Cytotrophoblast Proliferation Research Articles

Gestational trophoblastic disease a contemporary review of diagnostic and pathology. Current challenge and future directions for gynecologists and obstetricians

Gestational trophoblastic disease (GTD) is a heterogenous group of disorders assosiated with abnromal proliferation of trophoblast and their course is characterized by varying degrees of malignancy. WHO classified GTD into three categories: tumor-like lesions, molar pregnancies and gestational trophoblastic neoplasms.HM is characterized by abnormal proliferation of both syncytiotrophoblast and cytotrophoblast, edema of placental villi, with or without the presence of a fetus. Complete and partial moles have been classified as two separate disease entities, and their division depends on the genetic material they contain. The complete mole has a complete set of chromosomes coming only from paternal genome, while the partial mole is triploid and the genetic material transferred comes from the father and the mother. Post-molar gestational trophoblast neoplasia (GTN) is a clinical diagnosis based on the observation of a persistent increase or persistently high hCG concentration after evacuation of the mole, requiring evaluation and treatment. Invasive hydatidiform mole, together with choriocarcinoma and placental tumor, belong to gestational trophoblast neoplasia. Currently, research has shown that short tandem repeat (STR) genotyping is the gold standard for making the correct diagnosis and this test should be performed if possible. GTD diseases originate from both syncytiotrophoblast and cytotrophoblast tissues and as a result of which they produce an extremely sensitive marker -human chorionic gonadotropin. The facts stated above and significant sensitivity to chemotherapy mean that the average cure rate for this disease currently exceeds 90%. Although the main treatment of gestational trophoblast neoplasia involves the use of cytostatics in cases with worse prognosis, i.e. those with a higher risk, surgery turns out to be an invaluable treatment method.

Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

MiR-514a-3p: a novel SHP-2 regulatory miRNA that modulates human cytotrophoblast proliferation

miR-514a-3p: a novel SHP-2 regulatory miRNA that modulates human cytotrophoblast proliferation

To evaluate histopathological changes in placenta of IUGR

The present study entitled “To evaluate Histopathological changes in Placenta of IUGR” was conducted in the Department of Obstetrics and Gynaecology. A total of 400 patients were studied. Out of them 200 were normal patients without IUGR and 200 with IUGR. These patients were evaluated with the help of semistructured proforma consisting of various socio-demographic and clinical variables.Number of LSCS deliveries in IUGR patients (59) is significantly more than control group (33).The number of syncytial knot formation (>10) in IUGR is 169 compared to 153 of control and hence is statistically insignificant. Cytotrophoblastic proliferation (>10) in IUGR (126) is significantly more than (92) in the control group. Number Of area fibrinoid necrosis in villi > 5 in IUGR group is 57 compared to control group (29) (significantly higher) No. of hylinized areas (> 5) in IUGR (101) is significantly higher than in control group (68). Histopathological findings in low power field like syncytial knot formation, cytotrophoblastic cellular proliferation, calcification and hyalinisation of villi are also found as normal aging changes in placenta but it occur early and more frequently per low power field in IUGR group. To conclude, these morphological & histological findings of placenta are the etiological basis for Intra uterine growth restriction.

Bisphenol A-sulfate conjugate disrupts AURKA transcription and cell cycle in BeWo cytotrophoblasts

Bisphenol A (BPA) has been shown to exhibit various toxic effects, including the induction of reproductive disorders. Generally, BPA is converted to conjugated metabolites, leading to bio-inactivation. On the other hand, the toxicity of conjugated metabolites is not fully understood. Notably, the placenta develops the sulfate-sulfatase pathway, which transports and reactivates sulfated steroids. Therefore, we investigated the potential adverse effects of the BPA-sulfate conjugate (BPA-S) on human placenta-derived BeWo cytotrophoblasts. In the present study, high-concentration BPA-S (100 μM) induced significant inhibition of BeWo growth, with effects similar to those seen with unconjugated BPA (100 μM and 100 nM). This growth inhibition was restored by treatment of the cells with an inhibitor of the organic anion-transporting peptides (OATPs) (bromosulphophthalein) or with a sulfatase (STS) inhibitor (STX64). BeWo exhibits expression of the genes encoding OATP1A2 and OATP4A1 as known sulfated steroid transporters and STS, suggesting that BPA-S suppresses cell growth activity via the sulfate-sulfatase pathway. In addition, cell cycle analysis revealed that BPA-S (100 μM) increased the fraction of cytotrophoblasts in the G2/M phases and significantly decreased the accumulation of the transcript encoding Aurora kinase A (AURKA), which is a critical regulator of cellular division. These results suggested that BPA-S triggers cell cycle arrest and inhibits proliferation of BeWo cytotrophoblasts by decreased AURKA, an effect that is mediated by the sulfate-sulfatase pathway. Overall, these findings provide insights into the reactivation of sulfated endocrine-disrupting chemicals and subsequent adverse effects.

