532. SOLUBLE MEDIATORS IN THE HUMAN UTERINE CAVITY: POTENTIAL ROLES IN EMBRYO IMPLANTATION

2009 ◽  
Vol 21 (9) ◽  
pp. 130
Author(s):  
N. Hannan ◽  
K. L. Meehan ◽  
L. J. F. Rombauts ◽  
L. A. Salamonsen
Keyword(s):  
Chemokine Receptors ◽  
Embryo Implantation ◽  
Uterine Cavity ◽  
Cycle Phase ◽  
Human Trophoblast ◽  
Endometrial Epithelial Cell ◽  
Glandular Secretion ◽  
Uterine Fluid ◽  
Human Chemokines ◽  
Insight Into

Embryo implantation requires synchronized dialogue between a receptive endometrium and an activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle there is increased glandular secretion into the uterine lumen. These secretions likely contain important mediators that modulate the endometrium and support the conceptus during implantation. Previously we identified that several chemokines were maximally produced during the MS phase by endometrial glandular epithelium (GE) (1, 2) and the presence of chemokine receptors on GE and human trophoblast (3). Furthermore recombinant human chemokines and endometrial epithelial cell-conditioned media stimulated trophoblast migration; this was attenuated by neutralizing specific chemokines (3). Chemokines also regulate a variety of adhesion and ECM molecules on trophoblast (4). Thus chemokines have important roles during embryo implantation. We hypothesized that chemokines are secreted into the uterine cavity and may act on the implanting blastocyst and the endometrium. This study aimed to identify chemokines in uterine fluid (collected by flushing the uterine cavity with 5mls of saline) from fertile women during the proliferative (non-receptive; n=4) and MS (receptive; n=4) phases of the cycle, and from women with unexplained infertility during the MS phase (n=4). Uterine fluid was analyzed using quantitative MilliplexTM Luminex® 42-plex cytokine/chemokine assays revealing the presence of IL-8, CCL2, CCL4, CCL7, CCL11, CCL22 and CX3CL1 in uterine fluid from all women. Importantly chemokine profiles were altered with both cycle phase and fertility; for example CCL4 and CCL22 levels were lower in the infertile cohort, where as CCL2 levels were higher in uterine fluid collected during the proliferative phase. Identifying the soluble mediators in human uterine fluid may provide potential markers of endometrial receptivity, insight into the unique microenvironment essential for pregnancy and a profile of maternal factors that influence the implanting blastocyst.

155. UNDERSTANDING THE CROSSTALK IN THE HUMAN UTERINE CAVITY: ROLES FOR SOLUBLE MEDIATORS DURING EMBRYO IMPLANTATION

2010 ◽  
Vol 22 (9) ◽  
pp. 73
Author(s):  
N. Hannan ◽  
P. Paiva ◽  
K. L. Meehan ◽  
C. Hincks ◽  
L. J. F. Rombauts ◽  
...  
Keyword(s):  
Menstrual Cycle ◽  
Embryo Implantation ◽  
Uterine Cavity ◽  
Uterine Receptivity ◽  
Adhesive Properties ◽  
Infertile Women ◽  
Functional Studies ◽  
Glandular Secretion ◽  
Uterine Fluid ◽  
Insight Into

