Stem Villi Research Articles

MORPHOMETRIC PARAMETERS OF MATURITY OF PLACENTAL CHORINAL VILLI IN PREMATURE LABOR

Aim – to establish some morphometric parameters of placental villi in premature birth in comparison with physiological pregnancy.Material and methods. The material (30 placentas in premature births and 30 placentas in physiological pregnancies) was fixed for 22-24 hours in a neutral buffered 10% formalin solution. Next, the material was dehydrated in an ascending battery of alcohols and embedded into paraffin at 580С. Serial histological sections 5 μm thick were made on a sled microtome. After deparaffinization, serial histological sections were stained with hematoxylin and eosin, and with a chromotrope - water blue according to N.Z.Slinchenko. In addition to the descriptive method of histopathological examination, computer morphometry was performed on previously obtained digital copies of optical microscopic images of the tissue (Delta Optical Evolution 100 microscope {planachromatic lenses according to the required optical magnification} and Olympus SP550UZ digital camera). Digital copies of the image were analyzed using a freeware copy of the ImageJ v1.52 computer program specialized for digital histometric studies. In particular, the percentage of different types of chorionic villi was calculated on digital copies of optical images using the unrepeatable score test method. The obtained digital data were processed statistically. In particular, with the help of a copy of the free (freeware) computer program for statistical calculations PAST v 4.14, a preliminary test for the normality of the distribution was applied according to the Wilkie-Hahn-Shapiro test. For all studied statistical samples, according to this criterion, the hypothesis about the normality of the distribution was not rejected (at p=0.05), therefore, parametric methods of statistical analysis were used: calculation of the arithmetic mean and its error, the odd two-sided Student's test. Along with the Student's test, the non-parametric Mann-Whitney U test was also used. Results. It was considered most important to start assessing the state of the placenta according to the percentage ratios between different types of villous formations. In particular, according to modern ideas about different types of chorionic villi in the II and III trimesters of pregnancy, the following types of villous formations of the placenta were distinguished: stem villi ("early" and late"), intermediate villi (immature and mature), terminal villi, terminal "specialized" villi, mesenchymal villi, embryonic villi, trophoblastic and villous processes. The total amount of the specified villi should be equal to 100%. The division of villi into primary, secondary, and tertiary villi is relevant only for the 1st trimester of pregnancy, therefore, it is not suitable for studying the morphological features of premature birth.Conclusions. According to the obtained morphometric data, the immaturity of the chorionic tree is noted in premature birth compared to physiological pregnancy. This can be seen from a noticeable increase in the percentage of stem "early" villi, intermediate immature and mature villi, mesenchymal and embryonic villi, trophoblastic and villous processes, but with a significant decrease in the percentage of terminal villi.

Placental differences between severe fetal growth restriction and hypertensive disorders of pregnancy requiring early preterm delivery: morphometric analysis of the villous tree supported by artificial intelligence

The "great obstetrical syndromes" of fetal growth restriction and hypertensive disorders of pregnancy can occur individually or be interrelated. Placental pathologic findings often overlap between these conditions, regardless of whether one or both diagnoses are present. Quantification of placental villous structures in each of these settings may identify distinct differences in developmental pathways. To determine how quantity and surface area of placental villi and vessels differ between severe, early-onset fetal growth restriction with absent/reversed umbilical artery Doppler indices, hypertensive disorders of pregnancy, and the two conditions combined among subjects with disease severity warranting early preterm delivery. We hypothesize that trajectories of placental morphogenesis diverge after a common initiating insult of deep defective placentation. Specifically, we postulate that only villi are affected in pregnancy-related hypertension, whereas both villous and vascular structures are proportionally diminished in severe fetal growth restriction, with no additional effect when hypertension is concomitantly present. In this retrospective cohort study, paraffin-embedded placental tissue was obtained from four groups: [1] Severe fetal growth restriction with absent/reversed umbilical artery end-diastolic velocities and hypertensive disorders of pregnancy, [2] Severe fetal growth restriction with absent/reversed umbilical artery Doppler indices and no hypertension,[3] Gestational age-matched, appropriately grown pregnancies with hypertensive disease, and [4] Gestational age-matched, appropriately grown pregnancies without hypertension. Dual immunohistochemistry for cytokeratin-7 (trophoblast) and CD34 (endothelial cells) was performed followed by artificial intelligence-driven morphometric analyses. Number of villi, total villous area, number of fetoplacental vessels, and total vascular area across villi within a uniform region of interest were quantified. Quantitative analyses of placental structures were modeled with linear regression. Placentas from pregnancies complicated by hypertensive disorders of pregnancy exhibited significantly fewer stem villi (-282 stem villi, 95% CI: [-467, -98], p<0.01), smaller stem villous area (-4.3 mm2, 95% CI: [-7.3, -1.2], p<0.01), and fewer stem villous vessels (-4967 stem villous vessels, 95% CI [-8501, -1433], p<0.01), with no difference in total vascular area. In contrast, placental abnormalities in severe growth restriction were limited to terminal villi, with global decreases in number of villi (-873 terminal villi, 95% CI: [-1501, -246], p<0.01), villous area (-1.5 mm2, 95% CI: [-2.7, -0.4], p<0.01), number of blood vessels (-5165 terminal villous vessels, 95% CI: [-8201, -2128], p<0.01), and vascular area (-0.6 mm2, 95% CI: [-1.1, -0.1], p=0.02). The combination of hypertension and growth restriction had no additional effect beyond the individual impact of each state. Pregnancies complicated by hypertensive disorders of pregnancy exhibited defects in the stem villi only, whereas placental abnormalities in severely growth restricted pregnancies with absent/reversed umbilical artery end-diastolic velocities were limited to the terminal villi. There were no significant statistical interactions with the combination of growth restriction and hypertension, suggesting that distinct pathophysiologic pathways downstream of the initial insult of defective placentation are involved in each entity and do not synergize to result in more severe pathologic consequences. Delineating mechanisms underlying the divergence in placental development after a common inciting event of defective deep placentation may shed light on new targets for prevention or treatment.

