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International Journal of Molecular... Feb 2021Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of... (Review)
Review
Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of multiple diseases, including neurodegenerative diseases, cardiac failure, and renal failure. Aggregates could pose a hazard for cell survival. Cells exhibit three main mechanisms against the accumulation of aggregates: protein refolding by upregulation of chaperones, reduction of protein overload by translational inhibition, and protein degradation by the ubiquitin-proteasome and autophagy-lysosome systems. Deletion of autophagy-related genes reportedly contributes to intracellular protein aggregation in vivo. Some proteins recognized in aggregates in preeclamptic placentas include those involved in neurodegenerative diseases. As aggregates are derived both intracellularly and extracellularly, special endocytosis for extracellular aggregates also employs the autophagy machinery. In this review, we discuss how the deficiency of aggrephagy and/or macroautophagy leads to poor placentation, resulting in preeclampsia or fetal growth restriction.
Topics: Animals; Female; Humans; Lysosomes; Macroautophagy; Placenta; Pre-Eclampsia; Pregnancy; Protein Aggregation, Pathological
PubMed: 33670947
DOI: 10.3390/ijms22052432 -
Biology of Sex Differences Dec 2022Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can...
BACKGROUND
Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can have lifelong health outcomes. Yet, sex differences in gene expression within the placenta at different timepoints throughout pregnancy and comparisons to adult tissues remains poorly characterized.
METHODS
Here, we collect and characterize sex differences in gene expression in term placentas (≥ 36.6 weeks; 23 male XY and 27 female XX). These are compared with sex differences in previously collected first trimester placenta samples and 42 non-reproductive adult tissues from GTEx.
RESULTS
We identify 268 and 53 sex-differentially expressed genes in the uncomplicated late first trimester and term placentas, respectively. Of the 53 sex-differentially expressed genes observed in the term placentas, 31 are also sex-differentially expressed genes in the late first trimester placentas. Furthermore, sex differences in gene expression in term placentas are highly correlated with sex differences in the late first trimester placentas. We found that sex-differential gene expression in the term placenta is significantly correlated with sex differences in gene expression in 42 non-reproductive adult tissues (correlation coefficient ranged from 0.892 to 0.957), with the highest correlation in brain tissues. Sex differences in gene expression were largely driven by gene expression on the sex chromosomes. We further show that some gametologous genes (genes with functional copies on X and Y) will have different inferred sex differences if the X-linked gene expression in females is compared to the sum of the X-linked and Y-linked gene expression in males.
CONCLUSIONS
We find that sex differences in gene expression are conserved in late first trimester and term placentas and that these sex differences are conserved in adult tissues. We demonstrate that there are sex differences associated with innate immune response in late first trimester placentas but there is no significant difference in gene expression of innate immune genes between sexes in healthy full-term placentas. Finally, sex differences are predominantly driven by expression from sex-linked genes.
Topics: Pregnancy; Female; Male; Adult; Humans; Sex Characteristics; Placenta; Pregnancy Trimester, First
PubMed: 36550527
DOI: 10.1186/s13293-022-00470-y -
Reproductive Sciences (Thousand Oaks,... Jun 2022Fetal sex affects the risk of pregnancy complications and the long-term effects of prenatal environment on health. Some have hypothesized that growth strategies differ... (Review)
Review
Fetal sex affects the risk of pregnancy complications and the long-term effects of prenatal environment on health. Some have hypothesized that growth strategies differ between the sexes, whereby males prioritize growth whereas females are more responsive to their environment. This review evaluates the role of the placenta in such strategies, focusing on (1) mechanisms underlying sexual dimorphism in gene expression, (2) the nature and extent of sexual dimorphism in placental gene expression, (3) sexually dimorphic responses to nutrient supply, and (4) sexual dimorphism in morphology and histopathology. The sex chromosomes contribute to sex differences in placental gene expression, and fetal hormones may play a role later in development. Sexually dimorphic placental gene expression may contribute to differences in the prevalence of complications such as preeclampsia, although this link is not clear. Placental responses to nutrient supply frequently show sexual dimorphism, but there is no consistent pattern where one sex is more responsive. There are sex differences in the prevalence of placental histopathologies, and placental changes in pregnancy complications, but also many similarities. Overall, no clear patterns support the hypothesis that females are more responsive to the maternal environment, or that males prioritize growth. While male fetuses are at greater risk of a variety of complications, total prenatal mortality is higher in females, such that males exposed to early insults may be more likely to survive and be observed in studies of adverse outcomes. Going forward, robust statistical approaches to test for sex-dependent effects must be more widely adopted to reduce the incidence of spurious results.
