scholarly journals Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems

2020 ◽  
Vol 21 (5) ◽  
pp. 1885 ◽  
Author(s):  
Hiroshi Fujiwara ◽  
Masanori Ono ◽  
Yukiyasu Sato ◽  
Kazuhiko Imakawa ◽  
Takashi Iizuka ◽  
...  
Keyword(s):  
Degradation Products ◽  
Embryo Implantation ◽  
Endocrine System ◽  
Control Mechanisms ◽  
Successful Pregnancy ◽  
Maternal Tissue ◽  
Sex Steroid Hormone ◽  
Repulsive Forces ◽  
Inhibitory Molecules ◽  
Further Development

Embryo implantation in the uterus is an essential process for successful pregnancy in mammals. In general, the endocrine system induces sufficient embryo receptivity in the endometrium, where adhesion-promoting molecules increase and adhesion-inhibitory molecules decrease. Although the precise mechanisms remain unknown, it is widely accepted that maternal–embryo communications, including embryonic signals, improve the receptive ability of the sex steroid hormone-primed endometrium. The embryo may utilize repulsive forces produced by an Eph–ephrin system for its timely attachment to and subsequent invasion through the endometrial epithelial layer. Importantly, the embryonic signals are considered to act on maternal immune cells to induce immune tolerance. They also elicit local inflammation that promotes endometrial differentiation and maternal tissue remodeling during embryo implantation and placentation. Additional clarification of the immune control mechanisms by embryonic signals, such as human chorionic gonadotropin, pre-implantation factor, zona pellucida degradation products, and laeverin, will aid in the further development of immunotherapy to minimize implantation failure in the future.

Delayed implantation induced by letrozole in mice

2021 ◽  
Author(s):  
Fang Wang ◽  
Shijie Li ◽  
Lingshuai Meng ◽  
Ye Kuang ◽  
Zhonghua Liu ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Late Pregnancy ◽  
High Dose ◽  
Successful Pregnancy ◽  
Short Delay ◽  
Wild Mice ◽  
Plasma Progesterone ◽  
Delayed Implantation ◽  
Gene Ablation ◽  
At Will

Implantation timing is key for a successful pregnancy. Short delay in embryo implantation caused by targeted gene ablation produced a cascading problem in the later stages of the pregnancy. Although several delayed implantation models have been established in wild mice, almost none of them is suitable for investigating the delay on the late events of pregnancy. Here, we report a new delayed implantation model established by the intraperitoneally administration of letrozole at 5 mg/kg body weight on the day 3 of pregnancy. In these mice, initiation of implantation was induced at will by the injection of estradiol (E2). When the estradiol (3 ng) was injected on day 4 of pregnancy (i.e., without delay), the embryo implantation restarted, and the pregnancy continued normally. However, high dose of estrogen (25 ng) caused compromised implantation. We also found that only 67% of the female mice could be pregnant normally and finally gave birth when the injection of estradiol (3 ng) was on day 5 of pregnancy (i.e., one day delay). Most of the failed pregnancies had impaired decidualization, decreased plasma progesterone levels and compromised angiogenesis. Progesterone supplementation could rescue decidualization failure in the mice. Collectively, we established a new model of delayed implantation by letrozole, which can be easily used to study the effect and mechanisms of delay of embryo implantation on the progression of late pregnancy events.

scholarly journals 226.Regulated expression of adhesion and anti-adhesion molecules in mouse endometrium during early pregnancy

2004 ◽  
Vol 16 (9) ◽  
pp. 226 ◽  
Author(s):  
M. J. Jasper ◽  
A. Stocker ◽  
S. A. Robertson
Keyword(s):  
Real Time ◽  
Adhesion Molecules ◽  
Early Pregnancy ◽  
Embryo Implantation ◽  
Early Embryo ◽  
Luminal Epithelium ◽  
Paracrine Factors ◽  
Mean Values ◽  
Actin Mrna ◽  
Further Development

