Placental Morphological Changes Research Articles

Morphological evaluation of the feline placenta correlates with gene expression of vascular growth factors and receptors†.

Placental angiogenesis is critical for normal development. Angiogenic factors and their receptors are key regulators of this process. Dysregulated placental vascular development is associated with pregnancy complications. Despite their importance, vascular growth factor expression has not been thoroughly correlated with placental morphologic development across gestation in cats. We postulate that changes in placental vessel morphology can be appreciated as consequences of dynamic expression of angiogenic signaling agents. Here, we characterized changes in placental morphology alongside expression analysis of angiogenic factor splice variants and receptors throughout pregnancy in domestic shorthair cats. We observed increased vascular and lamellar density in the lamellar zone during mid-pregnancy. Immunohistochemical analysis localized the vascular endothelial growth factor A (VEGF-A) receptor KDR to endothelial cells of the maternal and fetal microvasculatures. PlGF and its principal receptor Flt-1 were localized to the trophoblasts and fetal vasculature. VEGF-A was found in trophoblast cells and associated with endothelial cells. We detected expression of two Plgf splice variants and four Vegf-a variants. Quantitative real-time polymerase chain reaction analysis showed upregulation of mRNAs encoding pan Vegf-a and all Vegf-a splice forms at gestational days 30-35. Vegf-A showed a marked relative increase in expression during mid-pregnancy, consistent with the pro-angiogenic changes seen in the lamellar zone at days 30-35. Flt-1 was upregulated during late pregnancy. Plgf variants showed stable expression during the first two-thirds of pregnancy, followed by a marked increase toward term. These findings revealed specific spatiotemporal expression patterns of VEGF-A family members consistent with pivotal roles during normal placental development.

Placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity and healthy pregnancies.

Malaria and preeclampsia are leading causes of maternal morbidity and mortality in sub-Saharan Africa. They contribute significantly to poor perinatal outcomes like low neonatal weight by causing considerable placental morphological changes that impair placental function. Previous studies have described the effects of either condition on the placental structure but the structure of the placenta in malaria-preeclampsia comorbidity is largely understudied despite its high burden. This study aimed to compare the placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity versus those with healthy pregnancies. We conducted a retrospective cohort study among 24 women with malaria-preeclampsia comorbidity and 24 women with healthy pregnancies at a County Hospital in Western Kenya. Neonatal weights, gross and histo-morphometric placental characteristics were compared among the two groups. There was a significant reduction in neonatal weights (P<0.001), placental weights (P = 0.028), cord length (P<0.001), and cord diameter (P<0.001) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. There was also a significant reduction in villous maturity (P = 0.016) and villous volume density (P = 0.012) with increased villous vascularity (P<0.007) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. Placental villous maturity and villous volume density are significantly reduced in patients with malaria-preeclampsia comorbidity with a compensatory increase in villous vascularity. This leads to impaired placental function that contributes to lower neonatal weights.

Association of maternal thyroid peroxidase antibody during pregnancy with placental morphology and inflammatory and oxidative stress responses.

Studies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines. Based on Ma'anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators. Totally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-α, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-α, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity. There may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses.

Maternal obesity-related placental dysfunction: From peri-conception to late gestation

Obesity is a global epidemic with alarmingly high prevalence rates worldwide. The increasing incidence of obesity among reproductive age women, which progresses to obesity in pregnancy is of particular concern. A successful pregnancy is dependent on the balanced interaction between maternal cardiometabolic function, genetic predisposition, and optimal placental development. Maternal obesity, both pre-pregnancy and gestational, has been associated with adverse outcomes including poor fetal development, stillbirth, preterm birth, and metabolic complications later in life. To gain a more comprehensive understanding of the mechanistic interplay of key mediators of obesity-associated placental dysfunction and adverse pregnancy outcomes, we conducted a review of 24 studies that investigated placental dysfunction and maternal obesity retrieved from MEDLINE, LILACS and EMBASE. The findings demonstrate that maternal obesity is a well-established risk factor for poor placental function. Pre-pregnancy obesity alters the placental transcriptome. Maternal obesity during gestation induces changes in placental morphology, dysregulated placental metabolism, inflammation and oxidative state, as well as endothelial dysfunction. There is also clear evidence that maternal obesity is associated with altered placental angiogenesis/vascularisation which increases the risk of early-onset preeclampsia. Studies show a link between maternal obesity and increased placental vascular disorders, placental weight, placental volume and birth weight. These obesity-related placental disorders are often associated with insulin resistance and gestational diabetes mellitus.

