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International Journal of Molecular... Dec 2022Thyroid hormone is essential for fetal (brain) development. Plasma membrane transporters control the intracellular bioavailability of thyroid hormone. In the past few... (Review)
Review
Thyroid hormone is essential for fetal (brain) development. Plasma membrane transporters control the intracellular bioavailability of thyroid hormone. In the past few decades, 15 human thyroid hormone transporters have been identified, and among them, mutations in monocarboxylate transporter (MCT)8 and organic anion transporting peptide (OATP)1C1 are associated with clinical phenotypes. Different animal and human models have been employed to unravel the (patho)-physiological role of thyroid hormone transporters. However, most studies on thyroid hormone transporters focus on postnatal development. This review summarizes the research on the thyroid hormone transporters in pregnancy and fetal development, including their substrate preference, expression and tissue distribution, and physiological and pathophysiological role in thyroid homeostasis and clinical disorders. As the fetus depends on the maternal thyroid hormone supply, especially during the first half of pregnancy, the review also elaborates on thyroid hormone transport across the human placental barrier. Future studies may reveal how the different transporters contribute to thyroid hormone homeostasis in fetal tissues to properly facilitate development. Employing state-of-the-art human models will enable a better understanding of their roles in thyroid hormone homeostasis.
Topics: Animals; Female; Humans; Pregnancy; Monocarboxylic Acid Transporters; Symporters; Placenta; Thyroid Hormones; Fetal Development; Organic Anion Transporters
PubMed: 36499435
DOI: 10.3390/ijms232315113 -
Clinical Chemistry and Laboratory... Dec 2020
Topics: Chorionic Gonadotropin; Female; Humans; Pregnancy; Pregnancy Tests
PubMed: 33554533
DOI: 10.1515/cclm-2020-1797 -
Cell Proliferation May 2023The placental barrier plays a key role in protecting the developing fetus from xenobiotics and exchanging substances between the fetus and mother. However, the...
The placental barrier plays a key role in protecting the developing fetus from xenobiotics and exchanging substances between the fetus and mother. However, the trophoblast cell lines and animal models are often inadequate to recapitulate the key architecture and functional characteristics of human placental barrier. Here, we described a biomimetic placental barrier model from human trophoblast stem cells (hTSCs) in a perfused organ chip system. The placental barrier was constructed by co-culture of hTSCs and endothelial cells on the opposite sides of a collagen-coated membrane on chip. hTSCs can differentiate into cytotrophoblasts (CT) and syncytiotrophoblast (ST), which self-assembled into bilayered trophoblastic epithelium with placental microvilli-like structure under dynamic cultures. The formed placental barrier displayed dense microvilli, higher level secretion of human chorionic gonadotropin (hCG), enhanced glucose transport activity. Moreover, RNA-seq analysis revealed upregulated ST expression and activation of trophoblast differentiation-related signalling pathways. These results indicated the key role of fluid flow in promoting trophoblast syncytialization and placental early development. After exposure to mono-2-ethylhexyl phthalate, one of the endocrine disrupting chemicals, the model showed inhibited hCG production and disturbed ST formation in trophoblastic epithelium, suggesting impaired placental structure and function elicited by environmental toxicants. Collectively, the hTSCs-derived placental model can recapitulate placenta physiology and pathological response to external stimuli in a biomimetic manner, which is useful for the study of placental biology and associated diseases.
Topics: Animals; Humans; Pregnancy; Female; Placenta; Trophoblasts; Microphysiological Systems; Endothelial Cells; Chorionic Gonadotropin; Cell Differentiation; Stem Cells
PubMed: 37199016
DOI: 10.1111/cpr.13469 -
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 -
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 -
Apelin, APJ, and ELABELA: Role in Placental Function, Pregnancy, and Foetal Development-An Overview.Cells Dec 2021The apelinergic system, which includes the apelin receptor (APJ) as well as its two specific ligands, namely apelin and ELABELA (ELA/APELA/Toddler), have been the... (Review)
Review
The apelinergic system, which includes the apelin receptor (APJ) as well as its two specific ligands, namely apelin and ELABELA (ELA/APELA/Toddler), have been the subject of many recent studies due to their pleiotropic effects in humans and other animals. Expression of these factors has been investigated in numerous tissues and organs-for example, the lungs, heart, uterus, and ovary. Moreover, a number of studies have been devoted to understanding the role of apelin and the entire apelinergic system in the most important processes in the body, starting from early stages of human life with regulation of placental function and the proper course of pregnancy. Disturbances in the balance of placental processes such as proliferation, apoptosis, angiogenesis, or hormone secretion may lead to specific pregnancy pathologies; therefore, there is a great need to search for substances that would help in their early diagnosis or treatment. A number of studies have indicated that compounds of the apelinergic system could serve this purpose. Hence, in this review, we summarized the most important reports about the role of apelin and the entire apelinergic system in the regulation of placental physiology and pregnancy.
