Transplantation of human placental chorionic plate-derived mesenchymal stem cells for repair of neurological damage in neonatal hypoxic-ischemic encephalopathy

Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.

Epigenetic modifications of placenta in women with gestational diabetes mellitus and their offspring

Gestational diabetes mellitus(GDM)is a pregnancy-related complication characterized by abnormal glucose metabolism in pregnant women and has an important impact on fetal development.As a bridge between the mother and the fetus,the placenta has nutrient transport functions,endocrine functions,etc.,and can regulate placental nutrient transport and fetal growth and development according to maternal metabolic status.Only by means of placental transmission can changes in maternal hyperglycemia affect the fetus.There are many reports on the placental pathophysiological changes associated with GDM,the impacts of GDM on the growth and development of offspring,and the prevalence of GDM in offspring after birth.Placental epigenetic changes in GDM are involved in the programming of fetal development and are involved in the pathogenesis of later chronic diseases.This paper summarizes the effects of changes in placental nutrient transport function and hormone secretion levels due to maternal hyperglycemia and hyperinsulinemia on the development of offspring as well as the participation of changes in placental epigenetic modifications due to maternal hyperglycemia in intrauterine fetal programming to promote a comprehensive understanding of the impacts of placental epigenetic modifications on the development of offspring from patients with GDM.

Association between Placental Malaria and Severe Pre-Eclampsia in Two University Hospitals of Yaounde City

Context: Pre-eclampsia and placental malaria, are two diseases that share pathophysiological similarities, such as placental ischemia, endothelial dysfunction and production of pro-inflammatory cytokines. Objective: The objective of our study was to investigate the association between placental malaria lesions and severe pre-eclampsia. Methodology: We conducted a prospective analytical cross-sectional study in two University Hospitals in the city of Yaounde (Yaounde Central Hospital and the Gynaecological Obstetrics and Paediatrics Hospital), and in the laboratory of the Centre Pasteur in Yaounde over an eight-month period (1st January 2021 – 1st September 2021). All patients with pre-eclampsia diagnosed according to the criteria of the International Society for the Study of Hypertension (ISSHP) and free of chronic metabolic or infectious pathology were included in this study. The patients were divided into two groups: group 1 (mild pre-eclampsia) and group 2: severe pre-eclampsia. Socio-demographic, clinical and histopathological characteristics specific to pre-eclampsia and placental malaria were investigated. Statistical analysis was performed with SPSS 23.0 software, Chi 2 was used to compare categorical variables, Student t-test was used to compare means, and logistic regression was used to assess the association between placental malaria lesions and PES. Results: The mean age of our study population was 29.93 ± 7.36 years versus 28.28 ± 7.18 years in patients with mild and severe pre-eclampsia respectively. Pre-eclampsia placental lesions (accelerated villous maturation, infarction) were significantly greater in patients with severe pre-eclampsia (p Conclusion: Placental malaria lesions were significantly associated with severe pre-eclampsia and increased the risk of developing severe pre-eclampsia placental lesions by a factor of 10.

Advanced glycation end-products change placental barrier function and tight junction in rats with gestational diabetes mellitus via the receptor for advanced glycation end products/nuclear factor-κB pathway

The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.

Accuracy of Trans-Cerebellar Diameter and Placental Thickness in Third Trimesteric Pregnant Women for Calculation of Gestational Age: A Cross Sectional Study