MiR-514a-3p: a novel SHP-2 regulatory miRNA that modulates human cytotrophoblast proliferation.

Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP-2), encoded by the PTPN11 gene, forms a central component of multiple signalling pathways and is required for insulin-like growth factor (IGF)-induced placental growth. Altered expression of SHP-2 is associated with aberrant placental and fetal growth indicating that drugs modulating SHP-2 expression may improve adverse pregnancy outcome associated with altered placental growth. We have previously demonstrated that placental PTPN11/SHP-2 expression is controlled by miRNAs. SHP-2 regulatory miRNAs may have therapeutic potential; however, the individual miRNA(s) that regulate SHP-2 expression in the placenta remain to be established. We performed in silico analysis of 3’UTR target prediction databases to identify libraries of Hela cells transfected with individual miRNA mimetics, enriched in potential SHP-2 regulatory miRNAs. Analysis of PTPN11 levels by quantitative (q) PCR revealed that miR-758-3p increased, while miR-514a-3p reduced PTPN11 expression. The expression of miR-514a-3p and miR-758-3p within the human placenta was confirmed by qPCR; miR-514a-3p (but not miR-758-3p) levels inversely correlated with PTPN11 expression. To assess the interaction between these miRNAs and PTPN11/SHP-2, specific mimetics were transfected into first-trimester human placental explants and then cultured for up to 4 days. Overexpression of miR-514a-3p, but not miR-758-3p, significantly reduced PTPN11 and SHP-2 expression. microRNA-ribonucleoprotein complex (miRNP)-associated mRNA assays confirmed that this interaction was direct. miR-514a-3p overexpression attenuated IGF-I-induced trophoblast proliferation (BrdU incorporation). miR-758-3p did not alter trophoblast proliferation. These data demonstrate that by modulating SHP-2 expression, miR-514a-3p is a novel regulator of IGF signalling and proliferation in the human placenta and may have therapeutic potential in pregnancies complicated by altered placental growth.

STUDY OF MORPHOLOGY AND HISTOLOGY OF PLACENTA IN HYPERSENSITIVE MOTHERS

Background: Hypertensive pregnancy may be responsible for vascular damage, enhanced systemic inflammation and insulin resistance in the placenta as oxygen and nutrient transfer is impaired and oxidative stress is generated affecting the placental growth and development. Placental growth pattern in hypertensive pregnancies shows a variable pattern owing to placental insufficiency. Method: The study was carried out on 80 sets placentae, mothers and their babies. The placentae were collected from Obstetrics & Gynecology Department of NSCB Medical College Jabalpur. Out of 80 placentae, 40 were from normal pregnant mothers and 40 from pregnancies complicated by PIH in previously normotensive women, serial number of placentae, mother and baby were same. placentae were collected soon after the normal vaginal delivery or caesarian section along with 10 cm long stump of umbilical cord. Aims and objectives: The aim of this study was to determine whether maternal PIH would affect the morphology and histology of placenta and compare this with that of normotensive mothers. It was a cross-sectional comparative study carried out at the maternity ward and anatomy department of NSCB Medical College, Jabalpur. Result: A Macroscopic study of the placenta revealed placental weight, placental volume, diameter, placental thickness and number of cotyledons were less in study group. Mean placental weight in study group was 336gm and in control group was 425 (p<0.05). Mean placental volume in study group & control group were 236and352 ml respectively (p<0.05). Mean number of cotyledons were 14.7and 16 in study & control group respectively but not significant and mean diameter15.6 cms and17.05cms in study and control group. But in the present study placental thickness was not significant (p<0.539). There was a single umbilical artery present in one patient in PIH group. All morphometric parameters of placenta weight, volume, diameter, thickness, no. of cotyledons were reduced.
 Histological findings were cytotrophoblastic cellular proliferation, syncitial knot formation, fibrin plaque formation. In 20 percent cases, villi were hypovascular. The hypovascular villi have abundance of syncitial knots, usually lack vasculosyncitial membrane and increased stromal collagen. Conclusion: PIH adversely affect both morphology and histology of placenta.
 Keywords: morphology, histology, placenta, hypersensitive & mothers.

