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Exosomes pregnancy

Dionne Tannetta, Gavin Collett, Manu Vatish, Chris Redman, Ian Sargent
The ability to directly monitor the status of the placenta throughout pregnancy would be a major advance in both general and personalized obstetric care, allowing treatments to be tailored to the dynamic changes that can occur in gestation. Syncytiotrophoblast extracellular vesicles (STBEV) are membrane bound vesicles, released from the surface of the placenta directly into the maternal circulation, in the form of exosomes, microvesicles and apoptotic bodies. They carry many syncytiotrophoblast derived factors such as proteins, lipids, glycans and nucleic acids, which together could dynamically signal to the mother the status of the placenta...
November 16, 2016: Placenta
Samantha Sheller-Miller, Jun Lei, George Saade, Carlos Salomon, Irina Burd, Ramkumar Menon
Timing and initiation of labor are well-orchestrated by signals communicated between the fetal and maternal compartments; however, how these signals are communicated is not completely understood. Fetal exosomes, intercellular signaling vesicles, may play a key role in the process. The objective of this study was to evaluate exosome trafficking in vivo from fetal to maternal compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational day 16 and 17 with exosomes isolated from primary human amnion epithelial cells fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)...
2016: Frontiers in Pharmacology
Yong Qin Koh, Hassendrini N Peiris, Kanchan Vaswani, Sarah Reed, Gregory E Rice, Carlos Salomon, Murray D Mitchell
BACKGROUND: Cell-to-cell communication between the blastocyst and endometrium is critical for implantation. In recent years, evidence has emerged from studies in humans and several other animal species that exosomes are secreted from the endometrium and trophoblast cells and may play an important role in cell-to-cell communication maternal-fetal interface during early pregnancy. Exosomes are stable extracellular lipid bilayer vesicles that encapsulate proteins, miRNAs, and mRNAs, with the ability to deliver their cargo to near and distant sites, altering cellular function(s)...
November 9, 2016: Reproductive Biology and Endocrinology: RB&E
Kristin M Klohonatz, Ashley D Cameron, Joanna R Hergenreder, Juliano C da Silveira, Aeriel D Belk, D N R Veeramachaneni, Gerrit J Bouma, Jason E Bruemmer
During early pregnancy the conceptus and mare communicate to establish pregnancy. Cell-secreted vesicles (e.g. exosomes) have been reported in serum. Exosomes contain bioactive materials, such as miRNA, that can mediate cell responses. We hypothesized that (i) exosomes are present in mare circulation and quantity varies with pregnancy status, (ii) exosomes contain miRNAs unique to pregnancy status, and (iii) miRNAs target pathways in endometrium based upon pregnancy status of the mare. First, serum samples were obtained from mares in a crossover design, with each mare providing samples from a pregnant and non-mated control cycle (n = 3/sample day) on Days 12, 14, 16, and 18 post-ovulation...
October 19, 2016: Biology of Reproduction
Preenan Pillay, Niren Maharaj, Jagidesa Moodley, Irene Mackraj
INTRODUCTION AND AIM: Exosomes are a subtype of extracellular vesicle (20-130 nm) released by biological cells under normal and pathological conditions. Although there have been reports of circulating exosomes in normal pregnancy, the relevance of placental-derived exosomes in normal and abnormal pregnancies still needs to be elucidated. The aim of this study was to quantify total and placental-derived exosomes in maternal plasma from normal (N), early onset- and late onset-preeclampsia (PE)...
October 2016: Placenta
Dionne Tannetta, Ieva Masliukaite, Manu Vatish, Christopher Redman, Ian Sargent
The release of extracellular vesicles (EV) by the syncytiotrophoblast (STB) may be an important mechanism by which the placenta signals to the mother. STB derived EV (STBEV) are comprised predominantly of exosomes (50-150nm) and microvesicles (100-1000nm) that contain bioactive mediators such as proteins, nucleic acids and lipids. They, along with larger syncytial nuclear aggregates are released by the STB into the maternal circulation throughout gestation in normal pregnancy where they appear to have an immunoregulatory role, inhibiting T cell and NK cell responses...