Histomorphometric Survey of Placentas of HIV-positive Mothers in Relation to their Clinical Stage in a Teaching Hospital in Uyo, South-South Nigeria.

HIV infection in pregnancy affects the mother, her placenta, and fetus resulting in perinatal/maternal morbidity and mortality. Studies show that HIV-positive mothers have several placental morphological changes. This study aimed to describe the histomorphometric parameters/lesions of placentas of HIV-positive mothers in Uyo, Akwa Ibom State, Nigeria. A prospective cross-sectional hospital-based analytical study was conducted at the departments of Obstetrics and Gynecology, and Histopathology, University of Uyo Teaching Hospital, Nigeria from December 2015 to May 2016. We studied 144 pregnant mothers (48 HIV-positive as the test group vs. 96 HIV-negative as controls). Their placentas (fetal membrane, umbilical cord, and placental disk) were collected post-delivery and evaluated (grossly/microscopically) to determine the range of histomorphometric placental parameters/lesions. Relevant obstetric data were obtained from their case notes. The test group delivered more through cesarean section than the control group (52.1% vs. 31.3%), with mean birth weights of 2.8±0.7 and 3.1±0.6 kg (p = 0.004). The mean placental weights were 57±190.1 and 664.6±167.4 g (p = 0.003), with mean placenta-birth weight ratio of 20.1±4.8 and 20.5±4.57% (p = 0.33). The test groups placental fetal membranes, umbilical cords, and disks mainly displayed acute chorioamnionitis (47.9%), acute umbilical phlebitis (14.6%), and villous vasculopathy (33.3%). The test group had a higher stage/grade of placental inflammation than the control group. In the test group, two stage 4 HIV disease state cases presented with the most severe form of placental inflammatory lesions. The commonest placental histomorphometric parameters/lesions were acute chorioamnionitis, acute umbilical phlebitis, and acute intervillositis. There was no significant association between HIV/AIDS disease stage with the most severe forms of placental inflammatory lesions.

Comparative evaluation of placental elasticity in normal pregnancy and pregnancy-induced hypertension and its association with uterine artery pulsatility index and fetal outcome

Background: Pregnancy-induced hypertension (PIH) is associated with significant maternal as well as fetal morbidity and untreated cases may be associated with poor pregnancy outcomes. It brings about various histological and morphological changes in the placenta such as infarcts, fibrosis, and calcification thereby affecting the well-being of fetus. Detection of it at an early stage is important from the point of view of management as early intervention is associated with improved maternal and fetal outcome. Shear wave elastography (SWE) of placenta is a non-invasive investigation that can detect changes in placental elasticity during the pregnancy. Aims and Objectives: The aim of the study was to assess and compare the difference in values of placental elasticity in normal pregnancy and in clinically diagnosed cases of PIH and to study its association with uterine artery-pulsatility index (UtA-PI) and fetal outcome. Materials and Methods: This was a prospective and observational study in which pregnant females with gestational age of 20–34 weeks who were referred to radiology department for routine sonography including the clinically diagnosed pregnancies with PIH were included on the basis of a predefined inclusion and exclusion criteria. A total of 106 individuals were included in the study, B-mode sonography, uterine artery Doppler, and placental SWE were performed in all these patients. All these pregnancies were followed up for the fetal outcome. Results: The mean gestational age of the studied cases was found to be 26.51±4.415 weeks. Higher SWE values were found, as compared to the normal pregnancies, in pregnancies complicated by PIH and the difference was found to be statistically highly significant (P&lt;0.001). Placental SWE showed a strong association with UtA-PI and fetal outcome. Incidence of adverse fetal outcome such as preterm deliveries, intrauterine death, stillbirths, and small for gestational age babies was more commonly seen in PIH group and the difference was statistically significant (P&lt;0.005). Incidence of birth asphyxia (as determined by low APGAR score) and neonatal intensive care unit admissions was more in neonates born to patients with PIH as compared to those in healthy women and the difference was statistically significant (P&lt;0.005). Conclusion: SWE has the potency to detect the changes in placental morphology and can help with diagnosis of pregnancies complicated with PIH. It does have a synergistic role to play alongside the uterine artery Doppler and clinical parameters to predict the pregnancies with PIH.