Cell dynamics in human villous trophoblast

Villous cytotrophoblast (vCTB) is a precursor cell population that supports the development of syncytiotrophoblast (vSTB), the high surface area barrier epithelium of the placental villus, and the primary interface between maternal and fetaltissue. In light of increasing evidence that the placenta can adapt to changing maternal environments or, under stress, can trigger maternal disease, we consider what properties of these cells empower them to exert a controlling influence on pregnancy progression and outcome. How are cytotrophoblast proliferation and differentiation regulated in the human placental villus to allow for the increasing demands of the fetaland environmental challenges and stresses that may arise during pregnancy? PubMed was interrogated using relevant keywords and word roots combining trophoblast, villus/villous, syncytio/syncytium, placenta, stem, transcription factor (and the individual genes), signalling, apoptosis, autophagy (and the respective genes) from 1960 to the present. Since removal of trophoblast from its tissue environment is known to fundamentally change cell growth and differentiation kinetics, research that relied exclusively on cell culture has not been the main focus of this review, though it is mentioned where appropriate. Work on non-human placenta is not systematically covered, though mention is made where relevant hypotheses have emerged. The synthesis of data from the literature has led to a new hypothesis for vCTB dynamics. We propose that a reversible transition can occur from a reserve population in G0 to a mitotically active state. Cells from the in-cycle population can then differentiate irreversibly to intermediate cells that leave the cycle and turn on genes that confer the capacity to fuse with the overlying vSTB as well as other functions associated with syncytial barrier and transport function. We speculate that alterations in the rate of entry to the cell cycle, or return of cells in the mitotic fraction to G0, can occur in response to environmental challenge. We also review evidence on the life cycle of trophoblast from the time that fusion occurs, and point to gaps in knowledge of how large quantities of fetal DNA arrive in maternal circulation. We critique historical methodology and make a case for research to re-address questions about trophoblast lifecycle and dynamics in normal pregnancy and the common diseases of pre-eclampsia and fetal growth restriction, where altered trophoblast kinetics have long been postulated. The hypothesis requires experimental testing, moving research away from currently accepted methodology towards a new standard that includes representative cell and tissue sampling, assessment of cell cycle and differentiation parameters, and robust classification of cell subpopulations in villous trophoblast, with due attention to gestational age, maternal and fetal phenotype, disease and outcome.

Study of histological changes of placenta in pregnancy-induced hypertension in poorvanchal region of Uttar Pradesh, India

Introduction: The placenta is a fetomaternal organ. It is a connection of the fetus with the uterine wall of mother. Through the placenta, exchange of gases and nutrient supply takes place. Through the placenta, fetal blood tissue comes in direct contact with the maternal blood without any rejection. It is a special transient organ of pregnancy. In our study, we carried out the microscopic examination of the placenta in pregnancy-induced hypertension, i.e., syncytial knot, cytotrophoblastic cellular proliferation, fibrinoid necrosis, endothelial proliferation, and calcified villous spot. Material and Methods: One hundred and fifty-two placentas of full-term pregnancy were collected from the labor room/operation theater of the Gynecology and Obstetrics Department of the Government Medical College and Superfacility Hospital Azamgarh. Out of one hundred and fifty-two placentas, 76 cases were controls from mothers with no known history of preexisting hypertension and 76 were collected from mothers with pregnancy-induced hypertension. Placentas were kept in 10% formalin for 24 h for fixation. After 24 h, tissues of placentas were passed through a series of the procedures from dehydration and clearing to wax impregnation before being sectioned from automated microtome. Time took for processing was 24 h. Five microns thick tissues sections were cut. Prepared slides were mounted in DPX and covered with the cover slip. Through binocular light, microscope slides were examined at ×10, ×40, and ×100 magnifications. Results: Histology in our study revealed that syncytial knots were present in placentas of all 100% of hypertensive and only 32.89% of normotensive mothers. Cytotrophoblastic proliferation was seen in 98.68% and 19.73% placentas of hypertensive and normotensive mothers, respectively. Fibrinoid necrosis of placenta was found in 88.15% of hypertensive and only 28.94% of normotensive mothers. The 100% placentas of the hypertensive mothers had endothelial proliferation as compared to controls. Calcified villous spots were seen in 84.21% and 31.57% of placentas of hypertensive and normotensive mothers, respectively. Discussion and Conclusion: Pregnancy-induced hypertension adversely affects the health of the fetus through its harmful effects on the placentas. Syncytial knots, cytotrophoblastic cellular proliferation, fibrinoid necrosis, endothelial proliferation, and the calcified villous spots were present more in the placentas of hypertensive mothers in our study in comparison to the study of other authors. In our research, we found that endothelial proliferations were present in all placentas. If proper treatment is given to the mother in the early stage of pregnancy, it may prevent the death of a fetus. Hence, this study helps the clinician for early diagnosis and treatment of pregnancy-induced hypertension.

