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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 -
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 -
Placenta Jun 2015The placenta performs a wide range of physiological functions; insufficiencies in these functions may result in a variety of severe prenatal and postnatal syndromes with... (Review)
Review
The placenta performs a wide range of physiological functions; insufficiencies in these functions may result in a variety of severe prenatal and postnatal syndromes with long-term negative impacts on human adult health. Recent advances in magnetic resonance imaging (MRI) studies of placental function, in both animal models and humans, have contributed significantly to our understanding of placental structure, blood flow, oxygenation status, and metabolic profile, and have provided important insights into pregnancy complications.
Topics: Animals; Female; Humans; Magnetic Resonance Imaging; Placenta; Pregnancy; Pregnancy Complications
PubMed: 25916594
DOI: 10.1016/j.placenta.2015.04.003 -
Ultrasound in Medicine & Biology Jan 2023Ultrasound-based assistive tools are aimed at reducing the high skill needed to interpret a scan by providing automatic image guidance. This may encourage uptake of...
Ultrasound-based assistive tools are aimed at reducing the high skill needed to interpret a scan by providing automatic image guidance. This may encourage uptake of ultrasound (US) clinical assessments in rural settings in low- and middle-income countries (LMICs), where well-trained sonographers can be scarce. This paper describes a new method that automatically generates an assistive video overlay to provide image guidance to a user to assess placenta location. The user captures US video by following a sweep protocol that scans a U-shape on the lower maternal abdomen. The sweep trajectory is simple and easy to learn. We initially explore a 2-D embedding of placenta shapes, mapping manually segmented placentas in US video frames to a 2-D space. We map 2013 frames from 11 videos. This provides insight into the spectrum of placenta shapes that appear when using the sweep protocol. We propose classification of the placenta shapes from three observed clusters: complex, tip and rectangular. We use this insight to design an effective automatic segmentation algorithm, combining a U-Net with a CRF-RNN module to enhance segmentation performance with respect to placenta shape. The U-Net + CRF-RNN algorithm automatically segments the placenta and maternal bladder. We assess segmentation performance using both area and shape metrics. We report results comparable to the state-of-the-art for automatic placenta segmentation on the Dice metric, achieving 0.83 ± 0.15 evaluated on 2127 frames from 10 videos. We also qualitatively evaluate 78,308 frames from 135 videos, assessing if the anatomical outline is correctly segmented. We found that addition of the CRF-RNN improves over a baseline U-Net when faced with a complex placenta shape, which we observe in our 2-D embedding, up to 14% with respect to the percentage shape error. From the segmentations, an assistive video overlay is automatically constructed that (i) highlights the placenta and bladder, (ii) determines the lower placenta edge and highlights this location as a point and (iii) labels a 2-cm clearance on the lower placenta edge. The 2-cm clearance is chosen to satisfy current clinical guidelines. We propose to assess the placenta location by comparing the 2-cm region and the bottom of the bladder, which represents a coarse localization of the cervix. Anatomically, the bladder must sit above the cervix region. We present proof-of-concept results for the video overlay.
Topics: Pregnancy; Female; Humans; Image Processing, Computer-Assisted; Ultrasonography; Algorithms; Urinary Bladder; Placenta
PubMed: 36241588
DOI: 10.1016/j.ultrasmedbio.2022.08.006 -
International Journal of Environmental... Sep 2022Microplastics (MPs) are defined as plastic particles smaller than 5 mm. They have been found almost everywhere they have been searched for and recent discoveries have...
Microplastics (MPs) are defined as plastic particles smaller than 5 mm. They have been found almost everywhere they have been searched for and recent discoveries have also demonstrated their presence in human placenta, blood, meconium, and breastmilk, but their location and toxicity to humans have not been reported to date. The aim of this study was twofold: 1. To locate MPs within the intra/extracellular compartment in human placenta. 2. To understand whether their presence and location are associated with possible structural changes of cell organelles. Using variable pressure scanning electron microscopy and transmission electron microscopy, MPs have been localized in ten human placentas. In this study, we demonstrated for the first time the presence and localization in the cellular compartment of fragments compatible with MPs in the human placenta and we hypothesized a possible correlation between their presence and important ultrastructural alterations of some intracytoplasmic organelles (mitochondria and endoplasmic reticulum). These alterations have never been reported in normal healthy term pregnancies until today. They could be the result of a prolonged attempt to remove and destroy the plastic particles inside the placental tissue. The presence of virtually indestructible particles in term human placenta could contribute to the activation of pathological traits, such as oxidative stress, apoptosis, and inflammation, characteristic of metabolic disorders underlying obesity, diabetes, and metabolic syndrome and partially accounting for the recent epidemic of non-communicable diseases.
