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Romanian Journal of Morphology and... 2023Early-onset fetal growth restriction (FGR), an identifiable variant of FGR, exhibits divergences in its severity, management, and placental pathologies when juxtaposed...
BACKGROUND
Early-onset fetal growth restriction (FGR), an identifiable variant of FGR, exhibits divergences in its severity, management, and placental pathologies when juxtaposed with late-onset FGR. The objective of this cross-sectional investigation was to scrutinize placental pathologies in pregnancies afflicted by early-onset FGR, emphasizing a comparative analysis between cohorts with and without preeclampsia (PE).
PATIENTS, MATERIALS AND METHODS
The study encompassed a cohort of 85 expectant mothers who received a diagnosis of early-onset FGR. Rigorous histopathological (HP) and immunohistochemical (IHC) assessments were conducted on the placentas. Comparative analyses were performed, distinguishing between individuals diagnosed with both PE and early-onset FGR, and those presenting normotensive early-onset FGR.
RESULTS
HP analysis unveiled a multitude of shared placental lesions, encompassing retroplacental hemorrhage, expedited villous maturation, infarctions, and calcification-associated fibrin deposits. IHC investigations displayed affirmative immunoreactivity for anti-hypoxia-inducible factor (HIF) and anti-vascular endothelial growth factor (VEGF) antibodies within the placental infarcted villitis. Moreover, noteworthy variances in placental measurements and distinctive lesions were discerned when comparing the PE and early-onset FGR cohort with the normotensive group.
CONCLUSIONS
Maternal malperfusion emerged as a pivotal determinant linked to placental lesions in pregnancies affected by early-onset FGR. Remarkably, the occurrence of infarctions, specifically delayed infarctions, exhibited a noteworthy correlation with PE. These findings accentuate the significance of pursuing additional research endeavors aimed at unraveling the intricate mechanisms governing maternal malperfusion and its consequential influence on placental health in the context of early-onset FGR, with particular attention to the interplay with PE.
Topics: Pregnancy; Female; Humans; Placenta; Fetal Growth Retardation; Cross-Sectional Studies; Placenta Diseases; Pre-Eclampsia; Infarction
PubMed: 37518879
DOI: 10.47162/RJME.64.2.12 -
Obstetrics and Gynecology Feb 2014To compare placental lesions for stillbirth cases and live birth controls in a population-based study. (Comparative Study)
Comparative Study
OBJECTIVE
To compare placental lesions for stillbirth cases and live birth controls in a population-based study.
METHODS
Pathologic examinations were performed on placentas from singleton pregnancies using a standard protocol. Data were analyzed overall and within gestational age groups at delivery.
RESULTS
Placentas from 518 stillbirths and 1,200 live births were studied. Single umbilical artery was present in 7.7% of stillbirths and 1.7% of live births, velamentous cord insertion was present in 5% of stillbirths and 1.1% of live births, diffuse terminal villous immaturity was present in 10.3% of stillbirths and 2.3% of live births, inflammation (eg, acute chorioamnionitis of placental membranes) was present in 30.4% of stillbirths and 12% of live births, vascular degenerative changes in chorionic plate were present in 55.7% of stillbirths and 0.5% of live births, retroplacental hematoma was present in 23.8% of stillbirths and 4.2% of live births, intraparenchymal thrombi was present in 19.7% of stillbirths and 13.3% of live births, parenchymal infarction was present in 10.9% of stillbirths and 4.4% of live births, fibrin deposition was present in 9.2% of stillbirths and 1.5% of live births, fetal vascular thrombi was present in 23% of stillbirths and 7% of live births, avascular villi was present in 7.6% of stillbirths and 2.0% of live births, and hydrops was present in 6.4% of stillbirths and 1.0% of live births. Among stillbirths, inflammation and retroplacental hematoma were more common in placentas from early deliveries, whereas thrombotic lesions were more common in later gestation. Inflammatory lesions were especially common in early live births.
CONCLUSIONS
Placental lesions were highly associated with stillbirth compared with live births. All lesions associated with stillbirth were found in live births but often with variations by gestational age at delivery. Knowledge of lesion prevalence within gestational age groups in both stillbirths and live birth controls contributes to an understanding of the association between placental abnormality and stillbirth.