Topics: Female; Fetal Development; Humans; Male; Placenta; Pre-Eclampsia; Pregnancy; Sex Characteristics
PubMed: 34699045
DOI: 10.1007/s43032-021-00780-3 -
Reproductive Sciences (Thousand Oaks,... Nov 2017Almost every part of our body has a coevolved microbial community. The expressed microbial genes comprise the various microbiomes that play important roles in normal... (Review)
Review
Almost every part of our body has a coevolved microbial community. The expressed microbial genes comprise the various microbiomes that play important roles in normal physiology and development. The various microbiomes are separate, yet often connected, with the species composition of one affecting others. The female reproductive system microbiomes (eg, vaginal, placental, and mammary/milk) remain less well explored than the gut microbiome although they comprise a large proportion of the female microbial network. This review examines the evidence for interconnectivity between the female reproductive microbiomes, other maternal microbiomes, and developing infant microbiomes and the potential roles of each in health and disease. Disruptions in maternal microbiomes may be linked to pregnancy complications and maternal, fetal, and neonatal health. The diversity of the vaginal microbiome's makeup, which appears to vary across ethnicity, has led researchers to reconsider the idea of a "healthy" or "normal" vaginal microbial community. Less is known about the possible placental microbiome, although an association between the placenta's bacterial makeup and preterm labor and other pregnancy complications is being investigated. The mammary/milk microbiome appears to be influenced by maternal characteristics and may play a role in inoculating the infant but may also be affected by the infant's oral microbiome. Probiotic therapies such as "vaginal seeding" offer potential health benefits but require more rigorous testing. Exploring the reproductive microbiomes in detail and pairing this information with an individual's detailed medical history will provide a more complete picture of the status and importance of the microbial network to health.
Topics: Animals; Female; Humans; Infant, Newborn; Male; Microbiota; Milk, Human; Placenta; Pregnancy; Reproduction; Vagina
PubMed: 28322134
DOI: 10.1177/1933719117698577 -
Medical Image Analysis Jan 2023Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US...
Automatic segmentation of the placenta in fetal ultrasound (US) is challenging due to the (i) high diversity of placenta appearance, (ii) the restricted quality in US resulting in highly variable reference annotations, and (iii) the limited field-of-view of US prohibiting whole placenta assessment at late gestation. In this work, we address these three challenges with a multi-task learning approach that combines the classification of placental location (e.g., anterior, posterior) and semantic placenta segmentation in a single convolutional neural network. Through the classification task the model can learn from larger and more diverse datasets while improving the accuracy of the segmentation task in particular in limited training set conditions. With this approach we investigate the variability in annotations from multiple raters and show that our automatic segmentations (Dice of 0.86 for anterior and 0.83 for posterior placentas) achieve human-level performance as compared to intra- and inter-observer variability. Lastly, our approach can deliver whole placenta segmentation using a multi-view US acquisition pipeline consisting of three stages: multi-probe image acquisition, image fusion and image segmentation. This results in high quality segmentation of larger structures such as the placenta in US with reduced image artifacts which are beyond the field-of-view of single probes.
Topics: Humans; Female; Pregnancy; Placenta
PubMed: 36257132
DOI: 10.1016/j.media.2022.102639 -
Reproductive Toxicology (Elmsford, N.Y.) Jun 2016Cannabis sativa is the most consumed illegal drug around the world. Its consumption during pregnancy is associated with gestational complications, particularly with... (Review)
Review
Cannabis sativa is the most consumed illegal drug around the world. Its consumption during pregnancy is associated with gestational complications, particularly with fetal growth restriction. Endocannabinoids (eCBs) are lipid molecules that act by activating the G-protein coupled cannabinoid receptors, which are also target of the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC). The endocannabinoid system (ECS) participates in distinct biological processes, including pain, inflammation, neuroprotection, and several reproductive events. In addition, an abnormal expression of ECS is associated with infertility and miscarriages. This manuscript will review and discuss the expression of ECS in normal and pathological human placentas, and the role of eCBs and THC in trophoblast proliferation, apoptosis, differentiation, and function. The current evidence points towards a role of ECS in human placentation, shedding light on the contribution of the eCBs in the coordination of human placentation, and in the cellular mechanisms underlying the deleterious effects of cannabis consumption during pregnancy.