To implant and establish the connections that are vital for further development, the early embryo must attach to and then breech the barrier posed by the epithelium of the maternal tract. Expression of adhesion and anti-adhesion molecules in the luminal epithelium of the endometrium are thought to fluctuate in a temporal pattern to 'frame' the implantation site, with their expression regulated by endocrine and paracrine factors. Anti-adhesion molecules, such as members of the mucin family, provide a barrier to implantation in sites or at times unsuitable for embryo development. Expression of adhesion molecules, or specific integrins, are thought to aid in the adhesion of the embryo, allowing it to induce changes in the underlying tissue promoting embryo invasion and pregnancy. The aim of this study was to quantitate the expression of mRNA encoding the integrins αυ, α4 and β3 and MUC1 and MUC4 from Day 0 (oestrous) to Day 4 of pregnancy (implantation) using quantitative real time RT-PCR. Uterine tissues were collected at oestrous and at Days 1, 2, 3 and 4 of pregnancy (Day 1 corresponding to the presence of a vaginal plug), total RNA was extracted, DNAse treated, reverse transcribed into cDNA, and quantified by real-time PCR using SYBR Green chemistry. All specific primers were designed using GenBank sequences and data were normalised to β-actin mRNA expression. Expression of MUC1 and MUC4 mRNAs was dramatically reduced, with mean values 20-fold and 100-fold less than at oestrous respectively, by Day 4 of pregnancy. In contrast, expression of mRNAs encoding integrins αυ, α4 and β3 was detected throughout early pregnancy. These data demonstrate that adhesion and anti-adhesion molecules are differentially expressed in the murine uterus during early pregnancy and may be key mediators in embryo implantation, promoting attachment of the embryo to the luminal epithelium in an environment conducive to embryo growth and development. Supported by a Clive & Vera Ramaciotti Project Grant to MJ Jasper.

Immune System Cooperatively Supports Endocrine System-Primed Embryo Implantation

2009 ◽  
Vol 26 (3) ◽  
pp. 122-128 ◽  
Author(s):  
Hiroshi Fujiwara ◽  
Atsushi Ideta ◽  
Yoshihiko Araki ◽  
Yumi Takao ◽  
Yukiyasu Sato ◽  
...  
Keyword(s):  
Immune System ◽  
Embryo Implantation ◽  
Endocrine System

scholarly journals Decidual Interleukin-22-Producing CD4+ T Cells (Th17/Th0/IL-22+ and Th17/Th2/IL-22+, Th2/IL-22+, Th0/IL-22+), Which Also Produce IL-4, Are Involved in the Success of Pregnancy

2019 ◽  
Vol 20 (2) ◽  
pp. 428 ◽  
Author(s):  
Federica Logiodice ◽  
Letizia Lombardelli ◽  
Ornela Kullolli ◽  
Herman Haller ◽  
Enrico Maggi ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Cd4 Cells ◽  
Pathogenic Role ◽  
Successful Pregnancy ◽  
Interleukin 22 ◽  
Ifn Γ

Trophoblast expressing paternal HLA-C resembles a semiallograft, and could be rejected by maternal T cells. IL-22 seems to be involved in allograft rejection and thus could be responsible for miscarriages. We examined the role of decidual IL-22-producing CD4+ T on human pregnancy. In those experiencing successful pregnancy and those experiencing unexplained recurrent abortion (URA), the levels of IL-22 produced by decidual CD4+ T cells are higher than those of peripheral blood T cells. We found a correlation of IL-22 and IL-4 produced by decidual CD4+ T cells in those experiencing successful pregnancy, not in those experiencing URA. The correlation of IL-22 and IL-4 was also found in the serum of successful pregnancy. A prevalence of CD4+ T cells producing IL-22 and IL-4 (Th17/Th2/IL-22+, Th17/Th0/IL-22+, Th17/Th2/IL-22+, and Th0/IL-22+ cells) was observed in decidua of those experiencing successful pregnancy, whereas Th17/Th1/IL-22+ cells, which do not produce IL-4, are prevalent in those experiencing URA. Th17/Th2/IL-22+ and Th17/Th0/IL-22+ cells are exclusively present at the embryo implantation site where IL-4, GATA-3, IL-17A, ROR-C, IL-22, and AHR mRNA are expressed. T-bet and IFN-γ mRNA are found away from the implantation site. There is no pathogenic role of IL-22 when IL-4 is also produced by decidual CD4+ cells. Th17/Th2/IL-22+ and Th17/Th0/IL-22+ cells seem to be crucial for embryo implantation.