Results of the morphological and immunohistochemical study of the consequences in premature birth and premature rupture of the membrane

The article presents the results of a morphological and immunohistochemical study of the afterbirths of women with miscarriages in cases of premature rupture of membranes (PRPO).The aim: to study the morphological and immunohistochemical features of placentas in premature births and premature rupture of membranes and to conduct a comparative analysis of the results depending on the gestational period.Material and methods. A morphological and immunohistochemical study of the litters of 250 pregnant women (the main group) with spontaneous premature births at 22-36 weeks of gestation and premature rupture of the membranes, which took place on the basis of the Department for Pregnant Women with Obstetric Pathology of the PAG Institute named after Acad. OHM. Lukyanova National Academy of Sciences of Ukraine" for the period from 2018 to 2020. The women of the main group are divided into three groups depending on the date of delivery - the 1st group includes patients who gave birth at 22-28 weeks of pregnancy, patients of the 2nd group who gave birth at 29-33 weeks, and to the 3rd group - those who gave birth at 34-36 weeks of pregnancy. Placentas of pregnant women of the main group were examined using morphological (histological method - staining with hematoxylin and eosin and van Gieson) and immunohistochemical methods (indirect streptavidin-peroxidase method for determining the expression level of progesterone receptors - RP).Results and discussion. Premature maturation of chorionic villi was found in 40 % of placentas of women in the 1st group 1, in 20 % – blood circulation disorders and the presence of acute inflammatory infiltration in the fetal membranes, decidual and chorionic membranes, 10 % – pathological immaturity of the placenta according to the variant of chaotic sclerosed villi. During the immunohistochemical study of RP, an unexpressed reaction was found in the epithelium and stromal cells of the stem, intermediate and terminal villi – 1 point; in fetal membranes and extra-villous cytotrophoblast – 2 points; in the endothelium of vessels – 0–1 point. In the placentas of women in the 2nd and 3nd group premature maturation of villi was found in 70 % of cases, pseudo-infarcts of villi which are embedded in fibrinoid occupying a significant area – 45 %, afunctional zones – 55 %, blood circulation disorders – 35 %, pathological immaturity placenta according to the variant of chaotic, sclerosed villi – 20 %, acute inflammatory infiltration in the fetal membranes – 15 %. Immunohistochemical analysis of the placental barrier revealed the highest expression of RP in the nuclei of decidual cell which belong to the maternal structure. Of note is the presence of progesterone receptor expression in stem villi, fibroblasts, and vessel wall nuclei. Minimal or absent expression was determined in the nuclei of other villous structures and their vessels. Conclusions. It has been proven that the receptivity of progesterone has its own characteristics in placental structures depending on the gestation period, which is an important factor in the choice of management for the prevention and reduction of perinatal losses for this contingent of pregnant women. The conducted studies make it possible to formulate a clear concept of pathogenetically justified therapy for miscarriage.