LEVEL OF EVIDENCE
II.
Topics: Adult; Chorioamnionitis; Chorionic Villi; Female; Fetal Death; Gestational Age; Humans; Live Birth; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Single Umbilical Artery; Stillbirth
PubMed: 24402599
DOI: 10.1097/AOG.0000000000000100 -
Reproductive Medicine (Basel,... Mar 2022Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction,...
Characteristics of maternal vascular malperfusion (MVM) are frequently observed in placentas from pregnancies impacted by preeclampsia, intrauterine growth restriction, preterm labor, and intrauterine fetal demise. We sought to evaluate the associations of features of MVM with subclinical measures of cardiovascular health and coagulation potential in healthy young women. Sixty-three healthy young women were recruited and assessed prior to pregnancy on cycle day 9 ± 4, at gestational age 90 ± 6 of early pregnancy, and gestational age 216 ± 5 of late pregnancy. Women were assessed for plasma volume, blood pressure, response to volume loading, cardiac output, and uterine hemodynamics. Platelet-poor plasma was collected to assess thrombin generation on a subset of 33 women at all time points. Following delivery, placentas were collected and analyzed for evidence of MVM. Thrombin generation (TG) was evaluated in the presence of tissue factor (TF) with and without recombinant soluble thrombomodulin (TM). For each, we compared TG lagtime, peak level, and endogenous thrombin potential (ETP). Comparisons were made between dichotomized presence and absence of each individual feature of MVM and cardiovascular and coagulation features. Mean ± standard deviation are presented. Women were 31 ± 4 years of age, body mass index of 24 ± 5 kg/m, 86% white race, and 80% nulliparous. MVM occurred in 70% of placentas, with infarcts and agglutination (44%), decidual arteriopathy (40%), accelerated villous maturation (32%), placental hypoplasia (29%), and distal villous hypoplasia (17%) documented. Decidual arteriopathy and distal villous hypoplasia were associated with prepregnancy maternal physiology, including decreased plasma volume and subclinical cardiovascular variations. All assessed MVM characteristics had identifiable early pregnancy physiologic characteristics consistent with altered cardiovascular function and decreased uterine response to pregnancy when compared with women who did and did not develop MVM. Accelerated villous maturation was the only MVM feature to differ by thrombin generation parameters in early pregnancy. Thrombin generation potential and blood pressure were elevated in late pregnancy in women who developed decidual arteriopathy. Prepregnancy health status and adaptation to pregnancy play important roles in pregnancy outcomes. Both cardiovascular health and thrombin generation potential may influence early placentation. Longitudinal assessment of subclinical maternal factors may allow for better understanding of the etiologies of MVM lesions, as well as allow for identification of a timeline of the origins of placental pathologies.
PubMed: 36923963
DOI: 10.3390/reprodmed3010006 -
American Journal of Obstetrics &... Jan 2022We presented the case of stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marble appearance and a...
We presented the case of stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marble appearance and a focal hemorrhagic area. Multiple areas of hemorrhagic or ischemic necrosis with central and peripheral villous infarctions and thrombosis of several maternal and fetal vessels with luminal fibrin and platelet deposition were observed. All lesions seemed to be synchronous. Virus particles were identified within the cytoplasm of endothelial cells using electron microscopy, whereas SARS-CoV-2 RNA was detected in the placental tissue using real-time reverse transcription-polymerase chain reaction. Here, fetal vascular malperfusion was associated with infection; in fact, electron microscopy images showed that marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries. Furthermore, we confirmed that syncytiotrophoblast is the major target cell type for SARS-CoV-2 infection of the placenta. In conclusion, the possible consequences of the action of the placentotropic SARS-CoV-2 included the occurrence of vertical transmission, as reported in the literature, and/or stillbirth: the latter possibility may be triggered by a hampered maternal and/or fetal perfusion of the placenta. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance.
Topics: COVID-19; Capillaries; Endothelial Cells; Female; Humans; Placenta; Pregnancy; RNA, Viral; SARS-CoV-2; Stillbirth
PubMed: 34700024
DOI: 10.1016/j.ajogmf.2021.100523 -
Stem Cell Research & Therapy Jan 2021The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown.
