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.

scholarly journals MRI analysis of angiogenesis during mouse embryo implantation

2006 ◽  
Vol 55 (5) ◽  
pp. 1013-1022 ◽  
Author(s):  
Vicki Plaks ◽  
Vyacheslav Kalchenko ◽  
Nava Dekel ◽  
Michal Neeman
Keyword(s):  
Mouse Embryo ◽  
Embryo Implantation

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.

scholarly journals Effect of 32/67 kDa laminin-binding protein antibody on mouse embryo implantation

Reproduction ◽  
2000 ◽  
Vol 119 (1) ◽  
pp. 137-142 ◽  
Author(s):  
C Zhang ◽  
E Duan ◽  
Y Cao ◽  
G Jiang ◽  
G Zeng
Keyword(s):  
Mouse Embryo ◽  
Binding Protein ◽  
Embryo Implantation ◽  
Laminin Binding Protein ◽  
Laminin Binding

scholarly journals Progesterone-regulated Hsd11b2 as a barrier to balance mouse uterine corticosterone

2020 ◽  
Vol 244 (1) ◽  
pp. 177-187 ◽  
Author(s):  
Hong-Tao Zheng ◽  
Tao Fu ◽  
Hai-Yi Zhang ◽  
Zhen-Shan Yang ◽  
Zhan-Hong Zheng ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Mouse Embryo ◽  
Stromal Cells ◽  
Inner Cell Mass ◽  
Local Level ◽  
Embryo Implantation ◽  
Cell Mass ◽  
Type I ◽  
Mouse Uterus ◽  
Ovariectomized Mice

Glucocorticoids (GCs) are essential for mouse embryo implantation and decidualization. Excess GCs are harmful for mouse embryo implantation and decidualization. 11β-Hydroxysteroid dehydrogenases type I and II (Hsd11b1/Hsd11b2) are main enzymes for regulating local level of GCs. Hsd11b2 acts as the placental glucocorticoid barrier to protect the fetus from excessive exposure. Although effects of GCs on the fetus and placenta in late pregnancy have been extensively studied, the effects of these adrenal corticosteroids in early pregnancy are far less well defined. Therefore, we examined the expression, regulation and function of Hsd11b1/Hsd11b2 in mouse uterus during early pregnancy. We found that Hsd11b2 is highly expressed in endometrial stromal cells on days 3 and 4 of pregnancy and mainly upregulated by progesterone (P4). In both ovariectomized mice and cultured stromal cells, P4 significantly stimulates Hsd11b2 expression. P4 stimulation of Hsd11b2 is mainly mediated by the Ihh pathway. The uterine level of corticosterone (Cort) is regulated by Hsd11b2 during preimplantation. Embryo development and the number of inner cell mass cells are suppressed by Cort treatment. These results indicate that P4 should provide a low Cort environment for the development of preimplantation mouse embryos by promoting the expression of uterine Hsd11b2.

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.

The expression and function of cystatin C and cathepsin B and cathepsin L during mouse embryo implantation and placentation

Development ◽  
1997 ◽  
Vol 124 (17) ◽  
pp. 3415-3425
Author(s):  
S. Afonso ◽  
L. Romagnano ◽  
B. Babiarz
Keyword(s):  
Cystatin C ◽  
Mouse Embryo ◽  
Cathepsin B ◽  
Proteinase Inhibitors ◽  
Cathepsin L ◽  
Embryo Implantation ◽  
Giant Cells ◽  
Major Product ◽  
Normal Embryo ◽  
And Function

The implantation of the mouse embryo requires the controlled invasion of the uterine stroma by the embryonic trophoblast. This event is dependent, in part, on the secretion of matrix metalloproteinases and serine proteinases for the extracellular degradation of the uterine matrix. Proteinase activity is controlled by stromal decidualization and specific proteinase inhibitors. This work adds to our understanding of implantation and placentation by reporting the expression and function of another class of proteinases/inhibitors closely related to invasive cell behavior. We focused on the cysteine proteinases, cathepsins B and L, and their inhibitor cystatin C. Northern blots showed that trophoblast expressed cathepsin B throughout the invasive period (days 5.5-10.5). Both cathepsin B message and cathepsin L protein were localized to the mature, invasive trophoblast giant cells. Substrate gel electrophoresis showed an increase in giant cell cathepsin activity with enzyme profiles changing at the end of the invasive period. Northern and western blotting showed that cystatin C, the main inhibitor of cathepsins, was a major product of the decidualizing stroma. Message levels first increased in peripheral decidualizing cells, with the protein localizing close to the embryo during implantation (days 5.5-8.5). With the regression of the decidua beginning on day 9.5, a coordinated upregulation of both cathepsin B and cystatin C was observed implying a role for controlled cathepsin expression during apoptosis. E-64, a synthetic inhibitor of cathepsins B and L, was injected into pregnant females at the stage of blastocyst attachment (days 4.5-5.5). High doses resulted in the complete failure of implantation while lower doses resulted in stunted embryos and a reduced decidual reaction. These results suggested that cathepsins B and L are necessary for normal embryo development and uterine decidualization, and that decidua contributes to their control by a coordinated expression of cystatin C within the implantation site.

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