Embryo implantation requires synchronized dialogue between a receptive endometrium and an activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle there is increased glandular secretion into the uterine lumen. These secretions contain important mediators that modulate the endometrium and support the conceptus during implantation. Analysis of the composition of uterine fluid across the menstrual cycle and in fertile and infertile women will, therefore, provide new insights into uterine receptivity. We hypothesized that multiplex platform analysis of human uterine lavages would identify soluble mediators important for the establishment of pregnancy in humans. Lavages were collected (by flushing the uterine cavity with 5mL of saline) from fertile and infertile women during the MS phase and from fertile women during the mid-proliferative (MP) phase of the menstrual cycle. Comparison of lavages from the three cohorts was performed using quantitative MilliplexTM Luminex® cytokine/chemokine assays containing 42-analytes. Luminex analysis detected a number of cytokines in uterine fluid, revealing 8 soluble mediators previously unknown in the endometrium and present in human uterine fluid including, PDGF-AA, TNFβ, sIL-2Rα, Flt-3 ligand, sCD40L, IL-7, IFNα2 and GRO. Furthermore comparison of the three cohorts revealed VEGF levels were significantly higher in the fertile (MS) fluid when compared to infertile. Functional studies demonstrated that rhVEGF treatment significantly increased the adhesive properties in cells present at the maternal-fetal interface. These findings suggest VEGF plays a role in regulating embryo implantation. Furthermore identifying the soluble mediators in uterine fluid may provide potential markers of endometrial receptivity, insight into the unique microenvironment essential for pregnancy and a profile of maternal factors that influence the implanting blastocyst.

216. Activin A regulates trophoblast cell adhesion: implications for uterine receptivity and embryo implantation

2008 ◽  
Vol 20 (9) ◽  
pp. 16
Author(s):  
C. J. Stoikos ◽  
A. O.'Connor ◽  
L. A. Salamonsen ◽  
E. Dimitriadis
Keyword(s):  
Embryo Implantation ◽  
Uterine Cavity ◽  
Activin A ◽  
Trophoblast Cell ◽  
Collagen I ◽  
Trophoblast Invasion ◽  
Uterine Receptivity ◽  
Adhesive Properties ◽  
Secretory Phase ◽  
Human Trophoblast

Embryo implantation involves blastocyst attachment to the endometrial luminal epithelium, followed by trophoblast invasion. This process involves a coordinated crosstalk between the implanting blastocyst and the endometrium. Adhesion molecules play an instrumental role during implantation and are regulated by a variety of factors including cytokines and growth factors. Activin A, a TGF-β superfamily member, has been detected in uterine washings,1 and its subunit, β A, is produced by endometrial glands during the secretory phase of the menstrual cycle.2 In endometriosis, a disease that associated with sub-fertility, β A immunostaining is increased in endometrial glands,3 suggesting higher levels of activin A secreted into the uterine lumen could contribute to sub-fertility observed in endometriosis. Therefore we hypothesised that activin A secretion into the uterine cavity affects the adhesive properties of the cells present at the maternal-fetal interface. The aims of the study were to measure and compare activin A secretion in uterine washings from women with and without endometriosis and to demonstrate whether activin A regulates adhesion to extracellular matrix (ECM) components. Uterine washings (5 mL of sterile saline) were collected from women with and without endometriosis during the secretory phase. Activin A was measured by ELISA. HTR8 (human trophoblast cell-line) cells were treated with rhActivin A (50 ng/mL) and assessed for binding to fibronectin, laminin, vitronectin, collagen I and IV. Activin A (>10pg/mL) was detectable in uterine washings from women with and without endometriosis and levels were elevated in endometriosis patients. Untreated HTR8 cells adhered maximally to fibronectin, collagen I and collagen IV with low binding to vitronectin and laminin. Following activin treatment, HTR8 cell binding to fibronectin, collagen I and IV was significantly decreased (n = 3, P < 0.05). These results suggest that activin A regulates the adhesive properties of the blastocyst during implantation. This study also implies that abnormalities in local activin A levels during endometrial receptivity may contribute to sub-fertility in women. (1) Petraglia et., al. (1998) J Clin Endocrinol Metab. (2) Jones et., al. (2000) Mol Hum Reprod. (3) Rombauts et., al. (2006) Aust N Z J Obstet Gynaecol.

scholarly journals Uterine secretome and its modulation in rat (Rattus norvegicus)