Does gestational diabetes mellitus influence the morphological characteristics of the placenta?

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance, with a decrease in insulin sensitivity during pregnancy, with recognition in the second or third trimester of pregnancy and disappearing after delivery. This mini-review is to provide a broad view of some recent studies that investigated the placental morphology in cases of maternal diagnosis of gestational diabetes. A literature search was carried out in PubMed, Medline, Google Scholar data sources, verifying the morphological characteristics of the placenta in situations of diagnosis of gestational diabetes, through prospective and observational studies, with the key terms “gestational diabetes”, “placenta” and ‘morphological”. We show, in table format, the studies carried out between 2015 and 2020 with the main placental morphological changes that reflect the condition of pregnant women with diabetes mellitus, the most considered in the literature, increase in placental weight and thickness. It was evident that there are still few studies on placental changes, requiring the encouragement of scientific productions on the approach. In conclusion, understanding the mechanism of placental development allows the assessment of changes when pregnant women are diagnosed with GDM, taking into account therapeutic strategies that can intervene in glycemic and metabolic control, in order to ensure maternal-fetal health.

T2*-weighted placental magnetic resonance imaging: a biomarker of placental dysfunction in small-for-gestational-age pregnancies

The antenatal identification of placental dysfunction in small-for-gestational-age fetuses with normal fetal Doppler flows remains an obstetrical challenge. In a significant fraction of such pregnancies, placental dysfunction is revealed by clinical manifestations such as preeclampsia, preterm delivery, or severe small-for-gestational-age at birth or by abnormal findings in the postnatal placental histologic examination. Therefore, new methods to identify placental function directly in pregnancy at the time of small-for-gestational-age diagnosis is highly needed. T2*-weighted placental magnetic resonance imaging is sensitive to changes in placental morphology and oxygenation and is thereby related to placental function. Previous studies have demonstrated that pregnancies complicated by low birthweight and preeclampsia are characterized by low placental T2* values. However, the specific performance of placental T2* in the prediction of placenta-related outcomes in small-for-gestational-age pregnancies with normal fetal Doppler flows remains to be explored. In small-for-gestational-age pregnancies with normal fetal Doppler flows, we aimed to evaluate T2*-weighted placental magnetic resonance imaging as an antenatal biomarker of placental dysfunction. In addition, we aimed to investigate the correlation between placental T2* and Doppler flow measurements of fetal and uterine arteries at the time of magnetic resonance imaging. In this prospective cohort study, the inclusion criterion was suspected small-for-gestational-age (ultrasound estimated fetal weight Z-score ≤-2.0 [2.3rd centile]) with normal fetal Doppler flows (middle cerebral artery pulsatility index Z-score > -2.0 and umbilical artery pulsatility index Z-score <2.0). The T2*-weighted placental magnetic resonance imaging scan was performed at inclusion in a 1.5 T system. The outcomes was placental dysfunction at birth defined by low birthweight (Z-score ≤-2.0), preeclampsia, preterm delivery (gestational age<37 weeks), or abnormal placental histologic examination such as placental vascular malperfusion according to the Amsterdam Consensus Statement. We included 92 pregnancies at 26+5 to 39+6 weeks gestation. The median time interval between the magnetic resonance imaging scan and birth was 4.6 weeks (interquartile range, 2.7-7.8 weeks). At birth, 55% (51/92) of pregnancies revealed at least 1 sign of placental dysfunction; 49% (40/81) had abnormal placental histologic examination, 29% (27/92) were born with low birthweight, 13% (12/92) were delivered preterm, and 7% (6/92) had preeclampsia. When adjusted for gestational age at magnetic resonance imaging, the placental T2* Z-score was a significant predictor of abnormal placental histologic examination (area under the curve, 0.73; P=.001), small-for-gestational-age at birth (area under the curve, 0.63; P=.030), preeclampsia (area under the curve, 0.88; P=.005), and preterm delivery (area under the curve, 0.81; P=.001). The placental T2* was reduced in pregnancies with a combination of clinical manifestations and abnormal placental histologic examination (T2* Z-score=-1.52±1.35 [mean±standard deviation]; P=.0001) and in clinically uneventful pregnancies with abnormal placental histologic examination (T2* Z-score=-0.79±0.97; P=.045). At the time of magnetic resonance imaging, the placental T2* Z-score showed a significant linear correlation with the uterine artery pulsatility index Z-scores (r=-0.24; P=.016) and the middle cerebral artery pulsatility index Z-scores (r=0.29; P=.017) but not with the umbilical artery pulsatility index Z-scores (r=0.18; P=.17) and the cerebroplacental ratio (r=0.03; P=.77). This study indicates that placental dysfunction is frequent in small-for-gestational-age fetuses with normal fetal Doppler flows. In this cohort, T2*-weighted placental magnetic resonance imaging is a sensitive biomarker of placental dysfunction regardless of the clinical manifestations. This finding supports a paradigm shift in the conception of placental dysfunction that may cover a wide spectrum of clinical and subclinical manifestations.