scholarly journals CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hwa Seon Koo ◽  
Min-Ji Yoon ◽  
Seon-Hwa Hong ◽  
Jungho Ahn ◽  
Hwijae Cha ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Therapeutic Strategy ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Successful Pregnancy ◽  
Vessel Formation ◽  
Evidence Based Treatments ◽  
Chemokine Cxcl12 ◽  
Cd34 Expression

AbstractSuccessful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention. Chemokine CXCL12 derived from pre- and peri-implanting embryos significantly enhances the rates of embryo attachment and promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in C57BL/6 mice improved endometrial receptivity showing increased integrin β3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Thus, our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a minimally-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

scholarly journals Accumulation of Securin on Spindle During Female Meiosis I

2021 ◽  
Vol 9 ◽  
Author(s):  
Tereza Pauerova ◽  
Lenka Radonova ◽  
Adela Horakova ◽  
Jason G. Knott ◽  
Martin Anger
Keyword(s):  
Chromosome Segregation ◽  
Specific Protein ◽  
Control Mechanisms ◽  
Cyclin Dependent Kinase ◽  
Tight Control ◽  
Female Meiosis ◽  
Sister Chromatids ◽  
Endogenous Protein ◽  
Further Development ◽  
Meiosis I

Chromosome segregation during female meiosis is frequently incorrect with severe consequences including termination of further development or severe disorders, such as Down syndrome. Accurate chromosome segregation requires tight control of a protease called separase, which facilitates the separation of sister chromatids by cohesin cleavage. There are several control mechanisms in place, including the binding of specific protein inhibitor securin, phosphorylation by cyclin-dependent kinase 1 (CDK1), and complex with SGO2 and MAD2 proteins. All these mechanisms restrict the activation of separase for the time when all chromosomes are properly attached to the spindle. In our study, we focused on securin and compared the expression profile of endogenous protein with exogenous securin, which is widely used to study chromosome segregation. We also compared the dynamics of securin proteolysis in meiosis I and meiosis II. Our study revealed that the expression of both endogenous and exogenous securin in oocytes is compartmentalized and that this protein accumulates on the spindle during meiosis I. We believe that this might have a direct impact on the regulation of separase activity in the vicinity of the chromosomes.

scholarly journals Kruppel-like factor 5 (Klf5) in fetal-maternal tissue during periimplantation and effects of ovarian steroid hormone antagonist on its expression during uterine receptivity of albino mice

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Kanmuna Ray Talukdar ◽  
Purbajyoti Saikia ◽  
Hirendra N. Sarma
Keyword(s):  
Western Blot ◽  
Embryo Implantation ◽  
Experimental Period ◽  
Glandular Epithelium ◽  
Independent Factor ◽  
Uterine Receptivity ◽  
Ovarian Steroid ◽  
Maternal Tissue ◽  
Ovarian Steroids ◽  
Albino Mice