Reproduction ◽  
2013 ◽  
Vol 146 (1) ◽  
pp. 13-26 ◽  
Author(s):  
Sumit Bhutada ◽  
R R Katkam ◽  
Tarla Nandedkar ◽  
S M Metkari ◽  
U K Chaudhari ◽  
...  
Keyword(s):  
Protein Profile ◽  
Embryo Implantation ◽  
Pregnant Rats ◽  
Differential Abundance ◽  
Endometrial Epithelial Cell ◽  
Epithelial Cell Lines ◽  
Guanine Nucleotide Dissociation Inhibitor ◽  
Uterine Fluid ◽  
Liquid Chromatography Tandem Mass ◽  
Culture Supernatants

The present study identifies uterine fluid (UF) proteins that display differential abundance during the embryo-permissive phase in nonconception and conception cycles in rats. UF samples were collected from nonpregnant rats in the proestrous (n=17) and metestrous (n=18) phases and also from pregnant (n=17) and pseudopregnant (n=17) rats on day 4 post coitus. UF protein profile in the metestrous phase was compared with that in the proestrous phase. Similarly, UF protein profile of the pregnant rats was compared with that of the pseudopregnant rats. Two-dimensional PAGE, followed by densitometric analysis of the paired protein spots, revealed differential abundance of 44 proteins in the metestrous phase, compared with that in the proestrous phase. Of these, 29 proteins were identified by matrix-assisted laser desorption/ionization time-of-flight or liquid chromatography–tandem mass spectrometry. Functional groups such as proteases, protease inhibitors, and oxidoreductases were enriched in differentially abundant proteins. Total protease activity in UF was found to be significantly (P<0.05; t-test) higher in the proestrous phase, compared with that in the metestrous phase. Furthermore, 41 UF proteins were found to be differentially abundant in pregnant rats, compared with pseudopregnant rats. Of these, 11 proteins could be identified. Immunoblotting analysis confirmed significantly higher (P<0.05; t-test) abundance of β-actin, Rho-specific guanine nucleotide dissociation inhibitor alpha (Rho-GDIα), and peroxiredoxin-2 and -6 in the metestrous phase, compared with that in the proestrous phase. Compared with pseudopregnant rats, pregnant rats had significantly higher (P<0.05; t-test) levels of UF β-actin and Rho-GDIα. Furthermore, these proteins could be detected in the culture supernatants of endometrial epithelial cell lines, thereby providing an evidence of their secretion from endometrial epithelial cells. Data obtained from the study expand our knowledge on the uterine milieu that favours embryo implantation.

NLRP3 Promotes Endometrial Receptivity by Inducing Epithelial-Mesenchymal Transition of the Endometrial Epithelium

2021 ◽  
Author(s):  
Xi Cheng ◽  
Yu Zhang ◽  
Jinzhao Ma ◽  
Shuxian Wang ◽  
Rujun Ma ◽  
...  
Keyword(s):  
Immune Responses ◽  
Epithelial Mesenchymal Transition ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Mesenchymal Transition ◽  
Endometrial Epithelial Cell ◽  
Endometrial Epithelium ◽  
Insight Into ◽  
Recognition Receptor ◽  
Endometrial Epithelial Cells

Abstract Endometrial receptivity is crucial for successful embryo implantation It is regulated by multiple factors which include ovarian steroid hormones and the immune microenvironment among others. Nod Like Receptor Pyrins-3 (NLRP3) is a key intracellular pattern-recognition receptor and a critical component of the inflammasome, which plays an essential role in the development of inflammation and of immune responses. However, the physiological functions of NLRP3 in the endometrium remain largely unclear. This study investigated the physiological and pathological significance of NLRP3 in human endometrial epithelial cell during the implantation window. NLRP3 is highly expressed during the mid-proliferative and mid-secretory phases of the human endometrium and transcriptionally up-regulated by estradiol (E2) through estrogen receptor β (ERβ). In addition, NLRP3 promotes embryo implantation and enhances epithelial-mesenchymal transition (EMT) of Ishikawa (IK) cells via both inflammasome-dependent and inflammasome-independent pathways, which might provide a novel insight into endometrial receptivity and embryo implantation. Our findings suggest that NLRP3, which is transcriptionally regulated by E2, induces epithelial-mesenchymal transition of endometrial epithelial cells and promotes embryo adhesion.

