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Veterinary Pathology Nov 2016The decidua is the superficial portion of endometrium that transforms, or decidualizes, under the influence of progesterone to nourish the early embryo during pregnancy....
The decidua is the superficial portion of endometrium that transforms, or decidualizes, under the influence of progesterone to nourish the early embryo during pregnancy. Deciduae outside the uterus are found in nearly 100% of human pregnancies. This condition, known as deciduosis, may mimic malignancy, resulting in additional diagnostic procedures that place the mother, baby, or both at risk. Deciduosis has been described in both Old World and New World nonhuman primates in conjunction with pregnancy and after treatment with exogenous progestins. Here the authors present 6 cases of deciduosis associated with endometriotic lesions in female rhesus and cynomolgus macaques (Macaca mulatta and Macaca fascicularis). Full diagnostic necropsies with histologic analyses were performed on all animals. Deciduae were stained with hematoxylin and eosin and by immunohistochemistry for vimentin, CD10, progesterone receptor, estrogen receptor, desmin, cytokeratin, kermix P8, chorionic gonadotropin, human placental lactogen, and calretinin. The most common clinical signs were abdominal pain (4 of 6) and anorexia (2 of 6). At necropsy, macaque uteri were often enlarged or disfigured (4 of 6) with abundant fibrous adhesions (5 of 6). Affected tissue consisted of epithelial-lined cysts and decidualized stroma with scattered gamma/delta T cells. Decidualized stromal cells were large and polyhedral with abundant cytoplasm and round vesicular nuclei. They stained positive for vimentin, CD10, progesterone, and estrogen. In summary, these cases illustrate deciduosis in 6 nonhuman primates with endometriosis. Understanding decidualization in nonhuman primates will aid in elucidating the pathophysiology of deciduosis during pregnancy or endometriosis and potentially lead to new interventions.
Topics: Animals; Decidua; Endometriosis; Endometrium; Female; Macaca fascicularis; Macaca mulatta; Monkey Diseases
PubMed: 27281017
DOI: 10.1177/0300985816646433 -
Uterine glands: biological roles in conceptus implantation, uterine receptivity and decidualization.The International Journal of... 2014All mammalian uteri contain glands in the endometrium that synthesize or transport and secrete substances essential for survival and development of the conceptus... (Review)
Review
All mammalian uteri contain glands in the endometrium that synthesize or transport and secrete substances essential for survival and development of the conceptus (embryo/fetus and associated extraembryonic membranes). This review summarizes information related to the biological roles of uterine glands and their secretions in uterine receptivity, blastocyst/conceptus survival and implantation, and stromal cell decidualization. Studies with the ovine uterine gland knockout (UGKO) model support a primary role for uterine glands and, by inference, their secretions present in uterine luminal fluid histrotroph for conceptus survival and development. In rodents, studies with mutant and progesterone-induced UGKO mice found that uterine glands and their secretions are unequivocally required for establishment of uterine receptivity and blastocyst implantation and also may influence blastocyst trophectoderm activation and stromal cell decidualization in the uterus. Similarly in humans, histotroph from uterine glands appears critical for blastocyst implantation, uterine receptivity, and conceptus nutrition during the first trimester and uterine glands likely have a role in stromal cell decidualization. An increased understanding of uterine gland biology is important for diagnosis, prevention and treatment of fertility problems, particularly infertility and recurrent pregnancy loss, in domestic animals and humans.
Topics: Animals; Decidua; Embryo Implantation; Embryo, Mammalian; Female; Humans; Uterus
PubMed: 25023676
DOI: 10.1387/ijdb.130344ts -
Biomolecules May 2021Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising... (Review)
Review
Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure-derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.
Topics: Animals; Cell Proliferation; Decidua; Female; HMGA1a Protein; Humans; Pre-Eclampsia; Pregnancy; Trophoblasts
PubMed: 34072941
DOI: 10.3390/biom11060822 -
Cellular and Molecular Life Sciences :... Jun 2020Decidualization is a critical event for the blastocyst implantation, placental development and fetal growth and the normal term. In mice, the embryo implantation to the... (Review)
Review
Decidualization is a critical event for the blastocyst implantation, placental development and fetal growth and the normal term. In mice, the embryo implantation to the uterine epithelial would trigger the endometrial stromal cells to differentiate into decidual stromal cells. However, decidualization in women takes place from the secretory phase of each menstrual cycle and continues to early pregnancy if there is conceptus. Deficient decidualization is often associated with pregnancy specific complications and reproductive disorders. Dramatic changes occur in the gene expression profiles during decidualization, which is coordinately regulated by steroid hormones, growth factors, and molecular and epigenetic mechanisms. Recently, emerging evidences showed that epigenetic modifications, mainly including DNA methylation, histone modification, and non-coding RNAs, play an important role in the decidualization process via affecting the target genes' expression. In this review, we will focus on the epigenetic modifications in decidualization and open novel avenues to predict and treat the pregnancy complications caused by abnormal decidualization.
