scholarly journals Role of adipokines in embryo implantation

2021 ◽  
Author(s):  
Davoud Jafari-Gharabaghlou ◽  
Mostafa Vaghari-Tabari ◽  
Hajar Oghbaei ◽  
Laura Lotz ◽  
Reza Zarezadeh ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Complex Process ◽  
Strict Regulation ◽  
Implantation Process ◽  
Maternal Fetal Transmission ◽  
Multiple Molecules

Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo-maternal cross-talk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo-maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.

ADF/n-cofilin–dependent actin turnover determines platelet formation and sizing

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1767-1775 ◽  
Author(s):  
Markus Bender ◽  
Anita Eckly ◽  
John H. Hartwig ◽  
Margitta Elvers ◽  
Irina Pleines ◽  
...  
Keyword(s):  
Actin Filament ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Actin Dynamics ◽  
Complex Process ◽  
First Time ◽  
Late Stages ◽  
Platelet Formation

Abstract The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubules are the main structural component of proplatelets and microtubule sliding is known to drive proplatelet elongation, the role of actin dynamics in the process of platelet formation has remained elusive. Here, we tailored a mouse model lacking all ADF/n-cofilin–mediated actin dynamics in megakaryocytes to specifically elucidate the role of actin filament turnover in platelet formation. We demonstrate, for the first time, that in vivo actin filament turnover plays a critical role in the late stages of platelet formation from megakaryocytes and the proper sizing of platelets in the periphery. Our results provide the genetic proof that platelet production from megakaryocytes strictly requires dynamic changes in the actin cytoskeleton.

scholarly journals Uterine SOX17: a key player in human endometrial receptivity and embryo implantation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sophie Kinnear ◽  
Lois A. Salamonsen ◽  
Mathias Francois ◽  
Vincent Harley ◽  
Jemma Evans
Keyword(s):  
Epithelial Cells ◽  
Clinical Investigation ◽  
Embryo Implantation ◽  
Adhesive Contact ◽  
Endometrial Receptivity ◽  
Large Numbers ◽  
Yin And Yang ◽  
Hormonal Milieu ◽  
Endometrial Epithelial Cells

Abstract The yin and yang of female fertility is a complicated issue; large numbers of women/couples desire fertility and seek assisted reproduction intervention to achieve conception, while others seek to prevent pregnancy. Understanding specific molecules which control endometrial-embryo interactions is essential for both facilitating and preventing pregnancy. SOX17 has recently emerged as an important transcription factor involved in endometrial receptivity and embryo implantation. However, studies to date have examined mouse models of pregnancy which do not necessarily translate to the human. Demonstration of a role for ‘implantation factors’ in a human system is critical to provide a rationale for in depth clinical investigation and targeting of such factors. We demonstrate that SOX17is present within the receptive human endometrium and is up-regulated within human endometrial epithelial cells by combined estrogen & progesterone, the hormonal milieu during the receptive window. SOX17 localizes to the point of adhesive contact between human endometrial epithelial cells and a human ‘embryo mimic’ model (trophectodermal spheroid). Targeting SOX17 in endometrial epithelial cells using CRISPR/Cas9 knockdown or a SOX-F family inhibitor, MCC177, significantly inhibited adhesion of an trophectodermal spheroids to the epithelial cells thereby preventing ‘implantation’. These data confirm the important role of endometrial SOX17 in human endometrial receptivity and embryo implantation.

scholarly journals Ssc-miR-21-5p regulates endometrial epithelial cell proliferation, apoptosis and migration via the PDCD4/AKT pathway

2020 ◽  
Vol 133 (23) ◽  
pp. jcs248898
Author(s):  
Renwu Hua ◽  
Xiuling Zhang ◽  
Wenchao Li ◽  
Weisi Lian ◽  
Qiaorui Liu ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Vital Role ◽  
Endometrial Receptivity ◽  
Akt Pathway ◽  
Loss Of Function ◽  
Endometrial Epithelial Cell ◽  
Programmed Cell Death 4 ◽  
And Migration