Topics: Amino Acid Sequence; Animals; Apelin; Apelin Receptors; Female; Fetus; Humans; Models, Biological; Peptide Hormones; Placenta; Pregnancy
PubMed: 35011661
DOI: 10.3390/cells11010099 -
Frontiers in Endocrinology 2023Endocrine-disrupting chemicals (EDCs) or endocrine disruptors are substances that are either naturally occurring or artificial and are released into the natural... (Review)
Review
Endocrine-disrupting chemicals (EDCs) or endocrine disruptors are substances that are either naturally occurring or artificial and are released into the natural environment. Humans are exposed to EDCs through ingestion, inhalation, and skin contact. Many everyday household items, such as plastic bottles and containers, the liners of metal food cans, detergents, flame retardants, food, gadgets, cosmetics, and pesticides, contain endocrine disruptors. Each hormone has a unique chemical makeup and structural attributes. The way that endocrine hormones connect to receptors is described as a "lock and key" mechanism, with each hormone serving as the key (lock). This mechanism is enabled by the complementary shape of receptors to their hormone, which allows the hormone to activate the receptors. EDCs are described as exogenous chemicals or compounds that have a negative impact on organisms' health by interacting with the functioning of the endocrine system. EDCs are associated with cancer, cardiovascular risk, behavioural disorders, autoimmune abnormalities, and reproductive disorders. EDCs exposure in humans is highly harmful during critical life stages. Nonetheless, the effect of EDCs on the placenta is often underestimated. The placenta is especially sensitive to EDCs due to its abundance of hormone receptors. In this review, we evaluated the most recent data on the effects of EDCs on placental development and function, including heavy metals, plasticizers, pesticides, flame retardants, UV filters and preservatives. The EDCs under evaluation have evidence from human biomonitoring and are found in nature. Additionally, this study indicates important knowledge gaps that will direct future research on the topic.
Topics: Pregnancy; Humans; Female; Placentation; Placenta; Endocrine Disruptors; Flame Retardants; Pesticides; Hormones
PubMed: 36896182
DOI: 10.3389/fendo.2023.1059854 -
International Journal of Molecular... Sep 2021Gonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of... (Review)
Review
Gonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of ovarian follicles, luteinizing hormone (LH) regulates preovulatory maturation of oocytes, ovulation, and formation of corpus luteum. Cognate receptors of FSH and LH are G-protein coupled receptors that predominantly signal through cAMP-dependent and cAMP-independent mechanisms that activate protein kinases. Subsequent vital steps in response to gonadotropins are mediated through activation or inhibition of transcription factors required for follicular gene expression. Estrogen receptors, classical ligand-activated transcriptional regulators, play crucial roles in regulating gonadotropin secretion from the hypothalamic-pituitary axis as well as gonadotropin function in the target organs. In this review, we discuss the role of estrogen receptor β (ERβ) regulating gonadotropin response during folliculogenesis. Ovarian follicles in Erβ knockout (Erβ) mutant female mice and rats cannot develop beyond the antral state, lack oocyte maturation, and fail to ovulate. Theca cells (TCs) in ovarian follicles express LH receptor, whereas granulosa cells (GCs) express both FSH receptor (FSHR) and LH receptor (LHCGR). As oocytes do not express the gonadotropin receptors, the somatic cells play a crucial role during gonadotropin induced oocyte maturation. Somatic cells also express high levels of estrogen receptors; while TCs express ERα and are involved in steroidogenesis, GCs express ERβ and are involved in both steroidogenesis and folliculogenesis. GCs are the primary site of ERβ-regulated gene expression. We observed that a subset of gonadotropin-induced genes in GCs, which are essential for ovarian follicle development, oocyte maturation and ovulation, are dependent on ERβ. Thus, ERβ plays a vital role in regulating the gonadotropin responses in ovary.
Topics: Animals; Chorionic Gonadotropin; Estrogen Receptor beta; Female; Follicle Stimulating Hormone; Granulosa Cells; Humans; Mice; Mice, Knockout; Rats; Theca Cells
PubMed: 34638689
DOI: 10.3390/ijms221910348 -
Evolution, Medicine, and Public Health 2022We hypothesize that some placental hormones-specifically those that arise by tandem duplication of genes for maternal hormones-may behave as gestational drivers, selfish...
We hypothesize that some placental hormones-specifically those that arise by tandem duplication of genes for maternal hormones-may behave as gestational drivers, selfish genetic elements that encourage the spontaneous abortion of offspring that fail to inherit them. Such drivers are quite simple to evolve, requiring just three things: a decrease in expression or activity of some essential maternal hormone during pregnancy; a compensatory increase in expression or activity of the homologous hormone by the placenta; and genetic linkage between the two effects. Gestational drive may therefore be a common selection pressure experienced by any of the various hormones of mammalian pregnancy that have arisen by tandem gene duplication. We examine the evolution of chorionic gonadotropin in the human lineage in light of this hypothesis. Finally, we postulate that some of the difficulties of human pregnancy may be a consequence of the action of selfish genes.
PubMed: 36050940
DOI: 10.1093/emph/eoac031 -
Environment International Aug 2023Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have...
BACKGROUND
Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated.
OBJECTIVES
To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations.
METHODS
We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture.
RESULTS
In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: -0.06 [-0.11 to -0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: -0.13 [-0.19 to -0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with -0.27 lower hCG (95% CI: -0.34 to -0.19).
DISCUSSION
Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.
Topics: Pregnancy; Child; Humans; Female; Endocrine Disruptors; Diethylhexyl Phthalate; Polychlorinated Biphenyls; Longitudinal Studies; Phthalic Acids; Chorionic Gonadotropin; Environmental Pollutants; Environmental Exposure
PubMed: 37459690
DOI: 10.1016/j.envint.2023.108091