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Human Reproduction Update May 2019Initially identified as suppressors of metastasis in various types of cancer, kisspeptins are a family of neuropeptides that are key regulators of the mammalian... (Review)
Review
BACKGROUND
Initially identified as suppressors of metastasis in various types of cancer, kisspeptins are a family of neuropeptides that are key regulators of the mammalian reproductive axis. Accumulating evidence has shown that kisspeptin is able to control both the pulsatile and surge GnRH release, playing fundamental roles in female reproduction, which include the secretion of gonadotropins, puberty onset, brain sex differentiation, ovulation and the metabolic regulation of fertility. Furthermore, recent studies have demonstrated the involvement of the kisspeptin system in the processes of implantation and placentation. This review summarizes the current knowledge of the pathophysiological role and utility of these local placental regulatory factors as potential biomarkers during the early human gestation.
OBJECTIVE AND RATIONALE
A successful pregnancy, from the initiation of embryo implantation to parturition, is a complex process that requires the orchestration of a series of events. This review aims to concisely summarize what is known about the role of the kisspeptin system in implantation, placentation, early human pregnancy and pregnancy-related disorders, and to develop strategies for predicting, diagnosing and treating these abnormalities.
SEARCH METHODS
Using the PubMed and Google Scholar databases, we performed comprehensive literature searches in the English language describing the advancement of kisspeptins and the kisspeptin receptor (KISS1R) in implantation, placentation and early pregnancy in humans, since its initial identification in 1996 and ending in July 2018.
OUTCOMES
Recent studies have shown the coordinated spatial and temporal expression patterns of kisspeptins and KISS1R during human pregnancy. The experimental data gathered recently suggest putative roles of kisspeptin signaling in the regulation of trophoblast invasion, embryo implantation, placentation and early pregnancy. Dysregulation of the kisspeptin system may negatively affect the processes of implantation as well as placentation. Clinical studies indicate that the circulating levels of kisspeptins or the expression levels of kisspeptin/KISS1R in the placental tissues may be used as potential diagnostic markers for women with miscarriage and gestational trophoblastic neoplasia.
WIDER IMPLICATIONS
Comprehensive research on the pathophysiological role of the kisspeptin/KISS1R system in implantation and placentation will provide a dynamic and powerful approach to understanding the processes of early pregnancy, with potential applications in observational and analytic screening as well as the diagnosis, prognosis and treatment of implantation failure and early pregnancy-related disorders.
Topics: Animals; Embryo Implantation; Female; Fertility; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Ovulation; Placenta; Placentation; Pregnancy; Receptors, Kisspeptin-1; Reproduction; Signal Transduction
PubMed: 30649364
DOI: 10.1093/humupd/dmy046 -
Frontiers in Immunology 2024The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide... (Review)
Review
The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide nutrients, gases, and hormones to the developing fetus. The placenta has endocrine functions, orchestrates maternal adaptations to pregnancy at different periods of pregnancy, and acts as a selective barrier to minimize exposure of developing fetus to xenobiotics, pathogens, and parasites. Despite the fact that this ancient organ is central for establishment of a normal pregnancy in eutherians, the placenta remains one of the least studied organs. The first step of pregnancy, embryo implantation, is finely regulated by the trophoectoderm, the precursor of all trophoblast cells. There is a bidirectional communication between placenta and endometrium leading to decidualization, a critical step for maintenance of pregnancy. There are three-direction interactions between the placenta, maternal immune cells, and the endometrium for adaptation of endometrial immune system to the allogeneic fetus. While 65% of all systemically expressed human proteins have been found in the placenta tissues, it expresses numerous placenta-specific proteins, whose expression are dramatically changed in gestational diseases and could serve as biomarkers for early detection of gestational diseases. Surprisingly, placentation and carcinogenesis exhibit numerous shared features in metabolism and cell behavior, proteins and molecular signatures, signaling pathways, and tissue microenvironment, which proposes the concept of "cancer as ectopic trophoblastic cells". By extensive researches in this novel field, a handful of cancer biomarkers has been discovered. This review paper, which has been inspired in part by our extensive experiences during the past couple of years, highlights new aspects of placental functions with emphasis on its immunomodulatory role in establishment of a successful pregnancy and on a potential link between placentation and carcinogenesis.
Topics: Humans; Pregnancy; Female; Placenta; Animals; Placentation; Endometrium; Neoplasms; Embryo Implantation
PubMed: 38707901
DOI: 10.3389/fimmu.2024.1385762 -
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 -
Reproductive Biology and Endocrinology... Mar 2012hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists... (Review)
Review
BACKGROUND
hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail.