ABSTRACTEndometrial receptivity plays a vital role in successful embryo implantation in pigs. MicroRNAs (miRNAs), known as regulators of gene expression, have been implicated in the regulation of embryo implantation. However, the role of miRNAs in endometrial receptivity during the pre-implantation period remains elusive. In this study, we report that the expression level of Sus scrofa (ssc)-miR-21-5p in porcine endometrium tissues was significantly increased from day 9 to day 12 of pregnancy. Knockdown of ssc-miR-21-5p inhibited proliferation and migration of endometrial epithelial cells (EECs), and induced their apoptosis. We verified that programmed cell death 4 (PDCD4) was a target gene of ssc-miR-21-5p. Inhibition of PDCD4 rescued the effect of ssc-miR-21-5p repression on EECs. Our results also revealed that knockdown of ssc-miR-21-5p impeded the phosphorylation of AKT (herein referring to AKT1) by targeting PDCD4, which further upregulated the expression of Bax, and downregulated the levels of Bcl2 and Mmp9. Furthermore, loss of function of Mus musculus (mmu)-miR-21-5p in vivo resulted in a decreased number of implanted mouse embryos. Taken together, knockdown of ssc-miR-21-5p hampers endometrial receptivity by modulating the PDCD4/AKT pathway.

Current studies on human implantation: a brief overview

1995 ◽  
Vol 7 (6) ◽  
pp. 1395 ◽  
Author(s):  
PA Rogers
Keyword(s):  
Animal Models ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Biochemical Changes ◽  
Human Studies ◽  
Complex Interactions ◽  
Complex Process ◽  
Wide Range ◽  
Human Implantation

Embryo implantation involves a series of complex interactions between the developing embryo and the maternal endometrium. Results of studies with animal models suggest that the uterus must undergo a series of morphological and biochemical changes, mediated primarily by oestrogen and progesterone, before it becomes receptive for successful implantation. At present there is little understanding of the endometrial changes required to achieve endometrial receptivity for implantation in the human. It appears that control of receptivity is not as stringent in the human as in some other species, with IVF data suggesting that the duration of receptivity is at least 4 days, and that successful implantation can occur under a relatively wide range of morphological and ultrastructural conditions. Research on the later stages of implantation, including embryo positioning within the uterus, attachment and invasion, has been almost non-existent in the human. Further studies are critical for a better understanding of this complex process, although human studies will always be limited by ethical constraints.

GRIM-19, a gene associated with retinoid-interferon-induced mortality, affects endometrial receptivity and embryo implantation

2017 ◽  
Vol 29 (7) ◽  
pp. 1447 ◽  
Author(s):  
Yang Yang ◽  
Yanyan Sun ◽  
Laiyang Cheng ◽  
Anna Li ◽  
Yanjun Shen ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Embryo Implantation ◽  
Pregnant Mouse ◽  
Endometrial Receptivity ◽  
Mrna Levels ◽  
Protein Levels ◽  
Tnf Α ◽  
Pregnant Mice ◽  
Adhesion Rate

GRIM-19 is associated with apoptosis, abnormal proliferation, immune tolerance and malignant transformation, and it also plays an important role in early embryonic development. Although the homologous deletion of GRIM-19 causes embryonic lethality in mice, the precise role of GRIM-19 in embryo implantation has not been elucidated. Here we show that GRIM-19 plays an important role in endometrial receptivity and embryo implantation. Day 1 to Day 6 pregnant mouse uteri were collected. Immunohistochemistry studies revealed the presence of GRIM-19 on the luminal epithelium and glandular epithelium throughout the implantation period in pregnant mice. The protein and mRNA levels of GRIM-19 were markedly decreased on Day 4 of pregnancy in pregnant mice, but there was no change in GRIM-19 levels in a group of pseudopregnant mice. Overexpression of GRIM-19 decreased the adhesion rate of RL95–2–BeWo co-cultured spheroids and increased apoptosis. Furthermore, STAT3 and IL-11 mRNA and protein levels were reduced by overexpressing GRIM-19, but protein and mRNA levels of TNF-α were increased. These findings indicate the involvement of GRIM-19 in the embryo implantation process by regulating adhesion, apoptosis and immune tolerance.