The Development of the Embryo and Membranes of the Humpback Whale, Megaptera nodosa (Bonnaterre)

1960 ◽  
Vol 11 (3) ◽  
pp. 365 ◽  
Author(s):  
CW Stump ◽  
JP Robins ◽  
ML Garde
Keyword(s):  
Umbilical Cord ◽  
Uterine Cavity ◽  
Distal Region ◽  
Yolk Sac ◽  
Consecutive Series ◽  
Chorionic Villi ◽  
Suspensory Ligament ◽  
Foetal Membranes ◽  
Uterine Fluid ◽  
Tubular Form

The material consists of 20 embryos (5-30 mm) and two foetuses (63 mm and 90 mm) collected at whaling stations on Moreton and Norfolk Islands (latitude 27� 11'S. and 29� 5' S. respectively) during late August, September, and early October in 1952-53-54 and 1956. The consecutive series permitted the study of membrane formation and organogenesis. Younger embryos are found in grooves between the folds of endometrium in a constant site in that uterine horn associated with the ovary containing the recent corpus luteum. Older embryos and the early foetus are adapted to lie freely in the uterine fluid, and are devoid of any mechanism for apposition or attachment to the endometrium. Variation in the sequence of the association of the components of the umbilical cord provides suspensory structures for the amnion and yolk sac, and for the embryo a bifid ligament, retained in the early foetus for attachment of the foetal membranes. In the younger foetus the allantoic duct drains the nephric secretion into the uterine cavity. In the older foetus chorionic villi are present. The bifid suspensory ligament forms the major part of the distal region of the umbilical cord. The allantoic duct is reunited with the allantoic sac. Amniogenesis is by folding. During the embryonic period the chorio-amniotic connection forms a suspensory ligament. The yolk sac, attached by a novel ligament to the amnion, is large and functional in the embryo. In the foetus vascular splanchnopleure is present in a tubular form. A rete system develops in the embryo.

scholarly journals Donkey genome and insight into the imprinting of fast karyotype evolution

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jinlong Huang ◽  
Yiping Zhao ◽  
Dongyi Bai ◽  
Wunierfu Shiraigol ◽  
Bei Li ◽  
...  
Keyword(s):  
Target Genes ◽  
Karyotype Evolution ◽  
De Novo ◽  
Cycle Phase ◽  
Satellite Sequences ◽  
Chromatid Segregation ◽  
Karyotypic Instability ◽  
Wild Ass ◽  
Genome Assemblies ◽  
Insight Into

Abstract The donkey, like the horse, is a promising model for exploring karyotypic instability. We report the de novo whole-genome assemblies of the donkey and the Asiatic wild ass. Our results reflect the distinct characteristics of donkeys, including more effective energy metabolism and better immunity than horses. The donkey shows a steady demographic trajectory. We detected abundant satellite sequences in some inactive centromere regions but not in neocentromere regions, while ribosomal RNAs frequently emerged in neocentromere regions but not in the obsolete centromere regions. Expanded miRNA families and five newly discovered miRNA target genes involved in meiosis may be associated with fast karyotype evolution. APC/C, controlling sister chromatid segregation, cytokinesis and the establishment of the G1 cell cycle phase were identified by analysis of miRNA targets and rapidly evolving genes.

2-Methoxyoestradiol impairs mouse embryo implantation via F-spondin

2019 ◽  
Vol 31 (4) ◽  
pp. 689
Author(s):  
Emanuel Guajardo-Correa ◽  
Denisse Mena-Silva ◽  
Patricia Diaz ◽  
Carlos Godoy-Guzmán ◽  
Hugo Cardenas ◽  
...  
Keyword(s):  
Mouse Embryo ◽  
Embryo Implantation ◽  
Target Protein ◽  
Methyl Transferase ◽  
Uterine Fluid ◽  
Protein F