Background: Accurate determination of gestational age has become important for deciding the appropriate time for termination of the pregnancy as well as to monitor the fetal growth during the entire period of pregnancy. Objective: The aim of the study was to assess whether the trans-cerebellar diameter, placental thickness or combining both of them is more accurate for assessment of gestational age in the 3rd trimester of pregnancy. Patients and Methods: This is a cross sectional study conducted at outpatient Clinic and Obstetric ward, Ain Shams University Maternity Hospital, over a period of six months from March 2019 to September 2019. One hundred pregnant women were recruited according to inclusion criteria either from outpatient clinic or were admitted in obstetric ward Ain Shams Maternity Hospital to find out the most accurate fetal biometric measurement in the third trimester either trans-cerebellar diameter placental thickness or both compared to reliable LMP (last menstrual period) dates confirmed by crown rump length (CRL) in the first trimester. Results: Trans-cerebellar diameter mean ± SD was 46.0 ± 3.5 with range 38.2 - 51.7. The mean of placental thickness was 39.6 ± 7.1 with range 22.8 - 54.3. Placental thickness had highest determination (0.813) for last menstrual period followed by trans-cerebellar diameter (0.802). Combining trans-cerebellar diameter and placental thickness increased determination (0.902) for last menstrual period. Conclusion: Combined use of trans-cerebellar diameter and placental thickness in the third trimester of pregnancy is a reliable indicator for gestational age in women whose last menstrual period is unreliable or unknown, but placental thickness had higher accuracy than trans-cerebellar diameter.

Association between Placenta Malaria Parasites and Preeclampsia/Eclampsia among Parturient Mothers in Alex Ekwueme Federal University Teaching Hospital Abakaliki

In tropical countries, malaria and preeclampsia/eclampsia are common diseases of pregnancy;and placenta have been implicated in the pathophysiology of both disease processes. The two diseases have pathophysiologic similarities in the placenta such as placenta ischaemia, endothelial dysfunction and production of pro-inflammatory cytokine. Yet, there is paucity of studies on the association of these two disease processes. Determining the association between the two disease processes may help to unravel the pathogenesis of preeclampsia and also help in its prevention and patient management. Objective: Determined the association between placenta malaria parasitemia and preeclampsia/eclampsia among parturients at Alex Ekwueme Federal University Teaching Hospital Abakaliki. Materials and Methods: This was a case control study that was conducted in the Labour wards of department of Obstetrics and Gynaecology, Alex Ekwueme Federal University Teaching Hospital Abakaliki (AEFUTHA) and Mile 4 Missionary Hospital Abakaliki, a comprehensive health care centre in Abakaliki, Ebonyi state. It was conducted over a period of 6 months between 1st October 2021 and 31st March, 2022. The cases in this study were parturients that developed preeclampsia/eclampsia in the course of pregnancy, while the controls were parturient without preeclampsia/eclampsia. Interviewer-administered questionnaires were used to collect data on socio-demographic characteristics, obstetrics and medical histories. Histological examinations were conducted to isolate plasmodium falciparum parasites from placenta samples obtained from the maternal surface of the placenta. The data was processed using Epi Info software. Categorical variables were analyzed using Mc Nemar X2 test, with a p-value of 0.05 considered statistically significant. Logistic regression models were used to estimate the odds ratios (OR) and 95% CI of the association between placenta malaria parasites and preeclampsia/eclampsia was conducted. Relative risk with 95% CI was used to determine both fetal and maternal outcomes. Results: The prevalence of preeclampsia during the study period was 2.9%. Placenta malaria was positive in twenty one (21) of the 67 cases of preeclampsia/eclampsia analyzed, giving a prevalence of 31.3% and in eleven (11) out of 68 controls (normotensive) patients analyzed, giving a prevalence of 16.2%. The presence of placenta malaria significantly increased the odds of developing preeclampsia/eclampsia among parturients (OR = 2.4, 95% CI = 1.0 - 5.4, P value = 0.04). Presence of placenta malaria in mothers with preeclampsia/eclampsia was associated with adverse pregnancy outcomes such as cerebrovascular accident (RR = 19.2, 95% CI = 1.1 - 341.7, P value = 0.04), DIC (RR = 10.9, 95% CI = 1.4 - 88.0, P value = 0.02), abruptio placenta (RR = 2.4, 95% CI = 1.2 - 4.8, P value = 0.01), pulmonary edema (RR = 2.7, 95% CI = 1.1 - 25.9, P value = 0.03), IUGR (RR = 2.1, 95% CI = 1.1 - 4.5, P value = 0.03) and IUFD (RR = 3.8, 95% CI = 1.3 - 11.7, P value = 0.02). Presence of placenta malaria also increased the risk of NICU admission (RR = 2.6, 95% CI = 1.1 - 6.0, P value = 0.03), Low 1st minute APGAR score (RR = 2.7, 95% CI = 1.2 - 6.1, P value = 0.02) and Low 5th minute APGAR score (RR = 3.0, 95% CI = 1.0 - 8.6, P value = 0.04) among neonates delivered by mothers with preeclampsia/eclampsia. However, presence of placenta malaria did not significantly increase maternal and perinatal mortalities. Conclusion: There is a higher prevalence of placenta malaria among mothers with preeclampsia/eclampsia when compared with normotensive controls and this was associated with increased risk of certain maternal and perinatal morbidities. Placental malaria was not associated with increased risk of either maternal or perinatal mortality.