scholarly journals 90 YEARS OF PROGESTERONE: New insights into progesterone receptor signaling in the endometrium required for embryo implantation

2020 ◽  
Vol 65 (1) ◽  
pp. T1-T14 ◽  
Author(s):  
Francesco J DeMayo ◽  
John P Lydon
Keyword(s):  
Progesterone Receptor ◽  
Nuclear Receptor ◽  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Crystalline Form ◽  
Functional Connection ◽  
Genome Wide ◽  
Molecular Landscape ◽  
Selection Of

Progesterone’s ability to maintain pregnancy in eutherian mammals highlighted this steroid as the ‘hormone of pregnancy’. It was the unique ‘pro-gestational’ bioactivity of progesterone that enabled eventual purification of this ovarian steroid to crystalline form by Willard Myron Allen in the early 1930s. While a functional connection between normal progesterone responses (’progestational proliferation’) of the uterus with the maintenance of pregnancy was quickly appreciated, an understanding of progesterone’s involvement in the early stages of pregnancy establishment was comparatively less well understood. With the aforementioned as historical backdrop, this review focuses on a selection of key advances in our understanding of the molecular mechanisms by which progesterone, through its nuclear receptor (the progesterone receptor), drives the development of endometrial receptivity, a transient uterine state that allows for embryo implantation and the establishment of pregnancy. Highlighted in this review are the significant contributions of advanced mouse engineering and genome-wide transcriptomic and cistromic analytics which reveal the pivotal molecular mediators and modifiers that are essential to progesterone-dependent endometrial receptivity and decidualization. With a clearer understanding of the molecular landscape that underpins uterine responsiveness to progesterone during the periimplantation period, we predict that common gynecologic morbidities due to abnormal progesterone responsiveness will be more effectively diagnosed and/or treated in the future.

scholarly journals Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?

2019 ◽  
Vol 20 (15) ◽  
pp. 3822 ◽  
Author(s):  
Ryan M. Marquardt ◽  
Tae Hoon Kim ◽  
Jung-Ho Shin ◽  
Jae-Wook Jeong
Keyword(s):  
Pelvic Pain ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Uterine Cavity ◽  
Endometrial Receptivity ◽  
Estrogen Signaling ◽  
Normal Menstrual Cycle ◽  
Hormone Imbalance ◽  
Dynamic Interplay

In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily through their cognate receptors to set off cascades of signaling pathways and enact large-scale gene expression programs. In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance. This hormone imbalance leads to heightened inflammation and may also increase the pelvic pain of the disease and decrease endometrial receptivity to embryo implantation. This review focuses on the molecular mechanisms governing progesterone and estrogen signaling supporting endometrial function and how they become dysregulated in endometriosis. Understanding how these mechanisms contribute to the pelvic pain and infertility associated with endometriosis will open new avenues of targeted medical therapies to give relief to the millions of women suffering its effects.

scholarly journals Influence of hyaluronan on endometrial receptivity and embryo attachment in sheep

2017 ◽  
Vol 29 (9) ◽  
pp. 1763 ◽  
Author(s):  
Waleed F. A. Marei ◽  
D. Claire Wathes ◽  
Kabir A. Raheem ◽  
Omnia Mohey-Elsaeed ◽  
Fataneh Ghafari ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Uterine Receptivity ◽  
Female Reproduction ◽  
Mucin 1 ◽  
Synthesis Inhibitor ◽  
The Impact ◽  
Hyaluronidase 2 ◽  
Embryo Attachment