Does COVID-19 cause pre-eclampsia?

Does COVID-19 cause pre-eclampsia?

Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males.

Epigenetic mechanisms of paternal inheritance are an emerging area of interest in our efforts to understand fetal alcohol spectrum disorders. In rodent models examining maternal alcohol exposures, different maternal genetic backgrounds protect or sensitize offspring to alcohol‐induced teratogenesis. However, whether maternal background can mitigate sperm‐inherited alterations in developmental programming and modify the penetrance of growth defects induced by preconception paternal alcohol exposures remains unaddressed. In our previous studies examining pure C57Bl/6J crosses, the offspring of alcohol‐exposed sires exhibited fetal growth restriction, enlarged placentas, and decreased placental efficiency. Here, we find that in contrast to our previous studies, the F1 offspring of alcohol‐exposed C57Bl/6J sires and CD‐1 dams do not exhibit fetal growth restriction, with male fetuses developing smaller placentas and increased placental efficiencies. However, in these hybrid offspring, preconception paternal alcohol exposure induces sex‐specific changes in placental morphology. Specifically, the female offspring of alcohol‐exposed sires displayed structural changes in the junctional and labyrinth zones, along with increased placental glycogen content. These changes in placental organization are accompanied by female‐specific alterations in the expression of imprinted genes Cdkn1c and H19. Although male placentae do not display overt changes in placental histology, using RNA‐sequencing, we identified programmed alterations in genes regulating oxidative phosphorylation, mitochondrial function, and Sirtuin signaling. Collectively, our data reveal that preconception paternal alcohol exposure transmits a stressor to developing offspring, that males and females exhibit distinct patterns of placental adaptation, and that maternal genetic background can modulate the effects of paternal alcohol exposure.

Efficacy of vitamin E in protection against methotrexate induced placental injury in albino rats

Methotrexate (MXT) is a chemotherapeutic drug that has been used in a wide range of clinical practices. Unfortunately, the administration of MXT during pregnancy may induce abortion, fetal deformities, and intrauterine growth retardation. Vitamin E is an antioxidant agent that can ameliorate free radical damage. The current work aimed to shed more light on the possible protective effect of vitamin E against MXT induced placental toxicity and to determine the possible mechanisms; biochemically, histologically, and immunohistochemically. Four groups were used: control pregnant, Vitamin E (VIT E) pregnant, Methotrexate (MXT) pregnant, and Vitamin E Methotrexate (VIT E-MXT) pregnant. The placental tissues were processed for light, immunohistochemical, and electron microscopic study. Other samples were obtained for biochemical study; the placental oxidant/antioxidant status was evaluated. The results showed that MXT caused various placental morphological changes in the form of distorted chorionic projection with an accumulation of hemosiderin granules in the trophoblastic cells. Maternal blood vessels showed a homogenous acidophilic material Edema of the extra-embryonic fetal membranes was noticed. A significant decreased in placental weight as well as increase in the oxidative and inflammatory markers were detected. Increased COX2 and decreased eNOS expressions were observed in the MXT group if compared to the control group. VIT E significantly restored the normal histological and immunohistochemical appearance, placental weight, and oxidant/antioxidant balance. It could be concluded the biochemical, morphological, and morphometric findings suggested that vitamin E coadministration is promising in attenuating the placental toxic effect of methotrexate. In this study, VIT E decreased the inflammatory and oxidative stress effect of methotrexate on the placental tissue by enhancing the level of eNOS.