Topics: Female; Humans; Infant, Newborn; Meconium; Microplastics; Microscopy, Electron, Transmission; Placenta; Plastics; Pregnancy
PubMed: 36141864
DOI: 10.3390/ijerph191811593 -
International Journal of Molecular... Oct 2023Today, there is strong and diversified evidence that in humans at least 50% of early embryos do not proceed beyond the pre-implantation period. This evidence comes from... (Review)
Review
Today, there is strong and diversified evidence that in humans at least 50% of early embryos do not proceed beyond the pre-implantation period. This evidence comes from clinical investigations, demography, epidemiology, embryology, immunology, and molecular biology. The purpose of this article is to highlight the steps leading to the establishment of pregnancy and placenta formation. These early events document the existence of a clear distinction between embryonic losses during the first two weeks after conception and those occurring during the subsequent months. This review attempts to highlight the nature of the maternal-embryonic dialogue and the major mechanisms active during the pre-implantation period aimed at "selecting" embryos with the ability to proceed to the formation of the placenta and therefore to the completion of pregnancy. This intense molecular cross-talk between the early embryo and the endometrium starts even before the blastocyst reaches the uterine cavity, substantially initiating and conditioning the process of implantation and the formation of the placenta. Today, several factors involved in this dialogue have been identified, although the best-known and overall, the most important, still remains , indispensable during the first 8 to 10 weeks after fertilization. In addition, there are other substances acting during the first days following fertilization, the , believed to be involved in the suppression of the maternal response, thereby allowing the continued viability of the early embryo. The secreted between 2 and 4 days after fertilization. This linear peptide molecule exhibits a self-protective and antitoxic action, is present in maternal blood as early as 7 days after conception, and is absent in the presence of non-viable embryos. The , produced and released by embryos of all mammalian species studied seems to have a role in the ligand-mediated trophic support of the early embryo. The implantation process is also guided by signals from cells in the decidualized endometrium. Various types of cells are involved, among them epithelial, stromal, and trophoblastic, producing a number of cellular molecules, such as cytokines, chemokines, growth factors, and adhesion molecules. Immune cells are also involved, mainly uterine natural killer cells, macrophages, and T cells. In conclusion, events taking place during the first two weeks after fertilization determine whether pregnancy can proceed and therefore whether placenta's formation can proceed. These events represent the scientific basis for a clear distinction between the first two weeks following fertilization and the rest of gestation. For this reason, we propose that a new nomenclature be adopted specifically separating the two periods. In other words, the period from fertilization and birth should be named "gestation", whereas that from the completion of the process of implantation leading to the formation of the placenta, and birth should be named "pregnancy".
Topics: Animals; Humans; Pregnancy; Female; Placenta; Embryo Implantation; Endometrium; Uterus; Embryo, Mammalian; Mammals
PubMed: 37895099
DOI: 10.3390/ijms242015420 -
Topics in Magnetic Resonance Imaging :... Oct 2019The Human Placenta Project has focused attention on the need for noninvasive magnetic resonance imaging (MRI)-based techniques to diagnose and monitor placental function... (Review)
Review
The Human Placenta Project has focused attention on the need for noninvasive magnetic resonance imaging (MRI)-based techniques to diagnose and monitor placental function throughout pregnancy. The hope is that the management of placenta-related pathologies would be improved if physicians had more direct, real-time measures of placental health to guide clinical decision making. As oxygen alters signal intensity on MRI and oxygen transport is a key function of the placenta, many of the MRI methods under development are focused on quantifying oxygen transport or oxygen content of the placenta. For example, measurements from blood oxygen level-dependent imaging of the placenta during maternal hyperoxia correspond to outcomes in twin pregnancies, suggesting that some aspects of placental oxygen transport can be monitored by MRI. Additional methods are being developed to accurately quantify baseline placental oxygenation by MRI relaxometry. However, direct validation of placental MRI methods is challenging and therefore animal studies and ex vivo studies of human placentas are needed. Here we provide an overview of the current state of the art of oxygen transport and quantification with MRI. We suggest that as these techniques are being developed, increased focus be placed on ensuring they are robust and reliable across individuals and standardized to enable predictive diagnostic models to be generated from the data. The field is still several years away from establishing the clinical benefit of monitoring placental function in real time with MRI, but the promise of individual personalized diagnosis and monitoring of placental disease in real time continues to motivate this effort.
