and preterm birth.

Effects of DDT and DDE on placental cholinergic receptors.

The placental cholinergic system; known as an important factor in intracellular metabolic activities, regulation of placental vascular tone, placental development, and neurotransmission; can be affected by persistent organic pesticides, particularly organochlorine pesticides(OCPs), which can influence various epigenetic regulations and molecular pathways. Although OCPs are legally prohibited, trace amounts of the persistent dichlorodiphenyltrichloroethane(DDT) are still found in the environment, making prenatal exposure inevitable. In this study, the effects of 2,4'-DDT and 4,4'-DDT; and its breakdown product 4,4'-DDE in the environment on placental cholinergic system were evaluated with regards to cholinergic genes. 40 human placentas were screened, where 42,50% (17 samples) were found to be positive for the tested compounds. Average concentrations were 10.44 µg/kg; 15.07 µg/kg and 189,42 µg/kg for 4,4'-DDE; 2,4'-DDT and 4,4'-DDT respectively. RNA-Seq results revealed 2396 differentially expressed genes in positive samples; while an increase in CHRM1,CHRNA1,CHRNG and CHRNA2 genes at 1.28, 1.49, 1.59 and 0.4 fold change were found(p<0028). The increase for CHRM1 was also confirmed in tissue samples with immunohistochemistry. In vitro assays using HTR8/SVneo cells; revealed an increase in mRNA expression of CHRM1, CHRM3 and CHRN1 in DDT and DDE treated groups; which was also confirmed through western blot assays. An increase in the expression of CHRM1,CHRNA1, CHRNG(p<0001) and CHRNA2(p<0,05) were found from the OCPs exposed and non exposed groups.The present study reveals that intrauterine exposure to DDT affects the placental cholinergic system mainly through increased expression of muscarinic receptors. This increase in receptor expression is expected to enhance the sensitivity of the placental cholinergic system to acetylcholine.