Unpredictable Placental Abruption: Case Series

Background: The diagnosis of placental abruption is primarily clinical, but findings from imaging, laboratory, and postpartum pathologic studies can be used to support the clinical diagnosis. In patients with classic symptoms, fetal heart rate abnormalities, intrauterine fetal demise, and/or disseminated intravascular coagulation strongly support the clinical diagnosis and indicate extensive placental separation. In a few cases, placental separation has not been recognized and was only identified upon cesarean section as an incidental finding. Objectives: To describe the clinical presentations and pregnancy outcomes of placental abruption cases that are not diagnosed before cesarean delivery, termed “unpredictable placental abruption” and also cases diagnosed before cesarean delivery, termed “predictable placental abruption”. Methods: A retrospective analysis of 100 cases of placental abruption was identified by cesarean delivery at Tu Du hospital from September 2018 to May 2019. Clinical variables were compared between the unpredictable and predictable groups. The unpredictable group consists of cases that are not diagnosed before cesarean delivery, while the predictable cases were identified placental separation before cesarean delivery. The maternal and fetal outcomes were also studied. Results: In 100 cases of placental, abruption by gross clinical examination of the placenta at the time operation revealed that, 33% were unpredictable. Placental abruption attributed to maternal complications included one case of total hysterectomy (1%) with no cases of disseminated intravascular coagulation (DIC), shock or maternal death;specifically, this case of total hysterectomy appeared with predictable one. There were two cases of stillbirths. Among the 98 live neonates, 15 cases (14.7%) experienced severe birth asphyxia resulting in eight neonatal deaths;two of which were caused by heart disease and necrotizing enterocolitis. Sixty-three neonates were delivered prematurely (61.74%), with mean gestational age of 34.64 ± 3.32 weeks. Among the 33 unpredictable cases, there were no stillbirths but 60.6% and 12.1% experienced moderate and severe asphyxia, respectively. All unpredictable cases had obvious indications of cesarean section but the basic symptoms and signs of acute placental abruption included the onset of preterm labor, unspecified intrapartum hemorrhage, hypertonic uterine contractions and fetal distress for emergency caesarian section;however there were also cases where there were no symptoms and signs. Conclusions: Unpredictable placental abruption cases—not suspected of having abruption, termed—“concealed” or “chronic” placental abruption, may have variable clinical manifestations and better pregnancy outcomes.

Subsequent placenta accreta after previous mifepristone-induced abortion: A case report

BACKGROUND Mifepristone-induced abortion(MIA)has been used worldwide to terminate pregnancies.However,the association between placenta accrete(PA)and MIA has seldom been reported.CASE SUMMARY A 26-year-old pregnant woman presented with painless vaginal bleeding at 35 wk of gestation.She had a medical abortion(mifepristone followed by misoprostol)1 year ago at the sixth week of gestation.Her personal history for previous surgery was negative.Abdominal ultrasonography showed a normal foetus with complete placenta previa.The foetal membrane ruptured with massive vaginal bleeding and severe abdominal pain.An emergency Caesarean section was performed,and the newborn was delivered.The placenta failed to expel and manual extraction was carried out.A large defect was noted in the uterine fundus and repair of the uterine rupture was conducted immediately.The postoperative pathology report showed placenta accreta.CONCLUSION The evidence suggests a possible etiologic role of MIA in PA,as the incidence of PA after MIA is much higher than general population.Millions of pregnancies are complicated by PA each year,some of which result in fatality.To prevent subsequent placental complications after MIA,hormonal supplementation might be a promising therapeutic options.However,further studies are needed to identify the high-risk factors and to confirm the effectiveness of estrogen supplement therapy.