Morphometric and immuno-biochemical markers of placenta in patients with uterine eclampsia

Purpose: to study the segmentation of organometric and immuno-biochemical digital indicators in ewes with ESO at the end of gestation.Materials and methods. The experiment involved three flocks of Tsygai, Volgograd and Stavropol breeds, each with 700 suyag sheep. Placental tissue samples were taken from clinically healthy and sick pregnant ewes, which were placed in 10% neutral formalin. Using a Cytadel 2000 histoprocessor (Shendon), the obtained samples were clarified in chloroform and enclosed in a Histomix paraffin medium (Biovitrum). Histosections were prepared on a rotary microtome (MICROM HM340E). Using the AxioScope.A1 (ZEISS) microscope, histopreparations were photographed and processed using the ZENpro 2012 (ZEISS) program. According to Schmidt and Thannhauser, the RNA content was determined using a two-wave spectrophotometer in UV. The activity of the G-6-Phase was studied by Swanson. In vacuum tubes Vacuette ™ (Austria), blood samples were taken in the morning before feeding, from the jugular vein. Results. In sheep with eclampsia, a decrease in the total mass of the placenta, its cotiledons, as well as an increase in the length of the umbilical cord, in which stroma sclerosis is noted in the vascular wall, was observed. Small calcification foci were found in the tissues of the afterbirth, and small terminal villi are located around the stem villi near the vascular membrane, tightly adjacent to them. The proportion of syncytiotrophoblast of crypts of carbuncles and villi of the chorion of cotyledons of mature syncytium decreases in comparison with physiologically occurring severity. The content of RNA in its subcellular fractions is mainly concentrated in the microsomal fraction, 18% - in mitochondria and 7% - in the nuclear fraction. Albumins in pregnant ewes with eclampsia were reduced by 1.35 times. BASC and phagocytic activity of leukocytes in queens with eclampsia of pregnant sheep is reduced 15 days before lambing, which poses a threat to the reproductive health of the mother and the viability of newborn lambs.

Utility of the Movat pentachrome stain technique in the microanatomical analysis of the human placenta

The efficacy and utility of pentachrome staining has been demonstrated in many studies on diverse human body tissues. Movat pentachrome technique is used for multicolor staining of tissue sections and vascular and stroma visualization. So far, the utility of this method for microanatomical evaluation of placental structures has not been demonstrated. The aim of this study is to evaluate the image of normal placenta and to develop some reference images for future evaluation of pathological tissues based on this technique. Material and method. The study was carried out on 21 paraffin slices taken from seven mature human placenta of single pregnant women without significant pathology and completed with a planned, elective Caesarean section. All paraffin slices were used for preparation of tissue microarrays and then performing a histochemical staining (HE and Movat). Results. On the basis of the collected material, microscopic analysis enabled the identification of normal placental villi - terminal villi,mature intermediate villi and stem villi. Moreover the maternal part of placenta was visualized. It is worth emphasizing that in each case not only the trophoblast but also the stroma structures were visualized. Conclusions. This study proved the effectiveness and usefulness of Movat imaging of placenta especially in visualization of the stroma.

MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL FEATURES OF PLACENTA AND PLACENTAL FACTOR IN WOMEN WITH ISOLATED CONGENITAL HEART DEFECTS IN NEWBORN