Myocardial repair of bioengineered cardiac patches with decellularized placental scaffold and human-induced pluripotent stem cells in a rat model of myocardial infarction.
BACKGROUND
The creation of a bioengineered cardiac patch (BCP) is a potential novel strategy for myocardial repair. Nevertheless, the ideal scaffold for BCP is unknown.
OBJECTIVE
We investigated whether the decellularized placenta (DP) could serve as natural scaffold material to create a BCP for myocardial repair.
METHODS AND RESULTS
A BCP was created by seeding human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs; 1 × 106/cm2) onto DP. The functional and electrophysiological properties of the BCP were first characterized by in vitro analysis and optical mapping. Next, in vivo therapeutic efficacy of the BCP was evaluated in a rat model of myocardial infarction (MI), created by left descending coronary artery ligation (MI + BCP group), and compared with MI alone (MI group), transplantation of DP (MI + DP group), and hiPSC-CMs (MI + CM group). Cytokine profiling demonstrated that the BCP contained multiple growth and angiogenic factors, including vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor-1, basic fibroblast growth factor, angiogenin, and angiopoietin-2. In vitro optical mapping showed that the BCP exhibited organized mechanical contraction and synchronized electrical propagation. RNA sequencing showed that DP enhanced the maturation of hiPSC-CMs compared with the monolayer of cultured hiPSC-CMs. At 4 weeks follow-up, the BCP significantly improved left ventricular (LV) function, as determined by LV ejection fraction, fractional shortening, + dP/dt, and end-systolic pressure-volume relationship, compared with the MI, MI + DP, and MI + CM groups. Moreover, histological examination revealed that engraftment of the BCP at the infarct zone decreased infarct size and increased cell retention and neovascularization compared with the MI, MI + DP, and MI + CM groups.
CONCLUSIONS
Our results demonstrate that a DP scaffold contains multiple growth and angiogenic factors that enhance the maturation and survival of seeded hiPSC-CMs. Transplantation of a BCP is superior to DP or hiPSC-CMs alone in reducing infarct size and improving cell retention and neovascularization, thus providing a novel therapy for myocardial repair following MI.
Topics: Animals; Cells, Cultured; Disease Models, Animal; Female; Humans; Induced Pluripotent Stem Cells; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Placenta; Pregnancy; Rats; Vascular Endothelial Growth Factor A
PubMed: 33413626
DOI: 10.1186/s13287-020-02066-y -
Cellular and Molecular Life Sciences :... Jan 2020Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal... (Review)
Review
Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinically promising due to their proliferative, migratory, clonogenic and immunomodulatory properties. PMSCs release a plethora of cytokines and chemokines key to angiogenic signaling and facilitate the possibility of delivering PMSC-derived exosomes as a targeted therapy to promote angiogenesis. However, there still remains the challenge of heterogeneity in the isolated populations, questions on the maternal or fetal origin of these cells and the diversity in previously reported isolation and culture conditions. Nonetheless, the growing rate of clinical trials using PMSCs clearly indicates a shift in favor of PMSCs. The overall aim of the review is to highlight the importance of this rather poorly understood cell type and emphasize the need for further investigations into their angiogenic potential as an alternative source for therapeutic angiogenesis.
Topics: Animals; Exosomes; Female; Humans; Mesenchymal Stem Cells; Neovascularization, Physiologic; Placenta; Pregnancy
PubMed: 31468060
DOI: 10.1007/s00018-019-03268-1 -
PloS One 2022Angiogenic growth mediators (AGMs) and oxidative stress (OS) both play essential roles in normal placental vascular development and as such, placental alterations in...
Placental lesions and differential expression of pro-and anti-angiogenic growth mediators and oxidative DNA damage marker in placentae of Ghanaian suboptimal and optimal health status pregnant women who later developed preeclampsia.