August 24, 2016: Journal of Reproductive Immunology
R Linsingen, M G Bicalho, N S Carvalho
Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, immunological factors also appear to be involved. Recently, molecular genetic studies have helped us better understand the underlying pathophysiologic processes...
July 5, 2016: Journal of Maternal-fetal & Neonatal Medicine
M D Mitchell, K Scholz-Romero, S Reed, H N Peiris, Y Q Koh, S Meier, C G Walker, C R Burke, J R Roche, G Rice, C Salomon
Cell-to-cell communication in physiological and pathological conditions may be influenced by neighboring cells, distant tissues, or local environmental factors. Exosomes are specific subsets of extracellular vesicles that internalize and deliver their content to near and distant sites. Exosomes may play a role in the maternal-embryo crosstalk vital for the recognition and maintenance of a pregnancy; however, their role in dairy cow reproduction has not been established. This study aimed to characterize the exosome profile in the plasma of 2 strains of dairy cow with divergent fertility phenotypes...
September 2016: Journal of Dairy Science
Keigo Nakamura, Kazuya Kusama, Rulan Bai, Toshihiro Sakurai, Kazuto Isuzugawa, James D Godkin, Yoshihito Suda, Kazuhiko Imakawa
Biochemical and/or physical communication between the conceptus and the uterine endometrium is required for conceptus implantation to the maternal endometrium, leading to placentation and the establishment of pregnancy. We previously reported that in vitro co-culture system with bovine trophoblast CT-1 cells, primary uterine endometrial epithelial cells (EECs), and uterine flushings (UFs) mimics in vivo conceptus attachment process. To identify molecules in UFs responsible for this change, we first characterized protein contents of UFs from day 17 cyclic (C17) and pregnant (P17) ewes through the use of two dimensional-Polyacrylamide Gel Electrophoresis (2D-PAGE), followed by Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) analysis...
2016: PloS One
Eduardo S Ribeiro, José E P Santos, William W Thatcher
Elongation of the preimplantation conceptus is a prerequisite for successful pregnancy in ruminants and depends on histotroph secretion by the endometrium. Lipids are an essential component of the histotroph, and recent studies indicate that lipids have important roles in the elongation phase of conceptus development. The onset of elongation is marked by dynamic changes in the transcriptome of trophectoderm cells, which are associated with lipid metabolism. During elongation, the trophectoderm increases transcript expression of genes related to uptake, metabolism and de novo biosynthesis of fatty acids and prostaglandins...
October 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Samantha Sheller, John Papaconstantinou, Rheanna Urrabaz-Garza, Lauren Richardson, George Saade, Carlos Salomon, Ramkumar Menon
At term, the signals of fetal maturity and feto-placental tissue aging prompt uterine readiness for delivery by transitioning quiescent myometrium to an active stage. It is still unclear how the signals reach the distant myometrium. Exosomes are a specific type of extracellular vesicle (EVs) that transport molecular signals between cells, and are released from a wide range of cells, including the maternal and fetal cells. In this study, we hypothesize that i) exosomes act as carriers of signals in utero-placental compartments and ii) exosomes reflect the physiologic status of the origin cells...
2016: PloS One
J G Nicoletti, B G White, E I Miskiewicz, D J MacPhee
During pregnancy the myometrium undergoes a programme of differentiation induced by endocrine, cellular, and biophysical inputs. Small heat shock proteins (HSPs) are a family of ten (B1-B10) small-molecular-weight proteins that not only act as chaperones, but also assist in processes such as cytoskeleton rearrangements and immune system activation. Thus, it was hypothesized that HSPB5 (CRYAB) would be highly expressed in the rat myometrium during the contractile and labour phases of myometrial differentiation when such processes are prominent...
July 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
C Albrecht, I Caniggia, V Clifton, C Göhner, L Harris, D Hemmings, A Jawerbaum, E Johnstone, H Jones, J Keelan, R Lewis, M Mitchell, P Murthi, T Powell, R Saffery, R Smith, C Vaillancourt, C Wadsack, C Salomon
Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology; 2) xenobiotics and endocrine disruptors and pregnancy; 3) lipid mediators and placental function...