Introduction. Congenital heart defects (CHD) in fetus can affect the course of pregnancy, cause changes in the functioning of the pregnant woman's systems and metabolic and hemodynamic disorders. The relevance of the problems CHD is primarily due to their high frequency in newborns (5-9 per 1,000 live births) depending on geographical differences and the significant share among multiple congenital malformations and the need for surgical treatment in the neonatal period. Placenta, as one of the least studied human organs, plays not only a crucial role in the process of organogenesis, but also in the "programming" of human health after fetal and newborn periods. For today, it’s important to determine the association between the CHD and placental abnormalities, the nature and consequences of which need further study.Objective. To study morphological and immunohistochemical features of placental structures in parturients with isolated congenital heart defects in the newborn.Material and methods. Over the period 2020-2021, 90 pregnant women aged 17 to 39 years (mean age 28.36±5.08) who gave birth at 37-41 weeks, and their placents, of which 30 had different forms of CHD in the newborn, were examined on a hospital-based sample. Patients were divided into two groups: the study - women with CHD in the newborn, and control - somatically healthy motherswith healthy children. Given the different etiologies of cardiovascular defects in fetus, as well as the presence of different risk factorsfor their occurrence, in order to minimize their impact on the emergence of isolated CHD, considered appropriate selection criteria for pregnant women with non-syndromic forms of cardiovascular defects, as the presence of genetic syndrome can affect intrauterine fetaldevelopment, which makes it impossible to determine a single effect of CHD development. The selection criteria in this study included:somatically healthy woman, unburdened pregnancy, natural insemination (without using of reproductive technologies), the presence of isolated heart disease in the fetus, confirmed by a cardiologist using echocardiography. Organometric, macroscopic, general histological and immunohistochemical methods were used to study placental morphology and placental factors.Results. Analyzing the data on the morphological features of placentas from women with CHD in the newborn, we should note the presence of circulatory disorders in 60% of cases, namely multiple infarcts, complete or partial obliteration of arteries and arterioles with perivascular fibrosis (in the stem villi – 15%, intermediate – 10%, terminal - 10%), reduced number of fetal vessels in the terminal villiand syncytiocapillary membranes, abrupt vasodilation of intermediate villi. Complete or partial replacement of villous epithelium by fibrinoid masses in 20% was also detected. Immunohistochemical study of placental growth factor showed less pronounced expression in syncytia, decidual sheath and stromal cells (1-2 points) compared with control (2-3 points).Conclusions. The revealed morphological and immunohistochemical changes in the placental barrier at different levels refer to the damage of maternal and fetal placenta structures of parturients with isolated neonatal heart disease, which lead to impaired stromalvascular processes with reduced perfusion. This confirms the world data on the presence of placental-cardiac axis and can be a predictor of CHD at the early stages of placental structure study, as well as in further prediction of the child's health.

Immunohistochemical features of expression of progesterone receptors of placental structures in premature birth

The objective: to study the immunohistochemical features of placenta in women with premature birth in 28–33 weeks of pregnancy. Materials and methods. 120 pregnant women (the main group) who were hospitalized and delivered in the Kyiv Perinatal Center during 2018–2020 at a gestation period of 23–33 weeks were examined. The women of the main group were divided into two subgroups depending on the term of birth – the 1st group included patients who delivered at 23–28 weeks of pregnancy, the patients of the 2nd group had labors at 29–33 weeks. Placentas of women in the main group were examined using morphological (histological method – staining with hematoxylin and eosin and van Gieson) and immunohistochemical methods (indirect streptavidin-peroxidase method for determining the expression level of progesterone receptors – PR). Results. Premature maturation of chorionic villi was found in 40 % of placentas of women in the 1st group 1, in 20 % – blood circulation disorders and the presence of acute inflammatory infiltration in the fetal membranes, decidual and chorionic membranes, 10 % – pathological immaturity of the placenta according to the variant of chaotic sclerosed villi. During the immunohistochemical study of RP, an unexpressed reaction was found in the epithelium and stromal cells of stem, intermediate and terminal villi – 1 point; in fetal membranes and extravillous cytotrophoblast – 2 points; in the endothelium of vessels – 0–1 point. In the placentas of women in the 2nd group premature maturation of villi was found in 70 % of cases, pseudoinfarcts of villi which are embedded in fibrinoid occupying a significant area – 45 %, afunctional zones – 55 %, blood circulation disorders – 35 %, pathological immaturity placenta according to the variant of chaotic, sclerosed villi – 20 %, acute inflammatory infiltration in the fetal membranes – 15 %. Immunohistochemical analysis of the placental barrier revealed the highest expression of RP in the nuclei of decidual cell which belong to the maternal structure. It should be noted the presence of expression of progesterone receptors in stem villi, fibroblasts and nuclei of the vessel wall. Minimal or absent expression was determined in the nuclei of other villous structures and their vessels. Conclusions. It was established that the receptivity of progesterone has its own characteristics in placental structures depending on the gestation period, which is an important factor in the choice of management for the prevention and reduction of perinatal losses for this contingent of pregnant women.

Prenatal and Postnatal Zika Intrauterine Infection: Diagnostic Imaging Techniques and Placental Pathology

Introduction: Zika virus (ZIKV) is an arbovirus (arthropod-borne virus) in the genus Flavivirus and Flaviviridae family. In November 2015, several cases of microcephaly in Northeastern of Brazil suggested ZIKV involvement. Case Report: A 33-year-old primigravida developed fever and cutaneous rash at 7th week of gestation (WGA). The ultrasound and MRI examination showed head circumference < 5th centile and enlargement of lateral ventricles. The infant was delivered at 39th WGA with microcephaly. Microscopy of the placenta showed chronic villitis and intervillitis, nodular stromal fibrosis in the stem villi, and vascular thickening. Postnatal CT showed collapsed cranium due to growth impairment of the suprathalamic brain, multiple cerebral calcifications, parenchymal atrophy, and ventricular dilatation. Now, at 6 years old, the child suffers from severe neurologic symptoms, including seizures. Conclusion: This case gathers images of prenatal and postnatal period, and placental histopathology. The long-term follow-up highlights the dramatic neurological sequelae induced by ZIKV.