CONTENT
These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies.
CONCLUSIONS
The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death.
Topics: Chorionic Gonadotropin; Female; Glycosylation; Humans; Menstrual Cycle; Molecular Structure; Neoplasms; Placenta; Placentation; Pregnancy; Sulfates; Trophoblasts
PubMed: 22455390
DOI: 10.1186/1477-7827-10-24 -
Pflugers Archiv : European Journal of... Jul 2023Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally... (Review)
Review
Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally defined as hypertension and may be accompanied by other end organ damages including proteinuria, maternal organ disturbances including renal insufficiency, neurological complications, thrombocytopenia, impaired liver function, or uteroplacental dysfunction such as fetal growth restriction and stillbirth. Although the causes of these hypertensive disorders of pregnancy are multifactorial and elusive, they seem to share some common vascular-related mechanisms, including diseased spiral arteries, placental ischemia, and endothelial dysfunction. Recently, preeclampsia is being considered as a vascular disorder. Unfortunately, due to the complex etiology of preeclampsia and safety concerns on drug usage during pregnancy, there is still no effective pharmacological treatments available for preeclampsia yet. An emerging area of interest in this research field is the potential beneficial effects of dietary intervention on reducing the risk of preeclampsia. Recent studies have been focused on the association between deficiencies or excesses of some nutrients and complications during pregnancy, fetal growth and development, and later risk of cardiovascular and metabolic diseases in the offspring. In this review, we discuss the involvement of placental vascular dysfunction in preeclampsia. We summarize the current understanding of the association between abnormal placentation and preeclampsia in a vascular perspective. Finally, we evaluate several studied dietary supplementations to prevent and reduce the risk of preeclampsia, targeting placental vascular development and function, leading to improved pregnancy and postnatal outcomes.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Placenta; Hypertension, Pregnancy-Induced; Placentation; Dietary Supplements
PubMed: 37043045
DOI: 10.1007/s00424-023-02810-2 -
International Journal of Molecular... Mar 2022The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-guided uterine spiral artery remodeling, which resembles... (Review)
Review
The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-guided uterine spiral artery remodeling, which resembles human placentation. Uterine spiral arteries are extensively remodeled to deliver sufficient supply of maternal blood and nutrients to the developing fetus. Inadequacies in these key processes negatively impact fetal growth and development. Recent innovations in genome editing combined with effective phenotyping strategies have provided new insights into placental development. Application of these research approaches has highlighted both conserved and species-specific features of hemochorial placentation. The review provides foundational information on rat hemochorial placental development and function during physiological and pathological states, especially as related to the invasive trophoblast cell-guided transformation of uterine spiral arteries. Our goal is to showcase the utility of the rat as a model for in vivo mechanistic investigations targeting regulatory events within the uterine-placental interface.
Topics: Animals; Female; Placenta; Placentation; Pregnancy; Rats; Trophoblasts; Uterine Artery; Uterus
PubMed: 35328368
DOI: 10.3390/ijms23062947 -
Free Radical Biology & Medicine Mar 2019As the interface between the fetal and maternal circulation, the placenta facilitates both nutrient and waste exchange for the developing fetus. Iron is essential for... (Review)
Review
As the interface between the fetal and maternal circulation, the placenta facilitates both nutrient and waste exchange for the developing fetus. Iron is essential for healthy pregnancy, and transport of iron across the placenta is required for fetal growth and development. Perturbation of this transfer can lead to adverse pregnancy outcomes. Despite its importance, our understanding of how a large amount of iron is transported across placental membranes, how this process is regulated, and which iron transporter proteins function in different placental cells remains rudimentary. Mechanistic studies in mouse models, including placenta-specific deletion or overexpression of iron-related proteins will be essential to make progress. This review summarizes our current understanding about iron transport across the syncytiotrophoblast under physiological conditions and identifies areas for further investigation.
Topics: Animals; Biological Transport; Female; Fetal Development; Fetus; Humans; Ion Transport; Iron; Mice; Placenta; Placentation; Pregnancy
PubMed: 29981833
DOI: 10.1016/j.freeradbiomed.2018.07.001 -
Developmental Cell Jun 2017Many of the hundreds of KRAB zinc finger proteins encoded by human and mouse are involved in taming the transcriptional regulatory potential of transposable elements.... (Review)
Review
Many of the hundreds of KRAB zinc finger proteins encoded by human and mouse are involved in taming the transcriptional regulatory potential of transposable elements. Reporting recently in Science, Yang et al. (2017) reveal that one murine family member, ZFP568, controls Igf2 expression for proper embryonic and placental development.