Topics: Animals; DNA Methylation; Decidua; Endometrium; Epigenesis, Genetic; Female; Histone Code; Humans; Pregnancy; Stromal Cells
PubMed: 31813015
DOI: 10.1007/s00018-019-03395-9 -
Human Reproduction (Oxford, England) Oct 2019What is the stiffness (elastic modulus) of human nonpregnant secretory phase endometrium, first trimester decidua, and placenta? (Observational Study)
Observational Study
STUDY QUESTION
What is the stiffness (elastic modulus) of human nonpregnant secretory phase endometrium, first trimester decidua, and placenta?
SUMMARY ANSWER
The stiffness of decidua basalis, the site of placental invasion, was an order of magnitude higher at 103 Pa compared to 102 Pa for decidua parietalis, nonpregnant endometrium and placenta.
WHAT IS KNOWN ALREADY
Mechanical forces have profound effects on cell behavior, regulating both cell differentiation and migration. Despite their importance, very little is known about their effects on blastocyst implantation and trophoblast migration during placental development because of the lack of mechanical characterization at the human maternal-fetal interface.
STUDY DESIGN, SIZE, DURATION
An observational study was conducted to measure the stiffness of ex vivo samples of human nonpregnant secretory endometrium (N = 5) and first trimester decidua basalis (N = 6), decidua parietalis (N = 5), and placenta (N = 5). The stiffness of the artificial extracellular matrix (ECM), Matrigel®, commonly used to study migration of extravillous trophoblast (EVT) in three dimensions and to culture endometrial and placental organoids, was also determined (N = 5).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Atomic force microscopy was used to perform ex vivo direct measurements to determine the stiffness of fresh tissue samples. Decidua was stained by immunohistochemistry (IHC) for HLA-G+ EVT to confirm whether samples were decidua basalis or decidua parietalis. Endometrium was stained with hematoxylin and eosin to confirm the presence of luminal epithelium. Single-cell RNA sequencing data were analyzed to determine expression of ECM transcripts by decidual and placental cells. Fibrillin 1, a protein identified by these data, was stained by IHC in decidua basalis.
MAIN RESULTS AND THE ROLE OF CHANCE
We observed that decidua basalis was significantly stiffer than decidua parietalis, at 1250 and 171 Pa, respectively (P < 0.05). The stiffness of decidua parietalis was similar to nonpregnant endometrium and placental tissue (250 and 232 Pa, respectively). These findings suggest that it is the presence of invading EVT that is driving the increase in stiffness in decidua basalis. The stiffness of Matrigel® was found to be 331 Pa, significantly lower than decidua basalis (P < 0.05).
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
Tissue stiffness was derived by ex vivo measurements on blocks of fresh tissue in the absence of blood flow. The nonpregnant endometrium samples were obtained from women undergoing treatment for infertility. These may not reflect the stiffness of endometrium from normal fertile women.
WIDER IMPLICATIONS OF THE FINDINGS
These results provide direct measurements of tissue stiffness during the window of implantation and first trimester of human pregnancy. They serve as a basis of future studies exploring the impact of mechanics on embryo implantation and development of the placenta. The findings provide important baseline data to inform matrix stiffness requirements when developing in vitro models of trophoblast stem cell development and migration that more closely resemble the decidua in vivo.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Centre for Trophoblast Research, the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z), the Medical Research Council (MR/P001092/1), the European Research Council (772426), an Engineering and Physical Sciences Research Council Doctoral Training Award (1354760), a UK Medical Research Council and Sackler Foundation Doctoral Training Grant (RG70550) and a Wellcome Trust Doctoral Studentship (215226/Z/19/Z).
Topics: Blastocyst; Cell Movement; Collagen; Decidua; Drug Combinations; Elastic Modulus; Elasticity Imaging Techniques; Embryo Implantation; Endometrium; Extracellular Matrix; Female; Humans; Laminin; Microscopy, Atomic Force; Placenta; Placentation; Pregnancy; Pregnancy Trimester, First; Proteoglycans
PubMed: 31579915
DOI: 10.1093/humrep/dez139 -
Advances in Anatomy, Embryology, and... 2015Implantation and the establishment of pregnancy are critical for the propagation of the species, but yet remain the limiting steps in human and primate reproduction.... (Review)
Review
Implantation and the establishment of pregnancy are critical for the propagation of the species, but yet remain the limiting steps in human and primate reproduction. Successful implantation requires a competent blastocyst and a receptive endometrium during a specific window of time during the menstrual cycle to initiate the bilateral communication required for the establishment of a successful pregnancy. This chapter provides an overview of these processes and discusses the molecular mechanisms associated with implantation of the blastocyst and decidualization of the uterus in primates.
