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Frontiers in Immunology 2019Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide, affecting 2-8% of all pregnancies. Studies suggest a link between... (Review)
Review
Preeclampsia is one of the leading causes of maternal and neonatal mortality and morbidity worldwide, affecting 2-8% of all pregnancies. Studies suggest a link between complement activation and preeclampsia. The complement system plays an essential role in the innate immunity, leading to opsonization, inflammation, and elimination of potential pathogens. The complement system also provides a link between innate and adaptive immunity and clearance of immune complexes and apoptotic cells. During pregnancy there is increased activity of the complement system systemically. However, locally at the placenta, complement inhibition is crucial for the maintenance of a normal pregnancy. Inappropriate or excessive activation of the complement system at the placenta is likely involved in placental dysfunction, and is in turn associated with pregnancy complications like preeclampsia. Therefore, modulation of the complement system could be a potential therapeutic target to prevent pregnancy complications such as preeclampsia. This review, based on a systematic literature search, gives an overview of the complement system and its activation locally in the placenta and systemically during healthy pregnancies and during complicated pregnancies, with a focus on preeclampsia. Furthermore, this review describes results of animal and human studies with a focus on the complement system in pregnancy, and the role of the complement system in placental dysfunction. Various clinical and animal studies provide evidence that dysregulation of the complement system is associated with placental dysfunction and therefore with preeclampsia. Several drugs are used for prevention and treatment of preeclampsia in humans and animal models, and some of these drugs work through complement modulation. Therefore, this review further discusses these studies examining pharmaceutical interventions as treatment for preeclampsia. These observations will help direct research to generate new target options for prevention and treatment of preeclampsia, which include direct and indirect modulation of the complement system.
Topics: Complement Activation; Complement System Proteins; Female; Humans; Placenta; Placenta Diseases; Pre-Eclampsia; Pregnancy
PubMed: 32010144
DOI: 10.3389/fimmu.2019.03098 -
Seminars in Ultrasound, CT, and MR Feb 1996The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Included in its many functions are fetal oxygenation and nutrition as well as... (Review)
Review
The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Included in its many functions are fetal oxygenation and nutrition as well as a myriad of endocrinological contributions and protein synthesis. The sonologist is strongly encouraged to study this amazing structure with ultrasound because significant pathology afflicts the placenta, often before affecting the fetus. Placental abnormalities, therefore, can be an "early warning system" for fetal problems. Recognition of clinically important lesions (abruption, accreta) as well as important anatomical variants (intervillous thrombosis, septal cyst) is crucial for the physician who performs and interprets prenatal ultrasound. This article discusses the common abnormalities of the placenta and highlights some correlative pathological processes, which will serve to enhance the reader's understanding of sonographic findings. A practical approach is presented with respect to assessment of the hypoechoic lesion, placental infarction, thick placenta, placenta previa, abruption, placenta accreta, and placental tumors.
Topics: Female; Hemangioma; Humans; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Neoplastic; Trophoblastic Neoplasms; Ultrasonography, Prenatal; Uterine Neoplasms
PubMed: 8845194
DOI: 10.1016/s0887-2171(96)90045-1 -
Placenta Dec 2017Bidirectional transplacental exchange characterizes human pregnancy. Cells exchanged between mother and fetus can durably persist as microchimerism and may have both... (Review)
Review
Bidirectional transplacental exchange characterizes human pregnancy. Cells exchanged between mother and fetus can durably persist as microchimerism and may have both short- and long-term consequences for the recipient. The amount, type, and persistence of microchimerism are influenced by obstetric characteristics, pregnancy complications, exposures to infection, and other factors. A reproductive-aged woman enters pregnancy harboring previously acquired microchimeric "grafts," which may influence her preconception health and her subsequent pregnancy outcomes. Many questions remain to be answered about microchimerism with broad-ranging implications. This review will summarize key aspects of this field of research and propose important questions to be addressed moving forward.
Topics: Chimerism; Female; Fetus; Humans; Malaria; Maternal-Fetal Exchange; Placenta Diseases; Pregnancy
PubMed: 28911790
DOI: 10.1016/j.placenta.2017.08.071 -
Acta Obstetricia Et Gynecologica... Aug 2020Low-lying placentas, placenta previa and abnormally invasive placentas are the most frequently occurring placental abnormalities in location and anatomy. These...
Low-lying placentas, placenta previa and abnormally invasive placentas are the most frequently occurring placental abnormalities in location and anatomy. These conditions can have serious consequences for mother and fetus mainly due to excessive blood loss before, during or after delivery. The incidence of such abnormalities is increasing, but treatment options and preventive strategies are limited. Therefore, it is crucial to understand the etiology of placental abnormalities in location and anatomy. Placental formation already starts at implantation and therefore disorders during implantation may cause these abnormalities. Understanding of the normal placental structure and development is essential to comprehend the etiology of placental abnormalities in location and anatomy, to diagnose the affected women and to guide future research for treatment and preventive strategies. We reviewed the literature on the structure and development of the normal placenta and the placental development resulting in low-lying placentas, placenta previa and abnormally invasive placentas.