BACKGROUND
Angiogenic growth mediators (AGMs) and oxidative stress (OS) both play essential roles in normal placental vascular development and as such, placental alterations in these factors contribute to pre-eclampsia (PE). Suboptimal health status (SHS), an intermediate between health and disease, has been associated with imbalanced AGMs and OS biomarkers. Thus, SHS pregnant women may be at increased risk of developing PE and may present abnormal placental alteration and expression of AGMs and OS compared to optimal health status (OHS) pregnant women. We examined the histopathological morphology, immunohistochemical expression of AGMs antibodies and oxidative DNA damage marker in the placentae of SHS and OHS pregnant women who developed early-onset PE (EO-PE) and late-onset (LO-PE) compared to normotensive pregnancy (NTN-P).
METHODS
This nested case-control study recruited 593 singleton normotensive pregnant women at baseline (10-20 weeks gestation) from the Ghanaian Suboptimal Health Status Cohort Study (GHOACS) undertaken at the Komfo Anokye Teaching Hospital, Ghana. Socio-demographic, clinical and obstetrics data were collected, and a validated SHS questionnaire-25 (SHSQ-25) was used in classifying participants into SHS (n = 297) and OHS (n = 296). Participants were followed until the time of PE diagnosis and delivery (32-42 weeks gestation). Blood samples were collected at the two-time points and were assayed for AGMs; soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PIGF), vascular endothelial growth factor-A (VEGF-A), and soluble endoglin (sEng), and OS biomarkers; 8-hydroxydeoxyguanosine (8-OHdG), 8-epiprostaglandinF2-alpha (8- epi-PGF2α) and total antioxidant capacity (TAC) using ELISA. Placental samples were collected for histopathological and immunohistochemical analysis.
RESULTS
Of the 593 pregnant women, 498 comprising 248 SHS and 250 OHS women returned for delivery and were included in the final analysis. Of the 248 SHS women, 56, 97 and 95 developed EO-PE, LO-PE and NTN-P, respectively, whereas 14, 30 and 206 of the 250 OHS mothers developed EO-PE, LO-PE and NTN-P, respectively. At baseline, SHS_NTN pregnant women had a significant imbalance in AGMs and OS biomarkers compared to OHS_NTN pregnant women (p<0.0001). At the time of PE diagnosis, SHS_NTN-P women who developed EO-PE, LO-PE, and NTN-P had lower serum levels of P1GF, VEGF-A and TAC and correspondingly higher levels of sEng, sFlt-1, 8-epiPGF2α, and 8-OHdG than OHS-NTN-P women who developed EO-PE and LO-PE, NTN-P (p<0.0001). A reduced placental size, increased foetal/placental weight ratio, and a significantly higher proportion of fibrinoid necrosis, infarction, villous fibrin, syncytial knots, calcification, chorangiosis, tunica media/vascular wall hypertrophy and chorioamnionitis was associated with the SHS group who developed PE (EO-PE>LO-PE) more than OHS groups who developed PE (EO-PE>LO-PE) when all were compared to NTN-P (p<0.0001). The intensity of antibody expression of PIGF and VEGF-A were significantly reduced, whereas Flt-1, Eng and 8-OHdG were significantly increased in placentae from SHS-pregnant women who developed EO-PE>LO-PE more than OHS- pregnant women who developed EO-PE>LO-PE when all were compared to NTN-P (p<0.0001).
CONCLUSION
Increased lesions, oxidative DNA damage, and imbalanced expression between pro-and anti-AGMs are associated more with SHS-embodied PE placentae rather than OHS-embodied PE subtypes, thus potentially allowing differential evaluation of PE.
Topics: Antioxidants; Biomarkers; Case-Control Studies; Cohort Studies; Endoglin; Female; Fetal Weight; Ghana; Health Status; Humans; Oxidative Stress; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnant Women; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1
PubMed: 35312727
DOI: 10.1371/journal.pone.0265717 -
Romanian Journal of Morphology and... 2023The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown.
BACKGROUND
The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown.
AIM
We present this original paper where we analyzed 60 parturients, at term, 30 without associated infection (C-) and 30 with associated infection (C+), present at birth.
METHODS
We analyzed the blood count and placental microscopic structure through classical and immunohistochemical staining and observed the placental areas affected by the presence of SARS-CoV-2.