Detecting Accuracy of Three Dimensional Power Doppler (3DPD) Vascular Indices for Prenatal Diagnosis of Morbidly Adherent Placenta in Patients with Placenta Previa

Objective:?The study’s objective was to assess the accuracy of using prenatal 3-dimensional power Doppler analysis of vascular placental indices to accurately diagnose morbidly adherent placenta objectively. Background:?Traditionally, 2D ultrasound was used for the diagnosis of a suspected morbidly adherent placenta (MAP) previa. More objective techniques like 3D power Doppler haven’t been well studied. Study Design:?A prospective cohort study?is?designed for women with gestational age between 28 and?32 weeks with suspected placenta previa. Patients were examined by 2D ultrasound which was used in management decisions.?3D Power Doppler’s VI, FI and VFI were measured during the same examination after manual tracing of placenta;data were blinded to obstetricians. Histopathology was performed to confirm MAP. Results: Our results showed that the 3D power Doppler VI ≥ 16 predicted the diagnosis of MAP with 100% sensitivity, 100% specificity which is better than those of 2D ultrasound. While VI > 33.1 measured by 3D Doppler predicted severe MAP with a sensitivity of 73.9% and specificity of 86.4%, which was superior to 2D ultrasound. Conclusion:?In patients with placenta previa, the 3D Doppler’s vascular index accurately predicts MAP. Furthermore, vascular and vascular flow indices of 3D Doppler were more predictive of severe cases of MAP compared to 2D ultrasound.

Accessory Placental Structures—A Review

Many studies have reported on the different types of placenta in different species, but accessory or paraplacental structures are mentioned only in species that have such a nutrient-exchanging mechanism. Hystricomorph rodents possess a subplacenta, swine and equines have the placental areola, equines have the chorionic girdle, and carnivores have hemophagous organs that are equivalent to the placental hematoma in ruminants. These accessory structures are specialized tissues for specific nutrient exchanges in different species, and they are adaptive modifications exhibited by domestic and wild species to remedy the nutritional deficiencies that are related to permeability of the main placenta to important nutrients for the growth and development of the fetus during the gestation.

Development of a surgical procedure for removal of a placentome from a pregnant ewe during gestation

Background: In recent decades, there has been a growing interest in the impact of insults during pregnancy on postnatal health and disease. It is known that changes in placental development can impact fetal growth and subsequent susceptibility to adult onset diseases;however, a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation without compromising the pregnancy has not been described. The ewe is an established biomedical model for the study of fetal development. Due to its cotyledonary placental type, the sheep has potential for surgical removal of materno-fetal exchange tissues, i.e., placentomes. A novel surgical procedure was developed in well-fed control ewes to excise a single placentome at mid-gestation.Results: A follow-up study was performed in a cohort of nutrient-restricted ewes to investigate rapid placental changes in response to undernutrition. The surgery averaged 19 min, and there were no viability differences between control and sham ewes. Nutrient restricted fetuses were smaller than controls(4.7 ± 0.1 kg vs. 5.6 ± 0.2 kg;P < 0.05), with greater dam weight loss(-32.4 ± 1.3 kg vs. 14.2 ± 2.2 kg;P < 0.01), and smaller placentomes at necropsy(5.7 ± 0.3 g vs. 7.2 ± 0.9 g;P < 0.05). Weight of sampled placentomes and placentome numbers did not differ.Conclusions: With this technique, gestational studies in the sheep model will provide insight into the onset and complexity of changes in gene expression in placentomes resulting from undernutrition(as described in our study),overnutrition, alcohol or substance abuse, and environmental or disease factors of relevance and concern regarding the reproductive health and developmental origins of health and disease in humans and in animals.