PAR1&2 driven placenta EVT invasion act via LRP5/6 as coreceptors.

While the involvement of protease-activated receptors (PARs) in the physiological regulation of human placenta development, as in tumor biology, is recognized, the molecular pathway is unknown. We evaluated the impact of PAR1 and PAR2 function in cytotrophoblast (CTB) proliferation and invasion in a system of extravillous trophoblast (EVT) organ culture and in human cell-lines. Activation of PAR1 - and PAR2 -induced EVT invasion and proliferation, while the shRNA silencing of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) inhibited these processes. PAR1 and PAR2 effectively induce β-catenin stabilization in a manner similar to that shown for the canonical β-catenin stabilization pathway yet independent of Wnts. Immunoprecipitation analyses and protein-protein docking demonstrated the co-association between either PAR1 or PAR2 with LRP5/6 forming an axis of PAR-LRP5/6-Axin. Noticeably, in PAR1 -PAR2 heterodimers a dominant role is assigned to PAR2 over PAR1 as shown by inhibition of PAR1 -induced β-catenin levels, and Dvl nuclear localization. This inhibition takes place either by shRNA silenced hPar2 or in the presence of a TrPAR2 devoid its cytoplasmic tail. Indeed, TrPAR2 cannot form the PAR1 -PAR2 complex, obstructing thereby the flow of signals downstream. Elucidation of the mechanism of PAR-induced invasion contributes to therapeutic options highlighting key partners in the process.

Delta-9-tetrahydrocannabinol disrupts mitochondrial function and attenuates syncytialization in human placental BeWo cells.

The psychoactive component in cannabis, delta‐9‐tetrahydrocannabinol, can restrict fetal growth and development. Delta‐9‐tetrahydrocannabinol has been shown to negatively impact cellular proliferation and target organelles like the mitochondria resulting in reduced cellular respiration. In the placenta, mitochondrial dysfunction leading to oxidative stress prevents proper placental development and function. A key element of placental development is the proliferation and fusion of cytotrophoblasts to form the syncytium that comprises the materno‐fetal interface. The impact of delta‐9‐tetrahydrocannabinol on this process is not well understood. To elucidate the nature of the mitochondrial dysfunction and its consequences on trophoblast fusion, we treated undifferentiated and differentiated BeWo human trophoblast cells, with 20 µM delta‐9‐tetrahydrocannabinol for 48 hr. At this concentration, delta‐9‐tetrahydrocannabinol on BeWo cells reduced the expression of markers involved in syncytialization and mitochondrial dynamics, but had no effect on cell viability. Delta‐9‐tetrahydrocannabinol significantly attenuated the process of syncytialization and induced oxidative stress responses in BeWo cells. Importantly, delta‐9‐tetrahydrocannabinol also caused a reduction in the secretion of human chorionic gonadotropin and the production of human placental lactogen and insulin growth factor 2, three hormones known to be important in facilitating fetal growth. Furthermore, we also demonstrate that delta‐9‐tetrahydrocannabinol attenuated mitochondrial respiration, depleted adenosine triphosphate, and reduced mitochondrial membrane potential. These changes were also associated with an increase in cellular reactive oxygen species, and the expression of stress responsive chaperones, HSP60 and HSP70. These findings have important implications for understanding the role of delta‐9‐tetrahydrocannabinol‐induced mitochondrial injury and the role this might play in compromising human pregnancies.