Maternal Hyperglycemia Induces Changes in Gene Expression and Morphology in Mouse Placentas.

Pregestational diabetes complicates one million pregnancies in the United States and is associated with placental dysfunction. Placental dysfunction can manifest as stillbirth, spontaneous abortions, fetal growth restriction, and preeclampsia in the mother. However, the underlying mechanisms of placental dysfunction are not well understood. We hypothesize that maternal hyperglycemia disrupts cellular processes important for normal vascular development and function. Hyperglycemia, defined as a non-fasting glucose concentration of >250 mg/dL was induced in eight-week-old female CD1 mice by injecting a one-time intraperitoneal dose of 150mg/kg streptozotocin. Control mice received an equal volume of normal saline. Hyperglycemic and control females were mated with CD-1 males. At Embryonic Day 17.5, the pregnant mice were euthanized. Sixty-eight placentas were harvested from the six euglycemic dams and twenty-six placentas were harvested from three hyperglycemic dams. RNA was extracted from homogenized placental tissue (N=12/group; 2-4 placentas per litter of each group). Total RNA was prepared and sequenced. Differentially expressed genes that were >2-fold change was considered significant. Placentas (9-20/group) were fixed in paraffin wax and sectioned at 6 μm. Cross-sectional areas of placental zones were evaluated using slides stained for hematoxylin and eosin, glycogen, collagen, proliferation and apoptosis. Quantification of staining intensity and percent positive nuclei was done using Leica Image Hub Data software. Data were compared between the control and experimental group using t-tests. Values of p < 0.05 were considered to be statistically significant. The average maternal blood glucose concentrations for control and diabetic dams were 112+/-24 and 473+/-47 respectively (p<0.0001). A higher rate of resorptions was noted in the hyperglycemia exposed placentas compared to euglycemic exposed placentas (24% vs 7%; p=0.04). A total of 24 RNA libraries (12/group) were prepared. Placentas from hyperglycemic pregnancies exhibited 1374 differentially expressed genes (DEGs). The 10 most significantly differentially expressed genes are Filip 1, Prom 2, Fam 78a, Pde4d, Pou3f1, Kcnk5, Dusp4, Cxcr4, Slc6a4 and D430019H16Rik. Their corresponding biologic functions are related to chemotaxis, ossification, cellular and vascular development. Histologically, we found that hyperglycemia exposed placentas demonstrated increased proliferation, apoptosis, and glycogen content and decreased collagen deposition. There was a higher rate of resorptions in the pregnancies of hyperglycemic dams. Pregestational diabetes resulted in significant changes in placental morphology, including increased glycogen content in the spongiotrophoblast, decreased collagen deposition, increased apoptosis and proliferation in the junction zone. Maternal diabetes causes widespread disruption in multiple cellular processes important for normal vascular development and sets the platform for placenta dysfunction.

Study on Histomorphological Findings in Placenta in Cases of Pregnancy Induced Hypertension

Introduction: PIH is a common condition associated with changes in placenta. It leads to increased perinatal mortality. The present study was conducted to assess the morphological and histopathological changes in placenta in cases of pregnancy induced hypertension. Subjects and Methods: The present comparative study included 49 cases of PIH and 49 normotensive mothers. Clinical details and placental morphology were noted. Results: That the two groups are similar with no significant difference. Placental weight and diameter were similar in PIH and control groups (p&gt;0.05). However, placental thickness and number of cotyledons were greater in PIH group (p=0.00) while placental volume was lower with significant difference (p=0.01). PIH group showed greater proportion of infarction, calcification, hyalinised area per 10 lpf and intervillous haemorrhage (p=0.00). Conclusion: PIH leads to gross and microscopic changes in placental morphology.