Topics: Adult; Female; Humans; Placenta Diseases; Pregnancy
PubMed: 32108320
DOI: 10.1111/aogs.13834 -
The Journal of Physiology Jul 2009
Topics: Female; Fetal Growth Retardation; Humans; Maternal-Fetal Exchange; Placenta; Placenta Diseases; Pregnancy
PubMed: 19505982
DOI: 10.1113/jphysiol.2009.175968 -
Journal of Perinatal Medicine Jun 2022To determine whether placental vascular pathology and impaired placental exchange due to maturational defects are involved in the etiology of spontaneous preterm labor... (Observational Study)
Observational Study
OBJECTIVES
To determine whether placental vascular pathology and impaired placental exchange due to maturational defects are involved in the etiology of spontaneous preterm labor and delivery in cases without histologic acute chorioamnionitis.
METHODS
This was a retrospective, observational study. Cases included pregnancies that resulted in spontaneous preterm labor and delivery (<37 weeks), whereas uncomplicated pregnancies that delivered fetuses at term (≥37-42 weeks of gestation) were selected as controls. Placental histological diagnoses were classified into three groups: lesions of maternal vascular malperfusion, lesions of fetal vascular malperfusion, and placental microvasculopathy, and the frequency of each type of lesion in cases and controls was compared. Moreover, we specifically searched for villous maturational abnormalities in cases and controls. Doppler velocimetry of the umbilical and uterine arteries were performed in a subset of patients.
RESULTS
There were 184 cases and 2471 controls, of which 95 and 1178 had Doppler studies, respectively. The frequency of lesions of maternal vascular malperfusion was greater in the placentas of patients with preterm labor than in the control group [14.1% (26/184) vs. 8.8% (217/2471) (p=0.023)]. Disorders of villous maturation were more frequent in the group with preterm labor than in the control group: 41.1% (39/95) [delayed villous maturation in 31.6% (30/95) vs. 2.5% (13/519) in controls and accelerated villous maturation in 9.5% (9/95) vs. none in controls].
CONCLUSIONS
Maturational defects of placental villi were associated with approximately 41% of cases of unexplained spontaneous preterm labor and delivery without acute inflammatory lesions of the placenta and with delivery of appropriate-for-gestational-age fetuses.
Topics: Chorioamnionitis; Female; Gestational Age; Humans; Infant, Newborn; Obstetric Labor, Premature; Placenta; Placenta Diseases; Pregnancy
PubMed: 35246973
DOI: 10.1515/jpm-2021-0681 -
Journal of Cellular and Molecular... Mar 2020Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for...
OBJECTIVES
Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for clinical diagnosis and treatment.
MATERIALS AND METHODS
Blood and placental samples were collected from included patients. The distribution and expression of CXCL12, CXCR4 and CXCR7 proteins in the paraffin of placental tissue in the included cases were analysed, and we analyse the downstream pathways or key proteins involved in cell invasion.
RESULTS
Firstly, our results determined that CXCL12 and CXCR4/CXCR7 were increased in extravillous trophoblastic cell (CXCL12: P < .001; CXCR4: P < .001; CXCR7: P < .001), and the expression levels were closely related to the invasion depth of trophoblastic cells. Secondly, CXCL12 has the potential to become a biochemical indicator of PAS since the high expression of placental trophoblast CXCL12 may be an important source of blood CXCL12. Using lentivirus-mediated RNA interference and overexpression assay, it was found that both chemokine CXCL12 and receptor CXCR4/CXCR7 are associated with regulation of trophoblast cell proliferation, migration and invasion. Further results proved that through the activating the phosphorylation and increasing the expression of MLC and AKT proteins in the Rho/rock, PI3K/AKT signalling pathway, CXCL12, CXCR4 and CXCR7 could up-regulate the expression of RhoA, Rac1 and Cdc42 proteins to promote the migration and invasion of extravillous trophoblastic cell and ultimately formate the placenta accrete compare to the normal placenta.
CONCLUSIONS
Our research proved that trophoblasts may contribute to a PAS-associated increase in CXCL12 levels in maternal blood. CXCL12 is not only associated with biological roles of PAS, but may also be potential for prediction of PAS.
Topics: Adult; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemokine CXCL12; Female; Gene Expression Regulation; Humans; Phosphorylation; Placenta Accreta; Placenta Diseases; Pregnancy; Receptors, CXCR; Receptors, CXCR4; Trophoblasts
PubMed: 31991051
DOI: 10.1111/jcmm.14990 -
Ultrasound in Obstetrics & Gynecology :... May 2019To evaluate the transgenerational transmission of small-for-gestational age (SGA).
OBJECTIVE
To evaluate the transgenerational transmission of small-for-gestational age (SGA).