Placental pathology in different degrees of pregnancy induced hypertension

Introduction: Pregnancy induced hypertension (PIH), a well-known medical complication of pregnancy is potentially morbid for the foeto-maternal health. It is also responsible for perinatal morbidity and mortality due to its effects on the growing foetus. Objectives: The present study was undertaken to analyse the histomorphological and gross features of placenta in pregnancy induced hypertension in relation to severity of hypertension, age of the patient, parity and gestational age. Materials and Methods: The current study was done at Gandhi Hospital, Secunderabad, India on antenatal cases of PIH of varying degrees. The placentas of these patients following delivery were studied and statistic significance between different histologic findings and severity of PIH calculated. Results: Incidence of PIH was highest in women above 26yrs of age (42%) and was found to be almost equal in both multiparous (52%) and primiparous (48%) women. Foetal outcome was worst in severe PIH (IUGR of 28.8% and IUD of 17.85%). The gross abnormalities noted, retroplacental hematomas (42%) and small sized placentae (24%) were more often seen in severe PIH. The consistent histological changes observed include fibrinoid necrosis (86%), thickened basement membrane (74%), increased syncitial knots (72%), stromal fibrosis (54%), cytotrophoblastic proliferation (46%), intervillous haemorrhage (40%), and calcification (34%). Conclusion: The pathological changes in the placenta seen in PIH patients are almost equally prevalent irrespective of the parity. Cases with severe PIH displayed features of placental underperfusion more frequently than with mild to moderate PIH. Hence watchful individualized management of PIH helps reduce the incidence of complications and morbidity.

CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF PLACENTA DYSFUNCTION IN PREGNANT WOMEN PRONE TO TOBACCO SMOKING

The aim is to determine the morphological markers of placental dysfunction in pregnantwomen under conditions of tobacco smoking.Material and methods. We examined 75 pregnant women (main group) who wereregistered and gave birth in the Odessa Maternity Hospital №7. Pregnant women in themain group were divided into 2 subgroups: 1-A group consisted of 45 pregnant womenwho smoked cigarettes during pregnancy; The 1-B group consisted of 30 pregnantwomen who smoked cigarettes before pregnancy and did not abuse tobacco during theircurrent pregnancies. The control group consisted of 40 healthy pregnant women whowere not under the influence of tobacco smoking during pregnancy. The examination ofpregnant women was conducted in accordance with local protocols of the OdessaMaternity Hospital №7 and regulating orders of the Ministry of Health of Ukraine.Results. The article presents the data of the clinical-morphological characteristics ofplacental dysfunction in pregnant women who are predisposed to tobacco smoking. Ithas been shown that smoking in pregnant women leads to an increase in the frequency ofobstetric complications, a malfunction of the fetoplacental complex and the condition ofthe fetus. The peculiarities of morpho-functional changes in villi chorion, which serve asthe basis for the development of chronic placental dysfunction under the conditions oftobacco smoking, are established. Decreased concentration of marker of placental dysfunction - placental lactogen in syncytiotrophoblast indicate a violation of maturationof trophoblast of the chorial villi.Conclusions. 1. Pregnant women, prone to tobacco smoking are a high-risk group ofplacental dysfunction and obstetric complications. 2. In pregnant women, who abusesmoking, manifestations of fetoplacental dysfunction occur by delaying the maturationof the chorial villi, proliferation of cytotrophoblast of intermediate mature and terminalvilli increases.

Human Trophoblast Differentiation Is Associated With Profound Gene Regulatory and Epigenetic Changes.