Morphological Study of Placenta in Low Birth Weight Infants

Objective: To study placental morphological changes in low birth weight neonates Material and Method: This prospective case-control study was carried out on 100 cases at Muzaffarnagar Medical College, Muzaffarnagar. Placentas of Low Birth Weight term babies were collected from department of gynaecology and obstetrics during the period from March 2016 to May 2017.Placental morphological changes were studied. Conclusion: The mean placental weight, thickness and diameter for the case group was lower than the control group. Also the mean placental thickness and diameter of case group was found to be lower than in control group. Highest placental weight in both cases and control was found in 18-22 years age group mothers. However highest neonatal weight in both cases and control was found in 28-32 years age group mothers

Maternal malnutrition impacts placental morphology and transporter expression: an origin for poor offspring growth

The placenta promotes fetal growth through nutrient transfer and selective barrier systems. An optimally developed placenta can adapt to changes in the pregnancy environment, buffering the fetus from adverse exposures. We hypothesized that the placenta adapts differently to suboptimal maternal diets, evidenced by changes in placental morphology, developmental markers and key transport systems. Mice were fed a control diet (CON) during pregnancy, undernourished (UN) by 30% of control intake from gestational day (GD) 5.5–18.5 or fed 60% high-fat diet (HF) 8 weeks before and during pregnancy. At GD18.5, placental morphometry, development and transport were assessed. Junctional and labyrinthine areas of UN and HF placentae were smaller than CON by >10%. Fetal blood space area and fetal blood space:fetal weight ratios were reduced in HF vs. CON and UN. Trophoblast giant cell marker Ctsq mRNA expression was lower in UN vs. HF, and expression of glycogen cell markers Cx31.1 and Pcdh12 was lower in HF vs. UN. Efflux transporter Abcb1a mRNA expression was lower in HF vs. UN, and Abcg2 expression was lower in UN vs. HF. mRNA expression of fatty acid binding protein Fabppm was higher in UN vs. CON and HF. mRNA and protein levels of the lipid transporter FAT/CD36 were lower in UN, and FATP4 protein levels were lower in HF vs. UN. UN placentae appear less mature with aberrant transport, whereas HF placentae adapt to excessive nutrient supply. Understanding placental adaptations to common nutritional adversities may reveal mechanisms underlying the developmental origins of later disease.

Changes in Placental Morphology and their Association with Embryonic Skin Development

Abstract Histogenesis and organogenesis in mammals normally transpires in a hypoxic environment. Oxygen diffusing capacity is dependent on diffusion distance, which may vary with the thickness of placental barrier and with the level of tissue vascularity. Since the epidermis is avascular, its development fully depends on dermal blood vessels. Despite the large number of studies focusing on uteroplacental circulation and embryogenesis, it is clear that the current knowledge of how placental changes in pregnancy contribute to skin development is incomplete. The aim of this study was to evaluate the association between structural changes in the placental barrier and development of the integumentary system, with special reference to dermal angiogenesis. The study included specimens of six embryos and ten foetuses from 5 to 24 developmental weeks, and 21 specimens of placental tissue 6–40 weeks gestational age. The panel of antibodies used was S- 100, SMA, CD31, CD34, AE1/AE3 (PCKT), CKRT7, CD 56 and hCG. During the first trimester, maternal blood flow to the placenta appears to be initially restricted by trophoblast plugs. Natural killer cells appear in great abundance in subendothelium of decidual blood vessels, potentially stimulating extensive angiogenesis. By the end of the first trimester, new capillary beds organise to supply the developing epidermal derivatives. During the second trimester, the placental barrier becomes progressively thinner, and uteroplacental circulation is established due to dissolution of endovascular trophoblast plugs. Progression of the formation of skin appendages, hypodermal adipose tissue, demarcation of papillary and reticular dermis, and keratinisation of interfollicular epidermis in the second trimester strongly accompanies the dermal angiogenesis and placental maturation.

Quantification of placental change in mouse models of preeclampsia using magnetic resonance microscopy.