Topics: Animals; Decidua; Embryo Implantation; Endometrium; Female; Humans; Pregnancy; Primates
PubMed: 26450500
DOI: 10.1007/978-3-319-15856-3_10 -
Proceedings of the National Academy of... Aug 2022The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent...
The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent studies have implicated dysregulated expression of the interleukin-1 (IL-1) family cytokine, IL-33, and its receptor, ST2, in poor pregnancy outcomes in women, including recurrent pregnancy loss, preeclampsia, and preterm labor. How IL-33 supports pregnancy progression in vivo is not well understood. Here, we demonstrate that maternal IL-33 signaling critically regulates uterine tissue remodeling and immune cell function during early pregnancy in mice. IL-33-deficient dams exhibit defects in implantation chamber formation and decidualization, and abnormal vascular remodeling during early pregnancy. These defects coincide with delays in early embryogenesis, increased resorptions, and impaired fetal and placental growth by late pregnancy. At a cellular level, myometrial fibroblasts, and decidual endothelial and stromal cells, are the main IL-33 cell types in the uterus during decidualization and early placentation, whereas ST2 is expressed by uterine immune populations associated with type 2 immune responses, including ILC2s, Tregs, CD4 T cells, M2- and cDC2-like myeloid cells, and mast cells. Early pregnancy defects in IL-33-deficient dams are associated with impaired type 2 cytokine responses by uterine lymphocytes and fewer Arginase-1 macrophages in the uterine microenvironment. Collectively, our data highlight a regulatory network, involving crosstalk between IL-33-producing nonimmune cells and ST2 immune cells at the maternal-fetal interface, that critically supports pregnancy progression in mice. This work has the potential to advance our understanding of how IL-33 signaling may support optimal pregnancy outcomes in women.
Topics: Animals; Decidua; Female; Fetus; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Lymphocytes; Mice; Placenta; Placentation; Pregnancy; Uterus
PubMed: 35994660
DOI: 10.1073/pnas.2123267119 -
Journal of Assisted Reproduction and... May 2016
Review
Topics: Abortion, Habitual; Adult; Blastocyst; Chromosome Aberrations; Decidua; Embryo Implantation; Female; Fertility; Humans; Karyotype
PubMed: 26843392
DOI: 10.1007/s10815-016-0658-8 -
Placenta Aug 2020Preeclampsia is the archetype of a spectrum of clinical disorders related to abnormal placental development or function, characterized by placental histological lesions.... (Review)
Review
Preeclampsia is the archetype of a spectrum of clinical disorders related to abnormal placental development or function, characterized by placental histological lesions. Among those lesions, decidual vasculopathy is a term used to describe lesions of maternal spiral arteries, which are encountered on placental examination in about half of the women with preeclampsia. The morphological features of the lesions include perivascular lymphocytic infiltration, fibrinoid necrosis and foam cell incorporation within the vessel wall. Due to the resemblance of the latter characteristic to atherosclerosis, they are alternatively termed acute atherosis. Decidual vasculopathy correlates with worse maternal and neonatal outcomes, as well as placental pathology. In this article, we review the available literature on decidual vasculopathy and address the pitfalls in histological analysis of the lesions, including the varying definitions of the lesions and sample collection methods. We also discuss the current evidence on the etiology of the lesions and propose a novel hypothesis linking the three etiological pathways to the formation of decidual vasculopathy and, ultimately, the emergence of the heterogeneous group of placental dysfunction disorders, known as the great obstetric syndromes.
Topics: Arteries; Decidua; Female; Humans; Pre-Eclampsia; Pregnancy; Vascular Diseases; Vascular Remodeling
PubMed: 32792071
DOI: 10.1016/j.placenta.2020.06.020 -
Placenta Dec 2017In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal... (Review)
Review
In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier. Therefore, in this review, we focus on the emerging prospective evidence supporting the concept that deficient or defective endometrial maturation in the late secretory phase and during early pregnancy, i.e., pre-decidualization and decidualization, respectively, may contribute to the genesis of preeclampsia. The first prospectively-acquired data directly supporting this concept were unexpectedly revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained during the first trimester of women who developed preeclampsia 5 months later. Additional supportive evidence arose from investigations of Natural Killer cells in first trimester decidua from elective terminations of women with high resistance uterine artery indices, a surrogate for deficient trophoblast invasion. Last, circulating insulin growth factor binding protein-1, which is secreted by decidual stromal cells was decreased during early pregnancy in women who developed preeclampsia. We conclude this review by making recommendations for further prospectively-designed studies to corroborate the concept of endometrial antecedents of preeclampsia. These studies could also enable identification of women at increased risk for developing preeclampsia, unveil the molecular mechanisms of deficient or defective (pre)decidualization, and lead to preventative strategies designed to improve (pre)decidualization, thereby reducing risk for preeclampsia development.
Topics: Decidua; Female; Gene Expression; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 28693893
DOI: 10.1016/j.placenta.2017.06.005