Abstract Background Embryo implantation is a tightly regulated sequence of events regulated by ovarian steroids, estrogen and progesterone, and their downstream targets. Ovarian steroids regulate most of the genes involved in embryo implantation and pregnancy. However, some factors are not regulated by ovarian steroids, estrogen, progesterone, or both. Kruppel-like factor 5 (Klf5) is an example of an ovarian steroid–independent factor having a role in cellular proliferation, differentiation. The detailed expression profile of Klf5 during uterine receptivity and periimplantation has not been studied till now. In the present research work, an attempt was made to investigate the expression pattern of Klf5 in mice fetal-maternal tissue during periimplantation (day 4–day 8). The expressional and functional independence of Klf5 on the ovarian steroids was studied using estrogen and progesterone antagonist. The study was carried out in female Swiss albino mice of LACA strain during the periimplantation period. KLF5 was localized in the fetal-maternal tissues using the immunofluorescence technique in paraffin-embedded tissues. Ovarian steroid antagonists were administered subcutaneously from day 1 to day 3 of gestation, and the uterus was collected on the morning of day 4. Klf5 protein and mRNA levels were studied by western blot and quantitative real-time PCR (qPCR), respectively. Results KLF5 was localized in the embryo, uterine luminal epithelium, glandular epithelium, and proliferating stromal cells during periimplantation. In ovarian steroid antagonist–treated groups, KLF5 was localized in the luminal and glandular epithelium and stroma. Western blot and qPCR confirmed translation and transcription of KLF5 during the experimental period. The KLF5 protein level significantly increased on day 6, day 7, and day 8 when compared with day 4 (P < 0.05). The mRNA level of Klf5 increased significantly on day 7 and day 8 when compared with day 4 (P < 0.05). In ovarian steroid antagonist–treated groups, protein and mRNA corresponding to Klf5 were observed. From this finding, it can be assumed that Klf5 may be a steroid-independent factor expressed during uterine receptivity. Conclusion Spatiotemporal KLF5 expression in fetal-maternal tissue was observed during the experimental period. The results suggest that Klf5 is an ovarian steroid–independent factor that may play a pivotal role in implantation, decidualization, and embryogenesis.

scholarly journals Inherited thrombophilia: a double-edged sword

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Saskia Middeldorp
Keyword(s):  
Pregnancy Complications ◽  
Arterial Thrombosis ◽  
Embryo Implantation ◽  
Factor V Leiden ◽  
Coagulation Disorder ◽  
Factor V ◽  
Successful Pregnancy ◽  
Inherited Thrombophilia ◽  
Sperm Counts ◽  
Blood Coagulation Disorder

AbstractInherited thrombophilia is a blood coagulation disorder that increases the risk for venous thromboembolism (VTE). During the last decades, the practice of testing has evolved from testing selected populations, leading to high perceived risks, to broad testing for various conditions that included VTE, arterial thrombosis, and pregnancy complications. Because results of such tests usually do not guide treatment decisions, not testing patients with VTE for inherited thrombophilia is on the “Choosing Wisely” list endorsed by multiple specialty societies, including ASH. Inherited thrombophilia can be regarded a double-edged sword, as despite the rationale not to test, it is still being performed frequently. Another way of seeing inherited thrombophilia as a double-edged sword lies in its 2-sided association with reproduction, both in men and in women. Current areas of research are whether women with inherited thrombophilia and pregnancy complications benefit from anticoagulant therapy with regard to improving the chance of a successful pregnancy. Potential effects of inherited thrombophilia, most notably factor V Leiden, on improved embryo implantation in women and sperm counts in men are intriguing, but are currently poorly understood.

Evolution of manifestos in a developing parliamentary democracy with proportional representation and multiparty coalition governments

2016 ◽  
Vol 24 (3) ◽  
pp. 296-306
Author(s):  
Samo Kropivnik ◽  
Simona Kustec Lipicer
Keyword(s):  
Political Parties ◽  
Political System ◽  
Electoral System ◽  
Control Mechanisms ◽  
Parliamentary Democracy ◽  
Political Struggle ◽  
Coalition Governments ◽  
Democratic Systems ◽  
Further Development ◽  
Issue Emphasis

In exploring the first two decades of evolution of political programmes applied for the electoral processes in Slovenia, a young European multiparty parliamentary democracy with a proportional electoral system and multiparty government coalitions, the article contributes to a rich tradition of studying the programmes of political parties as relevant narrators of the development of democratic systems and suggests an answer to ‘why do parties write manifestos?’ The main findings include the distinct issue emphasis of parliamentary and non-parliamentary parties’ manifestos and convergence in issue emphasis over time among parliamentary parties who go on to form coalition governments. Regarding the ‘why’, these and other findings indicate that the manifestos considered here are intended more for post-election purposes – in particular, for the formation of alliances and negotiating and running a coalition government – than for attracting voters in the pre-election period. Party programmes are seen more as self-intended tools for political struggle than as promoters or control mechanisms for the further development of the democratic political system.

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