January 6, 2016: Placenta
Wenyi Qin, Yoshikazu Tsukasaki, Santanu Dasgupta, Nitai Mukhopadhyay, Mitsuo Ikebe, Edward R Sauter
PURPOSE: Pregnancy increases breast cancer risk for all women for at least 5 years after parturition. During weaning and involution, the breast microenvironment becomes tumor promotional. Exosomes provide cell-cell communication during physiologic processes such as lactation, but also in breast cancer. We determined whether molecules in milk exosomes from healthy lactating women modulate the development and progression of breast cancer. EXPERIMENTAL DESIGN: Thirteen nursing women provided three (transitional, mature, and wean) milk samples...
September 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Carlos A Escudero, Kurt Herlitz, Felipe Troncoso, Jesenia Acurio, Claudio Aguayo, James M Roberts, Grace Truong, Gregory Duncombe, Gregory Rice, Carlos Salomon
Preeclampsia is a syndrome characterized by hypertension during pregnancy, which is a leading cause of morbidity and mortality in both mother and newborn in developing countries. Some advances have increased the understanding of pathophysiology of this disease. For example, reduced utero-placental blood flow associated with impaired trophoblast invasion may lead to a hypoxic placenta that releases harmful materials into the maternal and feto-placental circulation and impairs endothelial function. Identification of these harmful materials is one of the hot topics in the literature, since these provide potential biomarkers...
2016: Frontiers in Physiology
Stefan M Gysler, Melissa J Mulla, Marta Guerra, Jan J Brosens, Jane E Salmon, Lawrence W Chamley, Vikki M Abrahams
STUDY QUESTION: What is the role of microRNAs (miRs) in antiphospholipid antibody (aPL)-induced trophoblast inflammation? SUMMARY ANSWER: aPL-induced up-regulation of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR-146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the RNA sensor, TLR8. WHAT IS KNOWN ALREADY: Obstetric antiphospholipid syndrome (APS) is an autoimmune disorder characterized by circulating aPL and an increased risk of pregnancy complications...
July 2016: Molecular Human Reproduction
John V Ilekis, Ekaterini Tsilou, Susan Fisher, Vikki M Abrahams, Michael J Soares, James C Cross, Stacy Zamudio, Nicholas P Illsley, Leslie Myatt, Christine Colvis, Maged M Costantine, David M Haas, Yoel Sadovsky, Carl Weiner, Erik Rytting, Gene Bidwell
Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap...
July 2016: American Journal of Obstetrics and Gynecology
Gregory W Burns, Kelsey E Brooks, Thomas E Spencer
Cells release diverse types of membrane-bound vesicles of endosomal and plasma membrane origin, termed exosomes and microvesicles, respectively. Extracellular vesicles (EVs) represent an important mode of intercellular communication by transferring select RNAs, proteins, and lipids between cells. The present studies tested the hypothesis that the elongating ovine conceptus and uterus produces EVs that mediate conceptus-maternal interactions during early pregnancy. In Study 1, EVs were purified from uterine luminal fluid of Day 14 cyclic sheep...
March 2016: Biology of Reproduction
David W Greening, Hong P T Nguyen, Kirstin Elgass, Richard J Simpson, Lois A Salamonsen
Embryo implantation into receptive endometrium requires synergistic endometrial-blastocyst interactions within the uterine cavity and is essential for establishing pregnancy. We demonstrate that exosomes (40-150 nm nanovesicles) released from endometrial epithelial cells are an important component of these interactions. We defined the proteome of purified endometrial epithelial-derived exosomes (Exos) influenced by menstrual cycle hormones estrogen (E; proliferative phase) and estrogen plus progesterone (EP; receptive phase) and examined their potential to modify trophoblast function...
February 2016: Biology of Reproduction
Lindsey A Burnett, Romana A Nowak
Shedding of exosomes and microvesicles is now a well-recognized, important method of cell-cell communication in a number of different cell types. However, their importance in the female reproductive tract and in mediating embryo-maternal interactions during pregnancy has only recently been recognized. Here we review the current literature as to release of extracellular vesicles by uterine cells, the embryo,, and placental trophoblast cells; how release is regulated; and the different types of signaling molecules and genetic information contained within such vesicles...
2016: Frontiers in Bioscience (Scholar Edition)
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