Placental Vascularization and Apoptosis in Rats Orally Exposed to Low Doses of Bisphenol A

Aim: Exposure to the ubiquitous endocrine disrupter Bisphenol A (BPA) has been associated, in pregnancy, with low birth weight. The aim of our study is the identification of the damage caused by Bisphenol A on placental tissue through the evaluation of its effects on micro-vessel density and apoptosis. Methods: After fertilization, we exposed 3 female rats to oral BPA, by means of a free access to a beverage solution containing 100 μg/L of BPA. Three female rats were used as controls. Placentas underwent histological examination and immunohistochemistry for von Willebr and factor (F-VIII) and caspase-9. Results: Sixty-seven fetuses have been produced, 30 from control rats and 37 from exposed rats. Exposed fetuses showed a lower longitudinal/transverse diameter ratio than controls (2.57 ± 0.29 vs. 2.78 ± 0.38, p < 0.05). Also, exposed fetuses showed a significant reduction in the number of placental vessels per field (124.86 ± 19.15 vs. 143.54 ± 22.09, p < 0.05). On the other hand, apoptosis is not increased by exposure, as shown by caspase-9 levels. Conclusion: Exposure to BPA during pregnancy may affect placental vascularization, and this phenomenon may explain the lower birth weight reported. However, our results do not show the increase in apoptosis observed in vitro.

Role of Placenta Parameters in Predicting Significant Feto-Maternal Haemorrhage

Purpose: Feto-maternal haemorrhage (FMH) is a complication of pregnancy and large FMH may lead to life-threatening anaemia in the fetus or newborn. In addition, exposure of Rhesus (Rh) D negative women to small amounts of fetal Rh D positive red cells during pregnancy or delivery may result in sensitization with its attendant problems of isoimmunisation. In most cases, the cause of FMH IS unknown. Through this study, we sought to determine if placental weight & diameter have any direct relationship with incidence and severity of FMH.Methods: This was a prospective study of parturients for presence of fetal red cells in the maternal blood circulation. The prepared slide was processed as in the acid elution test described by Kleihauer-Betke. The FMH was calculated using Mollison formula. Baseline data included maternal biodata, blood group, Rh D factor, placenta weight and diameter. Data generated were analysed with Frequency tables, cross-tabulations and Odd ratio and confidence intervals as appropriate.Results: Three hundred parturients were studied. However, only two hundred and ninety-five parturients were analysed, with five excluded due to lysed blood samples. A total of 52 parturients (17.63%) had demonstrable FMH, of which 8 (2.71%) were large FMH (>15 ml foetal cells). Both the placenta weight (P g, in contrast to 4.17% (4/96) in the group with weight of placenta below or equal to 500 g. All the 8 parturients with large FMH had placenta weights greater than 500 g. Placenta diameters were greater than 22 cm in 41/197 (20.81%) who had demonstrable FMH, compared with 11/98 (11.23%) whose diameter was less than 22 cm. Conclusion:Both the placenta weight and diameter are significant predictors of FMH in parturients. However, placenta diameter appears to be a minor predictor. These are factors that can be assessed antenatally by ultrasonography and in conjunction with other known obstetric factors, may possibly be considered in risk-based scoring system for predicting feto-maternal haemorrhage.

Distinct Placenta Increta and Percreta in the Setting of Dichorionic Diamniotic Twin Gestation: A Unique Histological Finding

Multiple gestations have been reported as a risk factor for placenta accreta spectrum (PAS) but the evidence is limited. Previous reports showed that PAS degrees (creta, increta, percreta) were similar in multiple gestation placentas. To our knowledge, there have been no reports of PAS in dichorionic placentas with different degrees of invasion. Here, we report dichorionic diamniotic placentas with two different degrees of invasion, one increta and another percreta.