METHODS
This was a cohort study of a random sample of 2043 offspring delivered between 1975 and 1993 at Hospital Sant Joan de Déu in Barcelona. Exclusion criteria were multiple pregnancy, aneuploidy or genetic syndrome, major birth defects, severe mental disease and macrosomia. Eligible individuals were contacted and those with at least one offspring were included in the study. Participants were classified according to the presence of SGA (defined as birth weight < 10 percentile) at birth. Multiple regression analysis was used to determine the presence of SGA or placenta-mediated disease (defined as the presence of SGA, pre-eclampsia, gestational hypertension and/or placental abruption) in the following generation.
RESULTS
Of 623 individuals who agreed to participate, 152 (72 born SGA and 80 born appropriate-for-gestational age (AGA)) were reported to have at least one child. Descendants of SGA individuals presented with a lower birth-weight percentile (median, 26 (interquartile range (IQR), 7-52) vs 43 (IQR, 19-75); P < 0.001) and a higher prevalence of SGA (40.3% vs 16.3%; P = 0.001) and placenta-mediated disease (43.1% vs 17.5%; P = 0.001) than did the offspring of AGA individuals. After adjustment for confounding variables, parental SGA background was associated with an almost three-fold increased risk of subsequent SGA or any placenta-mediated disease in the following generation. This association was stronger in SGA mothers than in SGA fathers.
CONCLUSIONS
Our data provide evidence suggesting a transgenerational transmission of SGA, highlighting the importance of public health strategies for preventing intrauterine growth impairment. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Cohort Studies; Female; Genetic Predisposition to Disease; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Male; Placenta Diseases; Pregnancy; Prevalence; Regression Analysis; Spain; Young Adult
PubMed: 30207012
DOI: 10.1002/uog.20119 -
American Journal of Obstetrics and... Oct 2015MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through... (Review)
Review
MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade, a flurry of studies has shed light on placental miRNAs but has also raised many questions regarding the scope of their biologic action. Moreover, the recognition that miRNAs of placental origin are released continually in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. Although this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology.
Topics: Biomarkers; Extracellular Space; Female; Humans; MicroRNAs; Placenta Diseases; Pregnancy
PubMed: 26428496
DOI: 10.1016/j.ajog.2015.05.057 -
Ultrasound in Obstetrics & Gynecology :... Apr 2020To evaluate the diagnostic accuracy of a new ultrasound sign, intracervical lakes (ICL), in predicting the presence of placenta accreta spectrum (PAS) disorder and...
OBJECTIVE
To evaluate the diagnostic accuracy of a new ultrasound sign, intracervical lakes (ICL), in predicting the presence of placenta accreta spectrum (PAS) disorder and delivery outcome in patients with placenta previa or low-lying placenta.
METHODS
This was a retrospective multicenter study of women with placenta previa or low-lying placenta at ≥ 26 weeks' gestation, who were referred to three Italian tertiary units from January 2015 to September 2018. The presence of ICL, defined as tortuous anechoic spaces within the cervix which appeared to be hypervascular on color Doppler, was evaluated on ultrasound images obtained at the time of referral. The primary aim was to explore the diagnostic accuracy of ICL in detecting the presence and depth of PAS disorder. The secondary aim was to explore the accuracy of this sign in predicting total estimated blood loss, antepartum bleeding, major postpartum hemorrhage at the time of Cesarean section and need for Cesarean hysterectomy. The diagnostic accuracy of ICL in combination with typical sonographic signs of PAS disorder, was assessed by computing summary estimates of sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and diagnostic odds ratios (DOR).
RESULTS
A total of 332 women with placenta previa or low-lying placenta were included in the analysis, with a median maternal age of 33.0 (interquartile range, 29.0-37.0) years. ICL were noted in 15.1% of patients. On logistic regression analysis, the presence of ICL was associated independently with major postpartum hemorrhage (odds ratio (OR), 3.3 (95% CI, 1.6-6.5); P < 0.001), Cesarean hysterectomy (OR, 7.0 (95% CI, 2.1-23.9); P < 0.001) and placenta percreta (OR, 2.8 (95% CI, 1.3-5.8); P ≤ 0.01), but not with the presence of any PAS disorder (OR, 1.6 (95% CI, 0.7-3.5); P = 0.2). Compared with the group of patients without ultrasound signs of PAS disorder, the presence of at least one typical sonographic sign of PAS disorder in combination with ICL had a DOR of 217.2 (95% CI, 27.7-1703.4; P < 0.001) for placenta percreta and of 687.4 (95% CI, 121.4-3893.0; P < 0.001) for Cesarean hysterectomy.
CONCLUSION
ICL may represent a marker of deep villus invasion in women with suspected PAS disorder on antenatal sonography and anticipate the occurrence of severe maternal morbidity. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Biomarkers; Cervix Uteri; Cesarean Section; Female; Humans; Hysterectomy; Placenta Accreta; Placenta Diseases; Placenta Previa; Predictive Value of Tests; Pregnancy; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 31503353
DOI: 10.1002/uog.21866