Fetal Vascular Ectasia Can be an Artifact of Placental Fixation.

Placentas from outlying hospitals are formalin-fixed en route to our laboratory. We identified that chorionic, stem villus, and umbilical vessels in these fixed placentas are ectatic with greater frequency than in our in-house fresh placentas. We searched our LIS for third trimester placentas using keywords "ectasia" or "ectatic" over a 12-month period. We fixed incoming in-house placentas over a 2-week period for 24-72hours and tabulated the presence or absence of vascular ectasia as defined by Parast et al, 2008. The LIS search identified 61% of placental cases from outlying hospitals that had ectatic vessels vs 3% of in-house placentas (P < .001). Of 38 placentas fixed in a 2-week period, 45% had ectatic chorionic or stem villus vessels and 21% had umbilical vessel ectasia. In comparison, in the 2 subsequent weeks, 3.8% (P < .001) of fresh placentas had vascular ectasia. These data suggest that large fetal vessels in the placenta become engorged with blood at delivery and, if fixed soon after delivery, remain ectatic and congested when processed for pathology. The identification of artifactual ectasia is important because fetal vessel ectasia can suggest the presence of fetal vascular malperfusion (FVM) if diagnostic signs of FVM are present.

Placental Super Micro-vessels Segmentation Based on ResNeXt with Convolutional Block Attention and U-Net.

Accurate placenta super micro-vessels segmentation is the key to diagnose placental diseases. However, the current automatic segmentation algorithm has issues of information redundancy and low information utilization, which reduces the segmentation accuracy. To solve this problem, we propose a model based on ResNeXt with convolutional block attention module (CBAM) and UNet (RC-UNet) for placental super micro-vessels segmentation. In the RC-UNet model, we choose the UNet as the backbone network for initial feature extraction. At the same time, we select ResNeXt-CBAM as the attention module for feature refinement and weighting. Specifically, we stack the blocks of the same topology following the split-transform-merge strategy to reduce the redundancy of hyperparameter. Moreover, we conduct CBAM processing on each group of the detailed features to get informative features and suppress unnecessary features, which improve the information utilization. The experiments on the self-collected data show that the proposed algorithm has better segmentation results for anatomical structures (umbilical cord blood (UC), stem villus (ST), maternal blood (MA)) than other selected algorithms.

Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts.

Preeclampsia is a common obstetric disorder affecting 2-8% of pregnancy worldwide. Fibrosis is an important histological change occurring in preeclamptic placenta, and might depend on the excess deposition of collagen I. However, the role of fibrotic placenta and collagen I in the pathogenesis of preeclampsia remains unclear. Therefore, we analyzed the collagen deposition and the expression of Collagen I in human placenta by Masson staining, Sirius red staining and western blotting. Further, the role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice. HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Human preeclamptic placenta exhibited a significantly higher degree of fibrosis in stem villi and terminal villi than normal placenta, and was characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational days 4.5–17.5, to a decrease in weight and number of embryos, and to enhanced placental collagen I expression and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonists of ERK and β-catenin. Moreover, transcriptome sequencing demonstrated that signaling pathways related to cell proliferation and invasion were significantly downregulated in HTR-8SV/neo cells. Thus, we propose that collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signaling pathways. Our findings could pave the way to the discovery of small-molecule inhibitors for preeclampsia treatment and future studies with larger sample size are required.

Collagen I Induces Preeclampsia-Like Symptoms by Suppressing Proliferation and Invasion of Trophoblasts