Defective placental implantation and vascularization with accompanying hypoxia contribute to preeclampsia (PE), a leading cause of maternal and neonatal morbidity and mortality. Genetic and epigenetic mechanisms underlying differentiation of proliferative cytotrophoblasts (CytTs) to multinucleated syncytiotrophoblast (SynT) are incompletely defined. The SynT performs key functions in nutrient and gas exchange, hormone production, and protection of the fetus from rejection by the maternal immune system. In this study, we used chromatin immunoprecipitation sequencing of midgestation human trophoblasts before CytT and after SynT differentiation in primary culture to analyze changes in binding of RNA polymerase II (Pol II) and of active and repressive histone marks during SynT differentiation. Our findings reveal that increased Pol II binding to promoters of a subset of genes during trophoblast differentiation was closely correlated with active histone marks. This gene set was enriched in those controlling immune response and immune modulation, including interferon-induced tetratricopeptide repeat and placenta-specific glycoprotein gene family members. By contrast, genes downregulated during SynT differentiation included proinflammatory transcription factors ERG1, cFOS, and cJUN, as well as members of the NR4A orphan nuclear receptor subfamily, NUR77, NURR1, and NOR1. Downregulation of proinflammatory transcription factors upon SynT differentiation was associated with decreased promoter enrichment of endogenous H3K27Ac and H3K9Ac and enhanced binding of H3K9me3 and histone deacetylase 1. However, promoter enrichment of H3K27me3 was low in both CytT and SynT and was not altered with changes in gene expression. These findings provide important insight into mechanisms underlying human trophoblast differentiation and may identify therapeutic targets for placental disorders, such as PE.

Histopathological study of placental changes associated with pre-eclampsia and eclampsia in a tertiary care centre of Puducherry

Histopathological study of placental changes associated with pre-eclampsia and eclampsia in a tertiary care centre of Puducherry - ACHR- Print ISSN No: - 2581-5725 Online ISSN No:- 2456-9267 Article DOI No:- 10.18231/2456-9267.2019.0009, IP Archives of Cytology and Histopathology Research-IP Arch Cytol Histopathol Res

GNG7 silencing promotes the proliferation and differentiation of placental cytotrophoblasts in preeclampsia rats through activation of the mTOR signaling pathway.

Preeclampsia (PE) is a pathological condition that manifests during pregnancy as the occurrence of an abnormal urine protein level and increased blood pressure due to inadequate cytotrophoblast invasion. To elucidate the mechanism underlying PE, the present study primarily focused on the regulatory effects and mechanism of the G protein γ 7 (GNG7) on placental cytotrophoblasts in a rat PE model. Initially, the PE model was established with 45 specific pathogen-free Sprague-Dawley rats (30 females and 15 males). The expression patterns of GNG7, 4E-binding protein 1 (4E-BP1), phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) and mammalian target of rapamycin (mTOR) were examined in the PE rats. Placental cytotrophoblasts isolated from normal and PE rats were treated with a small interfering RNA against GNG7, mTOR signaling pathway activator (HIV-1 Tat) or inhibitor (rapamycin). Following treatment, cell proliferation, differentiation and apoptosis were evaluated, and mTOR signaling pathway-related factors (4E-BP1, p70S6K and mTOR), cell proliferation-related factors (vascular endothelial growth factor and transforming growth factor-β1), differentiation-related factors [activator protein-2 (AP-2)α and AP-2γ], and apoptosis-related factors [B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein] were determined. Finally, soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) levels were measured via enzyme-linked immunosorbent assay. Initially, the mTOR signaling pathway was inactivated in the placental tissues and cytotrophoblasts in the PE rats. Silencing GNG7 reduced the levels of sFlt-1 and sEng and activated the mTOR signaling pathway. Silencing of GNG7 or activation of the mTOR signaling pathway enhanced cell proliferation and differentiation, but inhibited the apoptosis of placental cytotrophoblasts in the PE rats. Taken together, the results showed that GNG7 silencing repressed apoptosis and enhanced the proliferation and differentiation of placental cytotrophoblasts in PE rats through activation of the mTOR signaling pathway.

Partial hydatidiform mole and coexisting fetus during second trimester pregnancy

Introduction: Hydatidiform mole is an abnormal pregnancy characterized by proliferation of cytotrophoblast and synciotrophoblast and vesicular swelling of placental villi. Partial hydatidiform mole and coexisting fetus is a rare condition that presents a dilemma for physicians and the parents of the fetus, particularly when it is detected during the second trimester of pregnancy.