RESULTS
SARS-CoV-2 infection was accompanied by a decrease in the number of lymphocytes, the number of platelets and the presence of placental structural changes, identifying extensive areas of amyloid deposits, placental infarcts, vascular thrombosis, syncytial knots, with a decrease in placental vascular density and the presence of infection in the cells located at decidual level, at syncytiotrophoblast level and at the level of the cells of the chorionic plate, still without overcoming this barrier and without causing any fetal infection in the analyzed cases.
CONCLUSIONS
This study shows that the invasion of SARS-CoV-2 in the placenta can produce significant structural changes, with a decrease in placental vascular density that can have significant implications on proper fetal perfusion. Also, the presence of immunoreactivity at the level of decidua, the placental villi, as well as the chorionic plate proves that the virus can overcome the maternal-fetal barrier. However, in the analyzed cases there were no fetal infections at birth, which may show that local placental factors can be a protective filter for the fetus.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Placenta; SARS-CoV-2; COVID-19; Immune System; Placenta Diseases
PubMed: 38184836
DOI: 10.47162/RJME.64.4.12 -
Diagnostics (Basel, Switzerland) Sep 2022Adverse perinatal outcomes, such as increased risks of pre-eclampsia, miscarriage, premature birth, and stillbirth have been reported in SARS-CoV-2 infection. For a...
Adverse perinatal outcomes, such as increased risks of pre-eclampsia, miscarriage, premature birth, and stillbirth have been reported in SARS-CoV-2 infection. For a better understanding of COVID-19 complications in pregnancy, histopathological changes in the placenta, which is the interface between mother and foetus, could be the place to look at. The aim of this study was to determine placental histopathological changes and their role in preterm birth in pregnant women with SARS-CoV-2 infection. We performed a prospective, observational study in a COVID-only hospital, which included 39 pregnant women with SARS-CoV-2 infection and preterm birth compared with a control group of 39 women COVID-19 negative with preterm birth and a placental pathology exam available. The microscopic examination of all placentas revealed placental infarction (64.1% vs. 30.8%), decidual arteriopathy (66.7% vs. 23.1%), intervillous thrombi (53.8% vs. 38.5%), perivillous fibrin deposits (59% vs. 46.2%), inflammatory infiltrate (69.2% vs. 46.2%), chorangiosis (17.9% vs. 10.3%), and accelerated maturation of the villi (23.1% vs. 28.2%).
PubMed: 36292012
DOI: 10.3390/diagnostics12102323 -
Placenta Jul 2016Stillbirth, preeclampsia, and gestational hypertension (PE/GH) have similar clinical risk factors and redundant placental pathology. We aim to discern if stillbirth with...
INTRODUCTION
Stillbirth, preeclampsia, and gestational hypertension (PE/GH) have similar clinical risk factors and redundant placental pathology. We aim to discern if stillbirth with PE/GH has a particular phenotype by comparing stillbirths with and without PE/GH.
METHODS
Secondary analysis of the Stillbirth Collaborative Research Network, a population-based cohort study of all stillbirths and a sample of live births from 2006 to 2008 in five catchment areas. We compared placental pathology between stillbirths and with and without PE/GH, stratified by term or preterm. We also compared placental pathology between stillbirths and live births with PE/GH.
RESULTS
79/518 stillbirths and 140/1200 live births had PE/GH. Amongst preterm stillbirths, there was higher feto-placental ratio in PE/GH pregnancies (OR 1.24 [1.11, 1.37] per unit increase), and there were more parenchymal infarctions (OR 5.77 [3.18, 10.47]). Among PE/GH pregnancies, stillbirths had increased maternal and fetal vascular lesions, including retroplacental hematoma, parenchymal infarction, fibrin deposition, fetal vascular thrombi, and avascular villi.
DISCUSSION
Stillbirth pregnancies are overwhelmingly associated with placental lesions. Parenchymal infarctions are more common in PE/GH preterm stillbirths, but there is significant overlap in lesions found in stillbirths and PE/GH.
Topics: Adolescent; Age Factors; Cohort Studies; Female; Fetal Death; Gestational Age; Humans; Hypertension, Pregnancy-Induced; Placenta; Pregnancy; Pregnancy Complications; Stillbirth; Young Adult
PubMed: 27324101
DOI: 10.1016/j.placenta.2016.04.020