Topics: Animals; Female; Humans; Hyperoxia; Magnetic Resonance Imaging; Oxygen; Placenta; Pregnancy
PubMed: 31592995
DOI: 10.1097/RMR.0000000000000221 -
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 -
Biology of Sex Differences Sep 2022The fetal placenta is a source of hormones and immune factors that play a vital role in maintaining pregnancy and facilitating fetal growth. Cells in this extraembryonic... (Review)
Review
The fetal placenta is a source of hormones and immune factors that play a vital role in maintaining pregnancy and facilitating fetal growth. Cells in this extraembryonic compartment match the chromosomal sex of the embryo itself. Sex differences have been observed in common gestational pathologies, highlighting the importance of maternal immune tolerance to the fetal compartment. Over the past decade, several studies examining placentas from term pregnancies have revealed widespread sex differences in hormone signaling, immune signaling, and metabolic functions. Given the rapid and dynamic development of the human placenta, sex differences that exist at term (37-42 weeks gestation) are unlikely to align precisely with those present at earlier stages when the fetal-maternal interface is being formed and the foundations of a healthy or diseased pregnancy are established. While fetal sex as a variable is often left unreported in studies performing transcriptomic profiling of the first-trimester human placenta, four recent studies have specifically examined fetal sex in early human placental development. In this review, we discuss the findings from these publications and consider the evidence for the genetic, hormonal, and immune mechanisms that are theorized to account for sex differences in early human placenta. We also highlight the cellular and molecular processes that are most likely to be impacted by fetal sex and the evolutionary pressures that may have given rise to these differences. With growing recognition of the fetal origins of health and disease, it is important to shed light on sex differences in early prenatal development, as these observations may unlock insight into the foundations of sex-biased pathologies that emerge later in life.
Topics: Female; Fetal Development; Gestational Age; Hormones; Humans; Male; Placenta; Pregnancy; Sex Characteristics
PubMed: 36114567
DOI: 10.1186/s13293-022-00459-7 -
Frontiers in Cellular and Infection... 2023is a ubiquitous apicomplexan parasite that can infect virtually any warm-blooded animal. Acquired infection during pregnancy and the placental breach, is at the core of... (Review)
Review
is a ubiquitous apicomplexan parasite that can infect virtually any warm-blooded animal. Acquired infection during pregnancy and the placental breach, is at the core of the most devastating consequences of toxoplasmosis. can severely impact the pregnancy's outcome causing miscarriages, stillbirths, premature births, babies with hydrocephalus, microcephaly or intellectual disability, and other later onset neurological, ophthalmological or auditory diseases. To tackle vertical transmission, it is important to understand the mechanisms underlying host-parasite interactions at the maternal-fetal interface. Nonetheless, the complexity of the human placenta and the ethical concerns associated with its study, have narrowed the modeling of parasite vertical transmission to animal models, encompassing several unavoidable experimental limitations. Some of these difficulties have been overcome by the development of different human cell lines and a variety of primary cultures obtained from human placentas. These cellular models, though extremely valuable, have limited ability to recreate what happens . During the last decades, the development of new biomaterials and the increase in stem cell knowledge have led to the generation of more physiologically relevant models. These cell cultures incorporate new dimensions and cellular diversity, emerging as promising tools for unraveling the poorly understood ´s infection mechanisms during pregnancy. Herein, we review the state of the art of 2D and 3D cultures to approach the biology of pertaining to vertical transmission, highlighting the challenges and experimental opportunities of these up-and-coming experimental platforms.
Topics: Animals; Humans; Pregnancy; Female; Placenta; Toxoplasma; Toxoplasmosis; Infectious Disease Transmission, Vertical; Models, Animal
PubMed: 36968102
DOI: 10.3389/fcimb.2023.1130901