Topics: Animals; Embryonic Development; Female; Gene Expression Regulation; Humans; Placenta; Placentation; Pregnancy; Repressor Proteins; Zinc Fingers
PubMed: 28633014
DOI: 10.1016/j.devcel.2017.06.005 -
Comprehensive Physiology Jun 2021Successful pregnancy and reproduction are dependent on adequate uterine blood flow, placental perfusion, and vascular responsivity to fetal demands. The ability to...
Successful pregnancy and reproduction are dependent on adequate uterine blood flow, placental perfusion, and vascular responsivity to fetal demands. The ability to support pregnancy centers on systemic adaptation and endometrial preparation through decidualization, embryonic implantation, trophoblast invasion, arterial/arteriolar reactivity, and vascular remodeling. These adaptations occur through responsiveness to endocrine signaling and local uteroplacental mediators. The purpose of this article is to highlight the current knowledge associated with vascular remodeling and responsivity during uterine preparation for and during pregnancy. We focus on maternal cardiovascular systemic and uterine modifications, endometrial decidualization, implantation and invasion, uterine and spiral artery remodeling, local uterine regulatory mechanisms, placentation, and pathological consequences of vascular dysfunction during pregnancy. © 2021 American Physiological Society. Compr Physiol 11:1-23, 2021.
Topics: Female; Humans; Placenta; Placental Circulation; Placentation; Pregnancy; Trophoblasts; Vascular Remodeling
PubMed: 34061977
DOI: 10.1002/cphy.c190015 -
Human Reproduction Update Oct 2021Stanniocalcin-1 (STC-1) is a widely expressed glycoprotein hormone involved in a diverse spectrum of physiological and pathophysiological processes including... (Review)
Review
BACKGROUND
Stanniocalcin-1 (STC-1) is a widely expressed glycoprotein hormone involved in a diverse spectrum of physiological and pathophysiological processes including angiogenesis, mineral homeostasis, cell proliferation, inflammation and apoptosis. Over the last 20 years, numerous studies have reported STC-1 expression within female reproductive tissues including the uterus, ovaries and placenta and implicated STC-1 in processes such as ovarian follicular development, blastocyst implantation, vascular remodelling in early pregnancy and placental development. Notably, dysregulation of STC-1 within reproductive tissues has been linked to the onset of severe reproductive disorders including endometriosis, polycystic ovary syndrome, poor trophoblast invasion and placental perfusion in early pregnancy. Furthermore, significant changes in tissue expression and in maternal systemic concentration take place throughout pregnancy and further substantiate the vital role of this protein in reproductive health and disease.
OBJECTIVE AND RATIONALE
Our aim is to provide a comprehensive overview of the existing literature, to summarise the expression profile and roles of STC-1 within the female reproductive system and its associated pathologies. We highlight the gaps in the current knowledge and suggest potential avenues for future research.
SEARCH METHODS
Relevant studies were identified through searching the PubMed database using the following search terms: 'stanniocalcin-1', 'placenta', 'ovary', 'endometrium', 'pregnancy', 'reproduction', 'early gestation'. Only English language papers published between 1995 and 2020 were included.
OUTCOMES
This review provides compelling evidence of the vital function that STC-1 plays within the female reproductive system. The literature presented summarise the wide expression profile of STC-1 within female reproductive organs, as well as highlighting the putative roles of STC-1 in various functions in the reproductive system. Moreover, the observed link between altered STC-1 expression and the onset of various reproductive pathologies is presented, including those in pregnancy whose aetiology occurs in the first trimester. This summary emphasises the requirement for further studies on the mechanisms underlying the regulation of STC-1 expression and function.
WIDER IMPLICATIONS
STC-1 is a pleiotropic hormone involved in the regulation of a number of important biological functions needed to maintain female reproductive health. There is also growing evidence that dysregulation of STC-1 is implicated in common reproductive and obstetric disorders. Greater understanding of the physiology and biochemistry of STC-1 within the field may therefore identify possible targets for therapeutic intervention and/or diagnosis.
Topics: Endometrium; Female; Glycoproteins; Humans; Placenta; Placentation; Pregnancy
PubMed: 34432025
DOI: 10.1093/humupd/dmab028