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Frontiers in Endocrinology 2022The placenta plays a fundamental role during pregnancy for fetal growth and development. A suboptimal placental function may result in severe consequences during the... (Review)
Review
The placenta plays a fundamental role during pregnancy for fetal growth and development. A suboptimal placental function may result in severe consequences during the infant's first years of life. In recent years, a new field known as neuroplacentology has emerged and it focuses on the role of the placenta in fetal and neonatal brain development. Because of the limited data, our aim was to provide a narrative review of the most recent knowledge about the relation between placental lesions and fetal and newborn neurological development. Papers published online from 2000 until February 2022 were taken into consideration and particular attention was given to articles in which placental lesions were related to neonatal morbidity and short-term and long-term neurological outcome. Most research regarding the role of placental lesions in neurodevelopment has been conducted on fetal growth restriction and preterm infants. Principal neurological outcomes investigated were periventricular leukomalacia, intraventricular hemorrhages, neonatal encephalopathy and autism spectrum disorder. No consequences in motor development were found. All the considered studies agree about the crucial role played by placenta in fetal and neonatal neurological development and outcome. However, the causal mechanisms remain largely unknown. Knowledge on the pathophysiological mechanisms and on placenta-related risks for neurological problems may provide clues for early interventions aiming to improve neurological outcomes, especially among pediatricians and child psychiatrists.
Topics: Autism Spectrum Disorder; Female; Fetal Growth Retardation; Humans; Infant; Infant, Newborn; Infant, Premature; Placenta; Placenta Diseases; Pregnancy
PubMed: 36060976
DOI: 10.3389/fendo.2022.936171 -
Frontiers in Endocrinology 2023Placenta accreta spectrum disorder (PAS) is a kind of disease of placentation defined as abnormal trophoblast invasion of part or all of the placenta into the... (Review)
Review
Placenta accreta spectrum disorder (PAS) is a kind of disease of placentation defined as abnormal trophoblast invasion of part or all of the placenta into the myometrium, even penetrating the uterus. Decidual deficiency, abnormal vascular remodeling in the maternal-fetal interface, and excessive invasion by extravillous trophoblast (EVT) cells contribute to its onset. However, the mechanisms and signaling pathways underlying such phenotypes are not fully understood, partly due to the lack of suitable experimental animal models. Appropriate animal models will facilitate the comprehensive and systematic elucidation of the pathogenesis of PAS. Due to the remarkably similar functional placental villous units and hemochorial placentation to humans, the current animal models of PAS are based on mice. There are various mouse models induced by uterine surgery to simulate different phenotypes of PAS, such as excessive invasion of EVT or immune disturbance at the maternal-fetal interface, which could define the pathological mechanism of PAS from the perspective of the "soil." Additionally, genetically modified mouse models could be used to study PAS, which is helpful to exploring the pathogenesis of PAS from the perspectives of both "soil" and "seed," respectively. This review details early placental development in mice, with a focus on the approaches of PAS modeling. Additionally, the strengths, limitations and the applicability of each strategy and further perspectives are summarized to provide the theoretical foundation for researchers to select appropriate animal models for various research purposes. This will help better determine the pathogenesis of PAS and even promote possible therapy.
Topics: Pregnancy; Humans; Female; Animals; Mice; Placenta Accreta; Placenta; Disease Models, Animal; Myometrium; Epithelial Cells
PubMed: 37223034
DOI: 10.3389/fendo.2023.1118168 -
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 -
Frontiers in Endocrinology 2022Emerging evidence has shown that fertilization (IVF) is associated with higher risks of certain placental abnormalities or complications, such as placental abruption,...
INTRODUCTION
Emerging evidence has shown that fertilization (IVF) is associated with higher risks of certain placental abnormalities or complications, such as placental abruption, preeclampsia, and preterm birth. However, there is a lack of large population-based analysis focusing on placental abnormalities or complications following IVF treatment. This study aimed to estimate the absolute risk of placental abnormalities or complications during IVF-conceived pregnancy.
METHODS
We conducted a retrospective cohort study of 16 535 852 singleton pregnancies with delivery outcomes in China between 2013 and 2018, based on the Hospital Quality Monitoring System databases. Main outcomes included placental abnormalities (placenta previa, placental abruption, placenta accrete, and abnormal morphology of placenta) and placenta-related complications (gestational hypertension, preeclampsia, eclampsia, preterm birth, fetal distress, and fetal growth restriction (FGR)). Poisson regression modeling with restricted cubic splines of exact maternal age was used to estimate the absolute risk in both the IVF and non-IVF groups.