Background: Fibrosis is an important histological change occurring in preeclamptic placentas, and might depends on the excess deposition of collagen I. However, the role of fibrotic placentas and collagen I in the pathogenesis of preeclampsia remains unclear. Methods: Collagen deposition and the expression of Collagen I in human placentas were analysed by Masson staining, Sirius red staining and western blotting. The role of collagen I in preeclampsia pathogenesis was studied in C57BL/6 mice.HTR-8/SVneo cells were used to investigate the mechanisms underlying the effects of collagen I in trophoblasts by transcriptome sequencing and pharmacological agonists. Finding: Human preeclamptic placentas exhibited a higher degree of fibrosis in stem villi and terminal villi than normal placentas, and were characterized by collagen I deposition. In vivo, a single injection of collagen I on gestational day 0.5 led to an increase in systolic pressure of pregnant mice from gestational day 4.5 -17.5, to a decrease in weight and number of viable embryos, and to enhanced placental collagen I expression, and degree of fibrosis compared with control mice. In vitro, collagen I attenuated the proliferation and invasion of HTR-8SV/neo cells. This effect could be reversed by treatment with agonist s of ERK and β-catenin. Transcriptome sequencing demonstrated that pathways related to cell proliferation and invasion were significantly downregulated in HTR-8/SVneo cells. Interpretation: Collagen I induced preeclampsia-like symptoms by suppressing the proliferation and invasion of trophoblasts through inhibition of the ERK phosphorylation and WNT/β-catenin signalling pathways. Funding: National Natural Science Foundation of China and Guangdong Province. Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: The collection of placentas was approved by the Ethics Committee of Nanfang Hospital（NFEC-2017-055）. All participants gave written consent prior to donating their placenta.

Morphological and immunohistochemical parameters of chronic placental insufficiency in preeclampsia

Aim. To determine the morphological parameters of chronic placental insufficiency in pregnancy complicated by preeclampsia, also in women with chronic arterial hypertension (CAH).&#x0D; Materials and Methods. The analysis of history data, peculiarities of pregnancy and childbirth in women with hypertensive disorders was carried out. A review histology of 40 placentas in moderate preeclampsia, 40 placentas in severe preeclampsia, and 35 placentas of women with CAH and associated preeclampsia was performed. The control group consisted of 20 placentas of women with uncomplicated pregnancy without hypertensive disorders. Immunohistochemical examinations were performed on paraffin sections according to standard methods using primary goat antibodies to annexin V (R-20, sc-1929) and rabbit antibodies to erythropoietin (H-162, sc-7556) in a working dilution 1:200 with Super Sensitive IHC polymer detection system.&#x0D; Results. Based on the results of pathomorphological examination of placentas of women with hypertensive disorders, two forms of chronic placental insufficiency were identified. The defining form of placental insufficiency in women with CAH and associated preeclampsia was fetoplacental insufficiency, and in preeclampsia of moderate severity and in severe one utero-placental form of chronic placental insufficiency. Based on the study of the dynamics of expression of annexin V and erythropoietin, morphological parameters of the placental compensatory potential and placental hemostasis disorders in hypertensive disorders in pregnant women were determined.&#x0D; Conclusion. Diagnostic morphological criteria for fetoplacental insufficiency in women with hypertensive disorders are a combination of maternal and fetal malperfusion with obliterative angiopathy of stem villi vessels; in the utero-placental form obliterative angiopathy of spiral arteries, placental hypoperfusion with the development of local hypoxia and hemostatic disorders in the form of thrombosis of the intervillous space and villi infarcts.

Peculiarities of the inflammatory reactions development in placenta at delivery in different gestational terms

Objective of the study: to study peculiarities of the inflammatory reactions development in placenta according to results of a general histological and immunohistochemical study of the prevalence and intensity of reactions caused by CD45 and tumor necrosis factor α (TNF-α) during childbirth at different gestational periods.Materials and methods. Morphological and immunohistochemical studies of various placental structures and CD45 and TNF-α expression level in 142 women with preterm delivery at different gestational periods were performed: group I – at 23–29 weeks, group II – at 30–34 weeks; group III – at 35–36 weeks + 6 days, group IV (control) – 40 women at 38–40 weeks.Results. Inflammatory infiltration and the most expressive CD45 expression prevailed in the decidual membrane, TNF-α expression was predominantly negative in group I. In group II, inflammatory changes were evidenced by collagenization and stromal fibrosis, a decrease in fetal vessels, fibroblast proliferation, an increase in intervillous fibrinoid, and CD45 spread was expressed in decreasing order of intensity in decidual membrane, in stroma of intermediate villi and in stem villi. In group III, foci of inflammatory infiltration spread from the decidual membrane to the intervillous space and villi stroma, vessels plethora of all types of villi, dystrophic changes, and fibrinoid volume increased. CD45 expression was more common and expressive than in the groups I and II, and TNF-α expression was weakly positive only in the decidual membrane. The control group determined the widespread expressive CD45 expression in all placental structures and positive moderate TNF-α expression.Conclusions. Preterm delivery and delivery on term occur when there is an activation of inflammatory reactions in placenta. Inflammation in the placental structures is a necessary condition for development of the mother-fetal interphase, however, the features of local immune response prove the need to determine genetic mechanisms of the preterm labor.