A Morphological Study of Placenta in Normal and Diabetic Pregnancies and Its Foetal Implications

Background: The placenta is a foeto-maternal organ that separates the maternal and foetal circulations and plays a key metabolic role in pregnancy. Placental changes are directly proportional to the disease duration and its severity. In addition foetal outcome is also adversely influenced by pathological changes in placenta. . In the present study the focus is to bring out placental changes specifically associated with diabetes Methods: The placentae for the study were obtained from the in- patients of department of Obstetrics and Gynaecology, Sree Gokulam Medical College and Research Foundation, Venjaramoodu. 100 placentae were collected for the study. Among these 50 placentae were from mothers with uneventful antenatal period comprising the normal group and 50 placentae from mothers with GDM classified as GDM group. A descriptive study was done to assess the morphology of placentae in Gestational diabetes mellitus and to compare the same with that of normal pregnancies. The parameters included both gross and microscopy. Result: The morphometric parameters and gross observations like hematoma and calcification were increased in GDM. Microscopic findings like Syncytial knots, fibrinoid necrosis, Cytotrophoblastic proliferation, basement membrane thickening, obliterative endarteritis, Villous vascularity and villous stromal fibrosis (p<0.001) were significantly increased in GDM group. Significant percentage of placentae with more than 5% of immature villi was seen in GDM group. The birth weight of babies was increased in GDM group mothers compared to normal group Conclusion: Diabetes in pregnancy has a profound impact on both the placenta and the foetus. Both the villous and stromal parameters are altered by the high glycemic level.

Androgen and estrogen receptors in placental physiology and dysfunction

The placenta is recognized as an endocrine organ, largely due to its secretions of steroid hormones, including progesterone, androgens, and estrogens. Steroid hormones play an essential role in the progression of pregnancy, fetal development, and growth. Furthermore, steroids are necessary for establishment and maintenance of a normal pregnancy, preparing the endometrium for implantation, stimulating endometrial secretions, and regulating uterine blood flow, however the exact mechanism of sex steroid signaling through their receptors in placental function is unknown. In this review, we will provide an overview of the current knowledge on sex steroid receptors in normal placental development, as well as evidence of abnormal signaling associated with placental dysfunction. A systematic literature search was performed using the NCBI PubMed search engine, including the following key works: estrogen receptor, androgen receptor, placenta, placental development, cytotrophoblast, and differentiation. Of the over 700 articles that were returned, 125 studies focused on estrogen and androgen receptors in human placenta development and function during normal and abnormal pregnancy, as well as in rodents and ruminants placentae. Receptors for both estrogens and androgens have been localized within the mammalian placenta, but surprisingly little is known about their signaling in trophoblast cell differentiation and function. An emerging picture is developing in which estrogen receptors possibly play role in cytotrophoblast proliferation and extravillous trophoblast invasion, whereas androgen receptors are involved in syncytiotrophoblast differentiation and function.

Placental Peripartum Pathologies in Women with Preeclampsia and Eclampsia.

Objective To determine the pattern of pathological changes in placentas of preeclamptic/eclamptic parturients and its correlation with the clinical severity as well as the perinatal outcome. Methods A cross-sectional analytical study of placental pathologies in preeclamptic/eclamptic patients was performed in a blinded pattern and compared with matched normal controls. Data were analyzed using Epi-Info 2008 version 3.5.1. Results Placental pathologies were evaluated in 61 preeclamptic/eclamptic patients and in 122 controls. Of the 61 placentas, 53 (4.7%) were of preeclampsia while 8 (0.71%) were of eclampsia. Of the preeclamptic group, 14 (23%) had mild preeclampsia while 39 (63.9%) had severe preeclampsia. Infarction, haematoma, and some histological changes increased with the severity of preeclampsia (p < 0.001). When comparing placentas in eclampsia, severe preeclampsia, mild preeclampsia, and normal controls, there was respective increase in the presence of any infarction (75%, 66.7%, 35.7% vs. 12.3%) or any haematoma (100%, 100%, 71.4% vs. 35.2%), decidual arteriopathy (87.5%, 76.9%, 64.3% vs. 35.2%), cytotrophoblastic proliferation (75%, 71.8%, 42.9% vs. 25.4%), and accelerated villous maturation (75%, 69.2%, 57.1% vs. 31.1%). There was no statistically significant difference in placental calcifications, stromal oedema, stromal fibrosis, and syncytial knots. Degree of placental infarction was correlated with the fetal birth weight. The fetal birth weight with placental involvement of >10% was significant (p=0.01). Conclusion In mild or severe preeclampsia/eclampsia, placentas had significant histological signs of ischaemia and degree of placental involvement by infarction is inversely proportional to fetal birth weight. While feto-placental ratio was higher with increased severity of the disease, the mean weight was less. This trial is registered with researchregistry3503.