Topics: Animals; Endocannabinoids; Female; Humans; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 26965993
DOI: 10.1016/j.reprotox.2016.03.002 -
Histology and Histopathology Apr 2017The placenta, which is a regulator organ for many metabolic activities between mother and fetus, is critical in influencing the outcome of pregnancy. Therefore, fetal... (Review)
Review
The placenta, which is a regulator organ for many metabolic activities between mother and fetus, is critical in influencing the outcome of pregnancy. Therefore, fetal growth is directly related to the placental development. Placental development depends on the coordinated action of trophoblast proliferation, differentiation and invasion. Studies on cell cycle related proteins that control these events are limited. Abnormal placental development is linked to various pregnancy pathologies such as preeclampsia, intrauterine growth restriction, diabetes mellitus and gestational trophoblastic diseases. The cell cycle mechanism of human placenta should be well understood for a healthy pregnancy outcome. Moreover, how cell cycle related proteins that control placental development are affected in pregnancy pathologies is not fully understood yet. Therefore, the aim of this review is to address the currently available knowledge on cell cycle regulatory proteins involved in human placental development and on the expression differences of these proteins in pathological placentas.
Topics: Cell Cycle Proteins; Female; Humans; Placenta; Placentation; Pregnancy
PubMed: 27665761
DOI: 10.14670/HH-11-832 -
Veterinary Pathology Mar 2019Bovine abortion is a worldwide problem, but despite extensive histopathologic and molecular investigations, the cause of abortion remains unclear in about 70% of cases....
Bovine abortion is a worldwide problem, but despite extensive histopathologic and molecular investigations, the cause of abortion remains unclear in about 70% of cases. Cellular debris is a commonly observed histopathologic finding in the fetal placenta and is often interpreted as necrosis. In this study, the nature of this cellular debris was characterized, and histologic changes in the normal fetal placenta during pregnancy and after delivery were assessed. In addition, the presence of the most common abortifacient pathogens in Switzerland ( Chlamydiaceae, Coxiella burnetii, Neospora caninum) was tested by polymerase chain reaction. We collected 51 placentomes and 235 cotyledons from 41 and from 50 cows, respectively. In total, cellular debris was present in 48 of 51 (94%) placentomes and in 225 of 235 (96%) cotyledons, inflammation occurred in 1 of 51 (2%) placentomes and in 46 of 235 (20%) cotyledons, vasculitis was seen in 1 of 51 (2%) placentomes and 46 of 235 (20%) cotyledons, and 18 of 51 (35%) placentomes and 181 of 235 (77%) cotyledons had mineralization. The amount of cellular debris correlated with areas of positive signals for cleaved caspase 3 and lamin A. Therefore, this finding was interpreted as an apoptotic process. In total, 10 of 50 cotyledons (20%) were positive for C. burnetii DNA, most likely representing subclinical infections. The results of our study indicate that histologic features in the fetal placenta such as cellular debris, inflammation, vasculitis, and mineralization must be considered physiological processes during pregnancy and after delivery. Therefore, their presence in placentae of aborted fetuses must be interpreted with caution and might not be necessarily linked to an infectious cause of abortion.
Topics: Animals; Caspase 3; Cattle; Chlamydiaceae; Coxiella burnetii; Female; Lamin Type A; Neospora; Placenta; Postpartum Period; Pregnancy; Real-Time Polymerase Chain Reaction
PubMed: 30355149
DOI: 10.1177/0300985818806453 -
Placenta Jan 2021Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth...
INTRODUCTION
Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth outcomes in a Canadian cohort of women living with HIV (HIV) on antiretroviral therapy (ART) from conception and HIV-uninfected (HIV) women.