Placenta Increta in Week 10 of Pregnancy with Consecutive Hysterectomy: A Case Report

Purpose: Placenta increta in early pregnancy is rare and has been documented in only few cases and is a complication of pregnancy that can be life threatening for both mother and fetus. Thus early diagnosis of this problem is very important. This problem is a result of inadequate development of the decidua. Case Presentation: A 26 years old woman (gravid 3, para 2) with history of cesarean section for two times, referred to our center with vaginal bleeding with gestational age of 10 weeks and pelvic ultrasonography showed molar or missed pregnancy. The patient was operated by suction curettage. It’s noteworthy to mention that during the procedure sever vaginal bleeding occurred so that total abdominal hysterectomy was done. Histological examination identified placenta increta. Conclusion: In our community, the diagnosis and treatment of placenta accrete in early pregnancy are so crucial and must be taken seriously with considering the fact that the number of repeated cesarean section is high and placenta accreta is one of the most important complication of this method.

Histopathological Aspects of Placental Lesions in Mild and Severe Pre-Eclampsia in a Population of Cameroonian Women

Background: Pre-eclampsia (PE) frequently leads to adverse maternal and foetal outcomes in our setting. The pathophysiology is strongly linked to placental development. We aimed to study placental lesions associated with PE in a population of Cameroonian women. Methods: We conducted a cross-sectional, analytical study in three university teaching hospitals in Yaounde namely, the Yaounde Central Hospital, the pathology laboratory of the Yaounde University Hospital Centre, and the Yaounde Gynaeco-Obstetric and Paediatric Hospital. The study spanned 8 months from January 1st to September 1st, 2021. Placental analysis was carried out as per standard protocol. The study included 101 parturients with pre-eclampsia. These were divided into two groups, with groups 1 and 2 being made of patients with mild pre-eclampsia (n = 40), and severe pre-eclampsia (n = 61), respectively. Results: The mean ages of the two groups were 29.93 ± 7.36 versus 28.28 ± 7.18 (p = 0.267) for patients with mild and severe pre-eclampsia respectively. Low socioeconomic status was the most frequently identified risk factor in both groups (59%). Patients’ history revealed that the women with severe pre-eclampsia tended to have poor pregnancy follow-up compared to those with mild pre-eclampsia (p < 0.05). Also, the placentas of patients with severe pre-eclampsia weighed significantly less than those of patients with mild pre-eclampsia (454.4 ± 122 vs. 511.7 ± 125;p < 0.05). Pre-eclampsia-related lesions were significantly greater in patients with severe disease (p Conclusion: PE-related placental lesions in our context are multiple and diverse especially in severe disease, and these arise as a result of defective maternal vascular perfusion.

Consequences of gestational and pregestational diabetes on placental function and birth weight

Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring's later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimentalmodels, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proin ammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.

Effect of hypoxia on expression of placental trophoblast cells SATB1 and β-catenin and its correlation with the pathogenesis of preeclampsia

Objective: To study the effect of hypoxia on the expression of placental trophoblast cells SATB1 and β-catenin and its correlation with the pathogenesis of preeclampsia. Methods: Trophoblastic cell lines HRT8/SVneo were cultured, SATB1 and β-catenin expression and cell biological behavior were determined after hypoxia reoxygenation treatment; cell biological behavior and the expression of related genes were determined after the transfection of SATB1 and β-catenin siR NA; preeclampsia placenta and normal placenta tissues were collected and the expression of SATB1 and β-catenin were determined. Results: OD value, cell migration rate, m RNA contents of SATB1 and β-catenin of H/R group were significantly lower than those of Nor group, cell apoptosis rate was higher than that of Nor group and the number of invasive cells was less than that of Nor group; OD value and bcl-2 mRNA content of SATB1-siRNA group were lower than those of NC group; cell apoptosis rate as well as Bax, Caspase-3, caspase-6 and caspase-9 mRNA contents were higher than those of NC group; cell migration rate as well as CTSB, CTSD, MMP2 and MMP9 mRNA contents of β-catenin-siRNA group were lower than those of NC group; the number of invasive cells was less than that of NC group; the expression levels of SATB1 and β-catenin in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue. Conclusions: Hypoxia can inhibit the expression of SATB1 and β-catenin in the pathogenesis of preeclampsia, which can affect the proliferation, apoptosis, migration and invasion of cells.