The anti-implantation effects of high oestradiol (E2) concentrations could be mediated by E2 metabolites. Herein, we examined whether 2-methoxyoestradiol (2ME) impairs embryo implantation via its target protein F-spondin. Mice on Day 3 of pregnancy were treated with E2 concomitantly with the cathecol-O-methyl transferase inhibitor OR486 and the number of implanted embryos was recorded 5 days later. The effect of 2ME or 4-methoxyoestradiol (4ME) on embryo implantation was also investigated. Plasma and uterine levels of 2ME were measured 0.5, 1 or 3h after E2 treatment while the mRNA for spondin 1 (Spon1) and F-spondin were determined in the uterus 3, 6, 12 or 24h after 2ME treatment. Finally, the effect of a neutralising F-spondin antibody on the anti-implantation effect of 2ME was explored. OR486 blocked the anti-implantation effect of E2; 2ME, but not 4ME, affected embryo implantation. The 2ME concentration was increased after 0.5 and 1h in plasma and 3h in uterine fluid following E2 treatment. 2ME increased levels of Spon1 at 12 and 24h although F-spondin was increased at 12h. F-spondin antibody blocked the effect of 2ME on embryo implantation. We conclude that 2ME impairs mouse embryo implantation via activation of F-spondin in the uterus.

205. Fractalkine, HCC-1 and MIP-1β promote human trophoblast migration

2005 ◽  
Vol 17 (9) ◽  
pp. 78
Author(s):  
N. J. Hannan ◽  
R. L. Jones ◽  
L. A. Salamonsen
Keyword(s):  
Stromal Cells ◽  
Chemokine Receptors ◽  
First Trimester ◽  
Conditioned Media ◽  
Receptor Expression ◽  
Extravillous Trophoblast ◽  
Vitro Assay ◽  
Human Trophoblast ◽  
Decidual Cells ◽  
Trophoblast Migration

Human embryo implantation is a complex process requiring the attachment of an activated blastocyst to receptive endometrial epithelium and subsequent trophoblast invasion throughout the first trimester of pregnancy. Chemokines, including fractalkine (FKN), MCP-3, HCC-1 and MIP-1β, are produced by human endometrial epithelial and decidual cells with maximal production around the time of implantation/early pregnancy.1,2 Chemokine and receptor expression was characterized in cell types at the human maternal–trophoblast interface. Highly abundant expression of chemokine receptors CX3CR1 and CCR1 was observed in first trimester placenta and in trophoblast cells.3 We hypothesized that CX3CR1 and CCR1 ligands (FKN, MCP-3, HCC-1 and MIP-1β) produced by endometrial epithelial and decidualised stromal cells at the time of implantation promote migration of human trophoblast. We aimed to localize specific chemokine receptors in human first trimester tissue, and to determine whether trophoblast migration could be stimulated by the endometrium and by chemokines. Cellular localisation of specific receptors was assessed by immunohistochemistry in human first trimester implantation sites. Using an in vitro assay, trophoblast migration was assessed in response to human endometrial epithelial (HEEC) and decidualised stromal cells (DESC) (serum-free) conditioned medium and to recombinant human FKN, MCP-3, HCC-1 and MIP-1β. CX3CR1 and CCR1 protein was localised to the vascular extravillous trophoblast (EVTs), but not to the invading interstitial EVTs, with weak staining on the syncytium. Significant migration of cells occurred in response to conditioned media from HEEC and DESC. FKN, MIP-1β and HCC-1, but not MCP-3 also promoted significant trophoblast migration. Neutralizing antibodies for FKN and MIP-1β but not MCP-3 significantly reduced migration to conditioned media, indicating that at least these two chemokines contributed to the effects. These data support a role for endometrial derived chemokines in promoting human trophoblast migration. (1)Jones et al. (2004). JCEM 89(12), 6155–6167.(2)Hannan et al. (2004). Reprod. Fert. Devel. 16(Suppl.), A225, p. 78.(3)Hannan et al. (2004). JCEM 89(12), 6119–6129.

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