Molecular and morphological peculiarities of chronic placental insufficiency formation caused by different types of diabetes mellitus

Рathogenesis of the chronic placental insufficiency is largely determined by the type of diabetes mellitus and the degree of its compensation. Trophic function failure of placenta changes its hormonal activity, formation of respiratory disorders and development of oxidative stress. The histological structure of placentas among patients with type 1 diabetes mellitus (T1D) is represented by reduced chorionic villi dimensions of all levels. Stromal edema and increased number of mesenchymal stromal cells are found in the stem and intermediate villi, and hypervascularisation and thickening of syncytiocapillary membranes are detected in terminal villi. In type 2 diabetes mellitus (T2D), the histological structure of the placenta may be represented as a premature maturation and abnormal immaturity of the villous tree with focal fibrosis of villi stroma, hypervascularisation of villi, abundance of syncytial nodules and infarction in the subchorial space. The peculiarity of the placenta structure in gestational diabetes mellitus is predominantly an intermediate immature type of development with angiogenesis abnormality. Angiogenesis processes failure and endothelial dysfunction in chorionic villi associated with hyperglycaemia change the permeability of cell membranes, transferring cells to anaerobic respiration. Metabolic imbalance in the placenta causes the development of diabetic micro-angiopathy in the fetal-placental complex, antenatal hypoxia and negative perinatal outcomes.

The Placental Roots of Intrauterine Growth Restriction Are in the Central and Contractile Regions of the Villous Tree

Background: Intrauterine growth restriction (IUGR) is an obstetric syndrome with a high incidence and severe health burden. The restricted placental growth in IUGR reflects a weight restriction for the placental villous tree. It is unknown whether the whole villous tree or only specific parts of it show restricted growth in IUGR. Clarifying this would have a significant impact on the development of innovative therapeutic approaches for compensating placental dysfunction in IUGR since in the case of uniform growth restriction of the villous tree, IUGR placentas would primarily be smaller than normal placentas. However, if only specific parts of the villous tree are growth restricted, then IUGR placentas would be morphologically, developmentally and, therefore, functionally different from normal placentas. Methods: We investigated ten normal placentas and eleven IUGR placentas with quantitative microscopic techniques (design-based stereology). Using immunohistochemical detection of placental myofibroblasts (γ-sm-actin) and foetoplacental endothelium (CD34), we distinguished between more centrally located villi showing the presence of myofibroblasts (contractile villi; C-villi) and more peripherally located villi showing the absence of myofibroblasts (noncontractile villi; NC-villi). Findings: Compared to normal placentas, IUGR placentas showed significantly reduced mean volumes of C-villi and vessels in C-villi but not of NC-villi. Additional stereologic estimates confirmed the known alterations in the morphology of NC-villi in IUGR. Interpretation: Our results suggest that IUGR placentas are not just smaller but morphologically (and therefore functionally) different from normal placentas. We hypothesize that the reduced volume of C-villi and vessels in C-villi reflects a developmental disturbance in the formation of C-villi (most of them being stem villi). As such, key pathological alterations in IUGR placentas could begin before the formation of intermediate and terminal villi, possibly already in the late first trimester of pregnancy. Funding Statement: Supported by the German Research Council (DFG Fr1245/9-1, to HGF). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The ethics board of Ludwig-Maximilians-University of Munich (LMU Munich) approved all investigations under the numbers 084-11 and 478-12.

Case Series of Placental Mesenchymal Dysplasia with Live Birth

Objective: Placental mesenchymal dysplasia (PDM) is a rare disease, the cause is unknown, some are called mesenchymal stem hyperplasia, and some are called pseudo-vesicular block or vascular malformation. The aim is to report the clinical and pathologic characteristics of three cases of placental mesenchymal dysplasia (PMD). Method: Pathologic and clinical data were retrieved from the electronic medical records. The data were reviewed and summarized by the same pathologist. Results: Maternal age was respective 36 years, 31 years and 33 years. Cesarean section was performed at 39 weeks, 37 weeks and 38 weeks, respectively. The newborns were born with birth weight of 1790, 2370 and 3150 grams, respectively, with placenta weight of 590, 579 and 510 grams respectively. Placenta for pathological examination was performed macroscopically thick-walled vessels. Microscopic observation showed that the part of the stem villus was saclikely dilated, the blood vessels were thickened in the villi, the blood vessel wall was thickened, the villus interstitial was loose, and the mucus was changed. Part of the villus edema and degeneration, no trophoblastic hyperplasia, the final villus structure is normal. Conclusion: The size of the lesions in the Placental mesenchymal dysplasia and the location of the lesion is closely related to the birth weight of the newborn. Detailed histology is necessary for diagnosis and differential diagnosis.