An increasing number of reports suggests a role of hyaluronan (HA) in female reproduction and interest in its application in assisted reproduction is rising. However, there are contrasting data about the effectiveness of adding HA to the embryo-transfer medium on improving pregnancy rates. Using sheep as an experimental model, the studies reported here analysed the impact of HA infusion into the uterus on embryo attachment to uterine luminal epithelium (LE) and expression of selected markers of uterine receptivity. On Day 14 after natural mating (pre-attachment), uterine horns were infused with either (n = 4 each): PBS (control), HA (1 mg mL–1), HA + hyaluronidase 2 (Hyal2; 300 IU mL–1) or 4-methyl-umbelliferone (HA-synthesis inhibitor; 4MU, 1 mM). HA immunostaining on uterine sections collected on Day 17 was negative in the 4MU group and weak in the HA+Hyal2 group. In contrast to 4MU, which resulted in 100% attachment, HA infusion blocked embryo attachment in all treated animals. This was accompanied by the disappearance of mucin 1 and increased expression of osteopontin and CD44v6 in the LE of uteri with attached embryos. In conclusion, the presence of HA at the embryo–maternal interface during embryo implantation resulted in reduced endometrial receptivity and inhibited the interaction of trophoblasts with the LE, whereas clearance of HA favoured embryo attachment.

scholarly journals Expression and function of Pdcd4 in mouse endometrium during early pregnancy

Reproduction ◽  
2018 ◽  
Vol 155 (4) ◽  
pp. 393-402 ◽  
Author(s):  
Yue Zhang ◽  
Mingyun Ni ◽  
Na Liu ◽  
Yongjiang Zhou ◽  
Xuemei Chen ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Quantitative Polymerase Chain Reaction ◽  
Embryo Implantation ◽  
Complex Process ◽  
Programmed Cell Death 4 ◽  
Implantation Sites ◽  
And Function

Embryo implantation is a complex process involving synchronised crosstalk between a receptive endometrium and functional blastocysts. Apoptosis plays an important role in this process as well as in the maintenance of pregnancy. In this study, we analysed the expression pattern of programmed cell death 4 (Pdcd4), a gene associated with apoptosis in the mouse endometrium, during early pregnancy and pseudopregnancy by real-time quantitative polymerase chain reaction, in situ hybridisation, Western blotting and immunohistochemistry. The results showed that Pdcd4 was increased along with days of pregnancy and significantly reduced at implantation sites (IS) from day 5 of pregnancy (D5). The level of Pdcd4 at IS was substantially lower than that at interimplantation sites (IIS) on D6 and D7. In addition, Pdcd4 expression in the endometrium was reduced in response to artificially induced decidualisation in vivo and in vitro. Downregulation of Pdcd4 gene expression in cultured primary stromal cells promoted decidualisation, while upregulation inhibited the decidualisation process by increasing apoptosis. These results demonstrate that Pdcd4 is involved in stromal cell decidualisation by mediating apoptosis and therefore plays a role in embryo implantation in mice.

scholarly journals Differential MicroRNA Expression Involved in Endometrial Receptivity of Goats

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 472
Author(s):  
Xupeng Zang ◽  
Chen Zhou ◽  
Wenjing Wang ◽  
Jianyu Gan ◽  
Yaokun Li ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Fish Analysis ◽  
Factors Affecting ◽  
Mirna Expression Profiles ◽  
Differentially Expressed Mirnas

Endometrial receptivity represents one of the leading factors affecting the successful implantation of embryos during early pregnancy. However, the mechanism of microRNAs (miRNAs) to establish goat endometrial receptivity remains unclear. This study was intended to identify potential miRNAs and regulatory mechanisms associated with establishing endometrial receptivity through integrating bioinformatics analysis and experimental verification. MiRNA expression profiles were obtained by high-throughput sequencing, resulting in the detection of 33 differentially expressed miRNAs (DEMs), followed by their validation through quantitative RT-PCR. Furthermore, 10 potential transcription factors (TFs) and 1316 target genes of these DEMs were obtained, and the TF–miRNA and miRNA–mRNA interaction networks were constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these miRNAs were significantly linked to establishing endometrial receptivity. Moreover, the fluorescence in situ hybridization (FISH) analysis, dual-luciferase report assay, and immunohistochemistry (IHC) analysis corroborated that chi-miR-483 could directly bind to deltex E3 ubiquitin ligase 3L (DTX3L) to reduce its expression level. In conclusion, our findings contribute to a better understanding of molecular mechanisms regulating the endometrial receptivity of goats, and they provide a reference for improving embryo implantation efficiency.

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