RESULTS
The IVF group (n = 183 059) was more likely than the non-IVF group (n = 16 352 793) to present placenta previa (aRR: 1.87 [1.83-1.91]), placental abruption (aRR: 1.16 [1.11-1.21]), placenta accrete (aRR: 2.00 [1.96-2.04]), abnormal morphology of placenta (aRR: 2.12 [2.07 to 2.16]), gestational hypertension (aRR: 1.55 [1.51-1.59]), preeclampsia (aRR: 1.54 [1.51-1.57]), preterm birth (aRR: 1.48 [1.46-1.51]), fetal distress (aRR: 1.39 [1.37-1.42]), and FGR (aRR: 1.36 [1.30-1.42]), but no significant difference in eclampsia (aRR: 0.91 [0.80-1.04]) was found. The absolute risk of each outcome with increasing maternal age in both the IVF and non-IVF group presented two patterns: an upward curve showing in placenta previa, placenta accreta, abnormal morphology of placenta, and gestational hypertension; and a J-shape curve showing in placental abruption, preeclampsia, eclampsia, preterm birth, fetal distress, and FGR.
CONCLUSION
IVF is an independent risk factor for placental abnormalities and placental-related complications, and the risk is associated with maternal age. Further research is needed to evaluate the long-term placenta-related chronic diseases of IVF patients and their offspring.
Topics: Abruptio Placentae; Eclampsia; Female; Fertilization; Fetal Distress; Fetal Growth Retardation; Humans; Hypertension, Pregnancy-Induced; Infant, Newborn; Placenta; Placenta Previa; Pre-Eclampsia; Pregnancy; Premature Birth; Retrospective Studies
PubMed: 35846290
DOI: 10.3389/fendo.2022.924070 -
International Journal of Molecular... Sep 2023Global health efforts have increased against infectious diseases, but issues persist with pathogens like Group B Streptococcus (GBS). Preclinical studies have elaborated... (Review)
Review
Global health efforts have increased against infectious diseases, but issues persist with pathogens like Group B Streptococcus (GBS). Preclinical studies have elaborated on the mechanistic process of GBS-induced chorioamnionitis and its impact on the fetal programming of chronic neuropsychiatric diseases. GBS inoculation in rodents demonstrated the following: (i) silent and self-limited placental infection, similar to human chorioamnionitis; (ii) placental expression of chemokines attracting polymorphonuclear (PMN) cells; (iii) in vitro cytokine production; (iv) PMN infiltration in the placenta (histologic hallmark of human chorioamnionitis), linked to neurobehavioral impairments like cerebral palsy and autism spectrum disorders (ASD); (v) upregulation of interleukin-1β (IL-1β) in the placenta and fetal blood, associated with higher ASD risk in humans; (vi) sex-specific effects, with higher IL-1β release and PMN recruitment in male placenta; (vii) male offspring exhibiting ASD-like traits, while female offspring displayed attention deficit and hyperactivity disorder (ADHD)-like traits; (viii) IL-1 and/or NF-kB blockade alleviate placental and fetal inflammation, as well as subsequent neurobehavioral impairments. These findings offer potential therapeutic avenues, including sex-adapted anti-inflammatory treatment (e.g., blocking IL-1; repurposing of FDA-approved IL-1 receptor antagonist (IL-1Ra) treatment). Blocking the IL-1 pathway offers therapeutic potential to alleviate chorioamnionitis-related disabilities, presenting an opportunity for a human phase II RCT that uses IL-1 blockade added to the classic antibiotic treatment of chorioamnionitis.
Topics: Pregnancy; Humans; Female; Male; Chorioamnionitis; Placenta; Autism Spectrum Disorder; Brain Injuries; Streptococcus; Interleukin-1
PubMed: 37762401
DOI: 10.3390/ijms241814090 -
Ultrasound in Obstetrics & Gynecology :... May 2017
Review
Topics: Cesarean Section; Female; Humans; Hysterectomy; Magnetic Resonance Imaging; Placenta Accreta; Placenta, Retained; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Terminology as Topic
PubMed: 28120421
DOI: 10.1002/uog.17417 -
Placenta Aug 2023Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68 cells in the intervillous space. CHI...