METHODS
Term placentas from 94 women (40 HIV, 54 HIV) were studied. Trimmed placenta weight was collected. Placenta digital photos were used to compute morphometric parameters. Regression models investigated associations between log-transformed placenta parameters and birth outcomes.
RESULTS
We observed a trend towards lower placenta weight and smaller placenta area in the HIV group, both of which were significantly associated with small for gestational age births. HIV serostatus was associated with 6-fold (95%CI 2-20) greater odds of having placenta area in the lowest quartile (<236 cm). Cord marginality (distance from the edge) was significantly lower in the HIV group (p = 0.004), with 35% of placenta having an abnormal (marginal or velamentous) cord insertion vs. 12.5% in the HIV group (p = 0.01). Velamentous cord insertion was seen in 13% of placentas in the HIV vs. 0% in HIV group (p = 0.02). A significant correlation between cord marginality and placenta thickness was observed in the HIV group, with a more marginal cord being associated with a thicker placenta. This correlation was not observed in the HIV group. HIV placentas exposed to protease inhibitors were significantly less circular compared to the HIV group (p = 0.03).
CONCLUSION
Our data suggest that HIV/ART exposure affects placenta morphology and is associated with higher rates of abnormal cord insertion.
Topics: Adult; Anti-Retroviral Agents; Female; HIV Infections; Humans; Infant, Newborn; Placenta; Pregnancy; Umbilical Cord
PubMed: 33310298
DOI: 10.1016/j.placenta.2020.12.004 -
Ultrasound in Obstetrics & Gynecology :... Jul 2023Evidence regarding placental function in pregnancies complicated by confined placental mosaicism (CPM) is conflicting. We aimed to compare placental function between CPM...
OBJECTIVES
Evidence regarding placental function in pregnancies complicated by confined placental mosaicism (CPM) is conflicting. We aimed to compare placental function between CPM and non-CPM pregnancies prenatally and at birth. A secondary objective was to evaluate the relationship between placental function and chromosomal subtype of CPM.
METHODS
This was a retrospective study of pregnancies with CPM and control pregnancies delivered at a tertiary hospital in Denmark between 2014 and 2017. Placental volume and placental transverse relaxation time (T2*) were estimated on magnetic resonance imaging (MRI), fetal weight and uterine artery pulsatility index (UtA-PI) were estimated on ultrasound and fetoplacental ratio was assessed on MRI and at birth. These estimates of placental function were adjusted for gestational age and compared between groups using the Wilcoxon rank-sum test. Within the group of CPM pregnancies, measures of placental function were compared between those at high risk (chromosome numbers 2, 3, 7, 13 and 16) and those at low risk (chromosome numbers 5, 18 and 45X).
RESULTS
A total of 90 pregnancies were included, of which 12 had CPM and 78 were controls. MRI and ultrasound examinations were performed at a median gestational age of 32.6 weeks (interquartile range, 24.7-35.3 weeks). On MRI assessment, CPM placentae were characterized by a lower placental T2* Z-score (P = 0.004), a lower fetoplacental ratio (P = 0.03) and a higher UtA-PI Z-score (P = 0.03), compared with non-CPM placentae. At birth, the fetoplacental ratio was significantly lower (P = 0.02) and placental weight Z-score was higher (P = 0.01) in CPM pregnancies compared with non-CPM pregnancies. High-risk CPM pregnancies showed a reduced placental T2* Z-score (P = 0.003), lower birth-weight Z-score (P = 0.041), earlier gestational age at delivery (P = 0.019) and higher UtA-PI Z-score (P = 0.028) compared with low-risk CPM pregnancies. Low-risk CPM pregnancies did not differ in any of these parameters from non-CPM pregnancies.
CONCLUSIONS
CPM pregnancies are characterized by an enlarged and dysfunctional placenta. Placental function was highly related to the chromosomal type of CPM; placental dysfunction was seen predominantly in high-risk CPM pregnancies in which chromosomes 2, 3, 7, 13 or 16 were involved. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Infant; Placenta; Infant, Small for Gestational Age; Mosaicism; Retrospective Studies; Ultrasonography, Prenatal; Gestational Age; Parturition; Magnetic Resonance Imaging; Uterine Artery
PubMed: 36730148
DOI: 10.1002/uog.26174