The volume of villi with γ-sm-actin positive perivascular cells correlates with placental weight and thickness

IntroductionThe classification of histologically stained villous cross sections in villous types (terminal, intermediate and stem villi) by stromal peculiarities is known to be observer predicated. Therefore, quantitative histology of villous trees has not become a routine endpoint of studies on the role of the placenta in prenatal programming, as opposed to the gross placental parameters weight and thickness. The classification of villous cross sections in central (stem) and peripheral (terminal) parts based on the presence or absence, respectively, of immunohistochemical detection of myofibroblasts in perivascular position is less observer dependent. We hypothesized that it will, possibly, identify microscopic correlates of placental weight and thickness within the villous tree. Methods50 placentas from clinically normal pregnancies were processed for the present study. Thin villous cross sections, obtained in a systematic random manner, were stained immunohistochemically to detect γ-smooth muscle (sm) actin and to classify them subsequently as part of central or peripheral villous tree. The volume fractions of histological structures visible in villous cross sections (stroma, lumen, endothelium and syncytium) were estimated by design-based stereology. ResultsThe present study reveals a significant correlation of placental weight and thickness with the volume estimate of stroma that have myofibroblasts in perivascular position. DiscussionThe positive linear correlation between the volume of central parts of villous trees and the placental weight and thickness is new. Surprisingly, the volume of more peripheral parts of villous trees, which is the main site of materno-fetal exchange does not correlate with placental weight and thickness.

Expression of the neonatal Fc-receptor in placental-fetal endothelium and in cells of the placental immune system

IntroductionStarting from the second trimester of pregnancy, passive immunity is provided to the human fetus by transplacental transfer of maternal IgG. IgG transfer depends on the neonatal Fc receptor, FcRn. While FcRn localization in the placental syncytiotrophoblast (STB) has been demonstrated unequivocally, FcRn expression in placental-fetal endothelial cells (pFECs), which are part of the materno-fetal barrier, is still unclear. Therefore, this study aimed to elucidate the spatio-specific expression pattern of FcRn in placental tissue. MethodsFcRn expression was investigated by western blotting in term placentas and in isolated human placental arterial and venous endothelial cells (HPAEC, HPVEC) using a validated affinity-purified polyclonal anti-peptide antibody against the cytoplasmic tail of FcRn α-chain. In situ localization of FcRn and IgG was studied by immunofluorescence microscopy on tissue sections of healthy term placentas. ResultsFcRn expression was demonstrated in placental vasculature particularly, in HPAEC, and HPVEC. FcRn was localized in cytokeratin 7+ STB and in CD31+ pFECs in terminal as well as stem villi in situ. Additionally, CD68+ placental macrophages exhibited FcRn expression in situ. Endogenous IgG partially co-localized with FcRn in STB, pFECs, and in placental macrophages. DiscussionPlacental FcRn expression in endothelial cells and macrophages is analogous to the expression pattern in other organs. FcRn expression in pFECs suggests an involvement of FcRn in IgG transcytosis and/or participation in recycling/salvaging of maternal IgG present in the fetal circulation. FcRn expression in placental macrophages may account for recycling of monomeric IgG and/or processing and presentation of immune complexes.

Biochemical Characterization of 20α-Hydroxysteroid Dehydrogenase

In this review, we have tried to summarize the evidence and molecular characterization indicating that 20α-hydroxysteroid dehydrogenase (20α-HSD) is a group of the aldo-keto reductase (AKR) family, and it plays roles in the modulation and regulation of steroid hormones. This enzyme plays a critical role in the regulation of luteal function in female mammals. We have studied the molecular expression and regulation of 20α-HSD in cows, pigs, deer, and monkeys. The specific antibody against bovine 20α-HSD was generated in a rabbit immunized with the purified recombinant protein. The mRNA expression levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. The mRNA was also specifically detected in the placental and ovarian tissues during pregnancy. The 20α-HSD protein was intensively localized in the large luteal cells and placental cytotrophoblast villus, glandular epithelial cells of the endometrium, syncytiotrophoblast of the placenta, the isthmus cells of the oviduct, and the basal part of the primary chorionic villi and chorionic stem villus of the placenta and large luteal cells of the CL in many mammalian species. Further studies are needed to determine the functional significance of the 20α- HSD molecule during ovulation, pregnancy, and parturition. This article will review how fundamental information of these enzymes can be exploited for a better understanding of the reproductive organs during ovulation and pregnancy.