INTRODUCTION
Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68 cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance. The pathophysiologic mechanism of CHI is unclear, but it appears to be immunologically driven. The aim of this study was to obtain a better understanding of the phenotype of the cellular infiltrate in CHI.
METHOD
We used imaging mass cytometry to achieve in-depth visualization of the intervillous maternal immune cells and investigated their spatial orientation in situ in relation to the fetal syncytiotrophoblast.
RESULTS
We found three phenotypically distinct CD68HLA-DRCD38 cell clusters that were unique for CHI. Additionally, syncytiotrophoblast cells in the vicinity of these CD68HLA-DRCD38 cells showed decreased expression of the immunosuppressive enzyme CD39.
DISCUSSION
The current results provide novel insight into the phenotype of CD68 cells in CHI. The identification of unique CD68 cell clusters will allow more detailed analysis of their function and could result in novel therapeutic targets for CHI.
Topics: Pregnancy; Humans; Female; Placenta Diseases; Placenta; Pregnancy Outcome; Histiocytes; Abortion, Spontaneous; Chorionic Villi
PubMed: 37300938
DOI: 10.1016/j.placenta.2023.05.007 -
The Journal of Maternal-fetal &... Dec 2023To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect...
OBJECTIVE
To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect to maternal age at first cesarean delivery.
METHODS
This retrospective study included clinical data from 9981 singleton pregnant women with a history of cesarean delivery at 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. The study population was divided into four groups (<2, 2-5, 5-10, ≥10 years of the interval) according to the inter-pregnancy interval. The rate of placenta previa and placenta accreta spectrum among the four groups was compared, and multivariate logistic regression was used to analyze the relationship between inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery.
RESULTS
Compared to women aged 30-34 years old at first cesarean delivery, the risk of placenta previa (aRR, 1.48; 95% CI, 1.16-1.88) and placenta accreta spectrum (aRR, 1.74; 95% CI, 1.28-2.35) were higher among women aged 18-24. Multivariate regression results showed that women at 18-24 with <2 years intervals exhibited a 5.05-fold increased risk for placenta previa compared with those with 2-5-year intervals (aRR, 5.05; 95% CI, 1.13-22.51). In addition, women aged 18-24 with less than 2 years intervals had an 8.44 times greater risk of developing PAS than women aged 30-34 with 2 to 5 years intervals (aRR, 8.44; 95% CI, 1.82-39.26).
CONCLUSIONS
The findings of this study suggested that short inter-pregnancy intervals were associated with increased risks for placenta previa, and placenta accreta spectrum for women under 25 years at first cesarean delivery, which may be partly attributed to obstetrical outcomes.
Topics: Pregnancy; Female; Humans; Adult; Maternal Age; Placenta Previa; Retrospective Studies; Placenta Accreta; Birth Intervals; Risk Factors
PubMed: 36966813
DOI: 10.1080/14767058.2023.2192853 -
Biochimica Et Biophysica Acta.... Dec 2020Gestational diabetes mellitus (GDM) is a disease of pregnancy that is associated with d-glucose intolerance and foeto-placental vascular dysfunction. GMD causes... (Review)
Review
Gestational diabetes mellitus (GDM) is a disease of pregnancy that is associated with d-glucose intolerance and foeto-placental vascular dysfunction. GMD causes mitochondrial dysfunction in the placental endothelium and trophoblast. Additionally, GDM is associated with reduced placental oxidative phosphorylation due to diminished activity of the mitochondrial FF-ATP synthase (complex V). This phenomenon may result from a higher generation of reactive superoxide anion and nitric oxide. Placental mitochondrial biogenesis and mitophagy work in concert to maintain cell homeostasis and are vital mechanisms securing the efficient generation of ATP, whose demand is higher in pregnancy, ensuring foetal growth and development. Additional factors disturbing placental ATP synthase activity in GDM include pre-gestational maternal obesity or overweight, intracellular pH, miRNAs, fatty acid oxidation, and foetal (and 'placental') sex. GDM is also associated with maternal and foetal hyperinsulinaemia, altered circulating levels of adiponectin and leptin, and the accumulation of extracellular adenosine. Here, we reviewed the potential interplay between these molecules or metabolic conditions on the mechanisms of mitochondrial dysfunction in the foeto-placental unit in GDM pregnancies.
Topics: Animals; Diabetes, Gestational; Female; Humans; Mitochondria; Placenta Diseases; Pregnancy
PubMed: 32866635
DOI: 10.1016/j.bbadis.2020.165948 -
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