Abnormal development of the placenta is postulated to be central to the aetiology of preeclampsia. This study investigates changes in placental histopathology in mouse models of preeclampsia compared to the morphology using magnetic resonance microscopy (MRM) (11.7 T) of intact ex vivo tissue followed by 3D analysis of the image data. Here, C57BL/6JArc pregnant mice were subject to either normal pregnancy (n=3), or to one of two experimental models of preeclampsia; TNF-α infusion (n=3) or reduced uterine perfusion pressure (RUPP) (n=3). Placental tissue was collected at gestational day (gd) 17, fixed in formalin and incubated with Magnavist™ contrast agent, and high resolution images (50 μm × 50 μm × 50 μm voxels) obtained by magnetic resonance imaging at 11.74 T. Visual segmentation into placental subregions and three dimensional (3D) reconstruction followed by volume analysis was performed with Amira™ 3D analysis software. The significance of differences between treatment groups in total and regional volumes was assessed. In a single placenta the volumes measure by standard histology were compared. Three placentas from each animal were imaged, segmented into anatomical regions and 3D reconstructions generated. Total placental volume, labyrinth and decidual volume were not significantly different between groups. The junctional zone volume was found to be significantly larger in the RUPP animals (18.5±1.5 mm3) compared to TNF-α infused animals (15.8±1.5) or control animals (15.0±0.7, P<0.01). However, the decidual/junctional zone volume was smaller in the TNF-a compared to control animals (P<0.05). Placental structural change in experimental models of preeclampsia is able to be visualized and quantified using MRM and 3-D analysis. These techniques could prove to be a powerful tool in examining changes in placental morphology.

Advanced maternal age may impact placental morphology in IVF pregnancies

Advanced maternal age (35 years and older) is associated with an increasing incidence of obstetric complications, such as preeclampsia and stillbirth. The changes in placental morphology with increasing age as a potential contributor to these outcomes is not currently well understood.

Decrease in Sphingomyelin (d18:1/16:0) in Stem Villi and Phosphatidylcholine (16:0/20:4) in Terminal Villi of Human Term Placentas with Pathohistological Maternal Malperfusion.

Placental villi play pivotal roles in feto-maternal transportation and phospholipids constitute a major part of the villous membrane. We have been developing and optimizing an imaging system based on a matrix-assisted laser desorption/ionization (MALDI)-based mass spectrometer, which provides clear two-dimensional molecular distribution patterns using highly sensitive mass spectrometry from mixtures of ions generated on tissue surfaces. We recently applied this technology to normal human uncomplicated term placentas and detected the specific distribution of sphingomyelin (SM) (d18:1/16:0) in stem villi and phosphatidylcholine (PC) (16:0/20:4) in terminal villi. In the present study, we applied this technology to nine placentas with maternal or fetal complications, and determined whether a relationship existed between these specific distribution patterns of phospholipid molecules and the six representative pathological findings of placentas, i.e., villitis of unknown etiology (VUE), thrombus, atherosis, chorioamnionitis (CAM), immature terminal villi, and multiple branched terminal villi. In two placentas with the first and second largest total number of positive pathological findings, i.e., five and three positive findings, the specific distribution of SM (d18:1/16:0) in stem villi and PC (16:0/20:4) in terminal villi disappeared. The common pathological findings in these two placentas were atherosis, immature terminal villi, and multiple branched terminal villi, suggesting the possible involvement of the underperfusion of maternal blood into the intervillous space. On the other hand, the number of pathological findings were two or less in the seven other placentas, in which no specific relationships were observed between the differential expression patterns of these two phospholipids in stem and terminal villi and the pathological findings of the placentas; however, the specific distribution pattern of SM (d18:1/16:0) in stem villi disappeared in four placentas, while that of PC (16:0/20:4) in terminal villi was preserved. These results suggested that the absence of the specific distribution of PC (16:0/20:4) in terminal villi, possibly in combination with the absence of SM (d18:1/16:0) in stem villi, was linked to placental morphological changes in response to maternal underperfusion of the placenta.

Heat shock transcription factor 1 expression is spatially distributed and selectively down-regulated in the human placenta during labour

Heat shock transcription factor 1 expression is spatially distributed and selectively down-regulated in the human placenta during labour