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Nature Dec 2018The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with...
The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.
Topics: Cell Differentiation; Cell Movement; Chorionic Gonadotropin; DNA Methylation; Decidua; Female; Growth Differentiation Factor 15; HLA Antigens; Humans; Maternal-Fetal Relations; Models, Biological; Organoids; Placentation; Pregnancy; Pregnancy-Specific beta 1-Glycoproteins; Tissue Culture Techniques; Transcriptome; Trophoblasts
PubMed: 30487605
DOI: 10.1038/s41586-018-0753-3 -
Journal of Diabetes Research 2019Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially... (Review)
Review
Insulin resistance changes over time during pregnancy, and in the last half of the pregnancy, insulin resistance increases considerably and can become severe, especially in women with gestational diabetes and type 2 diabetes. Numerous factors such as placental hormones, obesity, inactivity, an unhealthy diet, and genetic and epigenetic contributions influence insulin resistance in pregnancy, but the causal mechanisms are complex and still not completely elucidated. In this review, we strive to give an overview of the many components that have been ascribed to contribute to the insulin resistance in pregnancy. Knowledge about the causes and consequences of insulin resistance is of extreme importance in order to establish the best possible treatment during pregnancy as severe insulin resistance can result in metabolic dysfunction in both mother and offspring on a short as well as long-term basis.
Topics: Adipokines; Chorionic Gonadotropin; Cytokines; Diabetes, Gestational; Diet; Epigenesis, Genetic; Estradiol; Exosomes; Female; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Gestational Age; Growth Hormone; Humans; Hydrocortisone; Insulin Resistance; Obesity, Maternal; Placenta; Placental Hormones; Placental Lactogen; Polycystic Ovary Syndrome; Pregnancy; Progesterone; Prolactin; Sedentary Behavior
PubMed: 31828161
DOI: 10.1155/2019/5320156 -
Philosophical Transactions of the Royal... Mar 2015The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are... (Review)
Review
The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain.
Topics: Female; Fetus; Humans; Placenta; Placental Circulation; Placental Hormones; Posture; Pregnancy; Vascular Remodeling
PubMed: 25602070
DOI: 10.1098/rstb.2014.0066 -
Frontiers in Endocrinology 2022
Topics: Endocrine System Diseases; Female; Humans; Placenta; Placental Hormones; Pre-Eclampsia; Pregnancy
PubMed: 35573985
DOI: 10.3389/fendo.2022.905829 -
International Journal of Molecular... Jul 2021Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic... (Review)
Review
Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic membranes and placental hormones such as chorionic gonadotrophin and placental lactogen. A comparable architecture of the intervillous space is found only in Old World monkeys and apes. The routes of trophoblast invasion and the precise role of extravillous trophoblast in uterine artery transformation is similar in chimpanzee and gorilla. Extended parental care is shared with the great apes, and though human babies are rather helpless at birth, they are well developed (precocial) in other respects. Primates and rodents last shared a common ancestor in the Cretaceous period, and their placentation has evolved independently for some 80 million years. This is reflected in many aspects of their placentation. Some apparent resemblances such as interstitial implantation and placental lactogens are the result of convergent evolution. For rodent models such as the mouse, the differences are compounded by short gestations leading to the delivery of poorly developed (altricial) young.
Topics: Animals; Biological Evolution; Female; Humans; Placenta; Placental Hormones; Placentation; Pregnancy; Primates; Uterine Artery
PubMed: 34360862
DOI: 10.3390/ijms22158099 -
The Journal of Clinical Endocrinology... Feb 2022
Topics: Breast Feeding; Female; Fluorocarbons; Humans; Lactation; Placenta; Placental Hormones; Pregnancy
PubMed: 34562075
DOI: 10.1210/clinem/dgab702 -
International Journal of Molecular... Jul 2017Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic... (Review)
Review
Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all original research articles on the role of HCG in breast cancer were considered, which are listed in PubMed database and were written in English. The role of HCG in breast cancer seems to be a paradox. Placental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition. On the other hand, ectopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function. Placental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis. Therefore, mimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention, whereas targeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy.
Topics: Apoptosis; Breast Neoplasms; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Genomic Imprinting; Humans; Placenta; Pregnancy
PubMed: 28754015
DOI: 10.3390/ijms18071587 -
Frontiers in Endocrinology 2022Human placenta secretes a variety of hormones, some of them in large amounts. Their effects on maternal physiology, including the immune system, are poorly understood.... (Review)
Review
Human placenta secretes a variety of hormones, some of them in large amounts. Their effects on maternal physiology, including the immune system, are poorly understood. Not one of the protein hormones specific to human placenta occurs outside primates. Instead, laboratory and domesticated species have their own sets of placental hormones. There are nonetheless several examples of convergent evolution. Thus, horse and human have chorionic gonadotrophins with similar functions whilst pregnancy-specific glycoproteins have evolved in primates, rodents, horses, and some bats, perhaps to support invasive placentation. Placental lactogens occur in rodents and ruminants as well as primates though evolved through duplication of different genes and with functions that only partially overlap. There are also placental hormones, such as the pregnancy-associated glycoproteins of ruminants, that have no equivalent in human gestation. This review focusses on the evolution of placental hormones involved in recognition and maintenance of pregnancy, in maternal adaptations to pregnancy and lactation, and in facilitating immune tolerance of the fetal semiallograft. The contention is that knowledge gained from laboratory and domesticated mammals can translate to a better understanding of human placental endocrinology, but only if viewed in an evolutionary context.
Topics: Animals; Female; Glycoproteins; Horses; Humans; Models, Animal; Placenta; Placental Hormones; Placentation; Pregnancy; Rodentia
PubMed: 35692413
DOI: 10.3389/fendo.2022.891927 -
Clinical Chemistry and Laboratory... Dec 2020
Topics: Chorionic Gonadotropin; Female; Humans; Pregnancy; Pregnancy Tests
PubMed: 33554533
DOI: 10.1515/cclm-2020-1797 -
International Journal of Molecular... Dec 2022Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to... (Meta-Analysis)
Meta-Analysis Review
Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to maternal and fetal outcomes, yet-despite human observational data spanning several decades-evidence on the role and importance of this hormone remains disparate and conflicting. We aimed to explore (via systematic review and meta-analysis) the relationship between hPL levels, maternal pre-existing and gestational metabolic conditions, and fetal growth. MEDLINE via OVID, CINAHL plus, and Embase were searched from inception through 9 May 2022. Eligible studies included women who were pregnant or up to 12 months post-partum, and reported at least one endogenous maternal serum hPL level during pregnancy in relation to pre-specified metabolic outcomes. Two independent reviewers extracted data. Meta-analysis was conducted where possible; for other outcomes narrative synthesis was performed. 35 studies met eligibility criteria. No relationship was noted between hPL and gestational diabetes status. In type 1 diabetes mellitus, hPL levels appeared lower in early pregnancy (possibly reflecting delayed placental development) and higher in late pregnancy (possibly reflecting increased placental mass). Limited data were found in other pre-existing metabolic conditions. Levels of hPL appear to be positively related to placental mass and infant birthweight in pregnancies affected by maternal diabetes. The relationship between hPL, a purported pregnancy metabolic hormone, and maternal metabolism in human pregnancy is complex and remains unclear. This antenatal biomarker may offer value, but future studies in well-defined contemporary populations are required.
Topics: Pregnancy; Female; Humans; Placental Lactogen; Placenta; Placental Hormones; Fetal Development; Biomarkers
PubMed: 36555258
DOI: 10.3390/ijms232415621