Altered expression of mitochondrial related genes in the native Tibetan placents by mitochondrial cDNA array analysis

Objective： To explore the mechanism of native Tibetan fetuses adaptation to hypoxia, we tried to find the different expression genes about mitochondrial function in the native Tibetan placents. Methods： In this study, the placents of native Tibetan and the high-altitude Hart （ha-Hart） were collected. After the total RNA extraction, the finally synthesized cDNAs were hybridized to mitochondrial array to find the altered expression genes between them. Then, the cytochrome c oxidase 17 （Coxl7）, dynactin 2 （DCTN2, also known as p50）, and vascular endothelial growth factor receptor （VEGFR, also known as KDR） were chosen from the altered expression genes to further verify the array results using the SYBR Green real-time PCR. Because the altered expression genes （such as Cybb and Cox 17） in the array results related to the activities of COXI and COXIV, the placental mitochondria activities of COXI and COXIV were measured to find their changes in the hypoxia. Results： By a standard of≥1.5 or ≤0.67, there were 24 different expressed genes between the native Tibetan and the ha-Han placents, including 3 up-regulated genes and 21 down-regulated genes. These genes were related to energy metabolism, signal transduction, cell proliferation, electron transport, cell adhesion, nucleotide-excision repair. The array results of Cox17, DCTN2 and KDR were further verified by the real-time RT-PCR. Through the mitochondria respiration measurements, the activity of COXI in the native Tibetan placents were higher than that of ha-Han, there was no difference in COXIV activity between them. Conclusion： The altered mitochondrial related genes in the native Tibetan placents may have a role in the high altitude adaptation for fetuses through changing the activity of mitochondrial COX.

Effect of Bushen Yiqi Huoxue Recipe on Placental Vasculature in Pregnant Rats with Fetal Growth Restriction Induced by Passive Smoking

Interactions of vascular endothelial growth factor （VEGF） with receptors VEGFR1/Fltl and VEGFR2/Flk1, and those of angiopoietins （Ang-1, Ang-2） with receptor Tie2 play important roles in placental angiogenesis. This study investigated vascular morphology and expression of these angiogenic factors in rat placenta on the day 15, 18, 21 of gestation （D 15, D 18 and D21）. The rats were randomly assigned into 3 groups： normal group, model group [fetal growth restriction （FGR） model], and Bushen Tqi Huoxue （BYHR） recipe treatment group （BYHR group, the pregnant rats with FGR were treated with BYHR recipe）. Morphological analysis indicated that during initial villous formation, fetal nucle- ated erythrocytes （FNEs） appeared in maternal blood sinus （MBS）. Subsequently, FNEs were sur- rounded by endothelial cells to form fetal capillary （FC） and then by trophoblast cells to form villi. As pregnancy proceeded, FC density increased progressively with increasing endothelial identification staining （EIS） in normal and BYHR groups. Whereas, villous formation was suppressed, normal in- crease in FC density was impaired and EIS was weakened in model group. Quantitative PCR analysis showed that VEGF and Flkl mRNA increased over gestation in all groups, indicating that VEGF might play a pivotal role in FC growth during late gestation. VEGF mRNA was increased on D15, while de- creased on D21 in model group as compared with normal group and BYHR group. Immunohistochemi- cally, Ang-2 protein was highly expressed in FNEs, gradually disappeared as villi matured, and decreased over gestation in all groups, indicating that Ang-2 might play a pivotal role in villous formation, which was further supported by decreased Ang-2 mRNA and protein expression in model group on D 15. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio increased from D15 to D18 in all groups as placenta matured. Ang-1 mRNA, Tie2 mRNA and Ang-1/Ang-2 ratio were decreased on D18 in model group as compared with normal and BYHR groups, indicating delayed maturity of FGR placenta. Alterations in angiogenic factors may result in altered placental vasculature and cause placental insufficiency. BYHR recipe could balance the angiogenic factors to promote the formation and maturation of FGR placental vasculature.