scholarly journals Regulation of homeobox A10 expression in the primate endometrium by progesterone and embryonic stimuli

Reproduction ◽  
2007 ◽  
Vol 134 (3) ◽  
pp. 513-523 ◽  
Author(s):  
G B Godbole ◽  
D N Modi ◽  
C P Puri
Keyword(s):  
Growth Factor ◽  
Luteal Phase ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Macaca Radiata ◽  
Endometrial Cells ◽  
Preimplantation Stage ◽  
Bonnet Monkey ◽  
Embryonic Signaling

Homeobox A10 (HOXA10), a member of abdominal B subclass of homeobox genes, is responsible for uterine homeosis during development. Intriguingly, in the adult murine uterus, HOXA10 has been demonstrated to play important roles in receptivity, embryo implantation, and decidualization. However, the roles of HOXA10 in the primate endometrium are not known. To gain insights into the roles of HOXA10 in the primate endometrium, its expression was studied in the endometria of bonnet monkey (Macaca radiata) in the receptive phase and also in the endometria of monkeys treated with antiprogestin onapristone (ZK98.299) or in conception cycle where the presence of preimplantation stage blastocyst was verified. In addition, the mRNA expression of HOXA11 and insulin-like growth factor-binding protein 1 (IGFBP1) was evaluated by real-time PCR in these animals.The results revealed that HOXA10 in the luteal phase primate endometrium is differentially expressed in the functionalis and the basalis zones, which is modulated in vivo by progesterone and also by the signals from the incoming embryo suggesting the involvement of HOXA10 in the process of establishment of pregnancy in primates. In addition, the results also demonstrated that the expression of IGFBP1 but not HOXA11 is coregulated with HOXA10 in the endometria of these animals. The pattern of changes in the expression of HOXA10 in response to the two stimuli suggests that endometrial receptivity and implantation not only requires a synchrony of maternal and embryonic signaling on endometrial cells in the primates but there also exists a controlled differential response among the cells of various uterine compartments.

scholarly journals miR-183-5p regulates uterine receptivity and enhances embryo implantation

2020 ◽  
Vol 64 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Rubab Akbar ◽  
Kamran Ullah ◽  
Tanzil Ur Rahman ◽  
Yi Cheng ◽  
Hai-Yan Pang ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Luciferase Reporter ◽  
Uterine Receptivity ◽  
Positive Role ◽  
Endometrial Cells ◽  
Estrogenic Effects ◽  
Reporter Assays ◽  
Downstream Analysis

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

4-Hydroxyestradiol improves mouse embryo quality, epidermal growth factor-binding capability in vitro and implantation rates

2020 ◽  
Author(s):  
Nuria Hernández ◽  
Marta López-Morató ◽  
Mario J Perianes ◽  
Soledad Sánchez-Mateos ◽  
Vanessa Casas-Rua ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Embryo Quality ◽  
Culture Media ◽  
Embryo Implantation ◽  
In Vivo Models ◽  
Endometrial Cells ◽  
Epidermal Growth ◽  
Binding Capability

Abstract Embryo implantation in the uterus is a critical step to achieve success following ART. Despite favorable uterine conditions, a great number of good quality embryos fail to implant, often for reasons that are unknown. Hence, improving the implantation potential of embryos is a subject of great interest. 4-Hydroxyestradiol (4-OH-E2), a metabolic product of estradiol produced by endometrial cells, plays a key role in endometrial–embryonic interactions that are necessary for implantation. Nonetheless, the effects of 4-OH-E2 on embryos obtained in vitro have not been yet described. This study was designed to determine whether culture media enriched in 4-OH-E2 could improve the quality and implantation rate of embryos obtained in vitro, using both in vitro and in vivo models. We also analyzed its effects on the epidermal growth factor (EGF)-binding capability of the embryos. Our results showed that the presence of 4-OH-E2 in the culture media of embryos during the morula to blastocyst transition increases embryo quality and attachment to endometrial cells in vitro. 4-OH-E2 can also improve viable pregnancy rates of mouse embryos produced in vitro, reaching success rates that are similar to those from embryos obtained directly from the uterus. 4-OH-E2 improved the embryos’ ability to bind EGF, which could be responsible for the increased embryo implantation potential observed. Therefore, our results strongly suggest that 4-OH-E2 is a strong candidate molecule to supplement human IVF culture media in order to improve embryo implantation. However, further research is required before these findings can be translated with efficacy and safety to fertility clinics.

Human chorionic gonadotropin improves endometrial receptivity by increasing the expression of homeobox A10

2020 ◽  
Vol 26 (6) ◽  
pp. 413-424
Author(s):  
Mengchen Zhu ◽  
Shanling Yi ◽  
Xiaomin Huang ◽  
Junan Meng ◽  
Haixiang Sun ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Embryo Implantation ◽  
Endometrial Receptivity ◽  
Endometrial Stromal Cells ◽  
Healthy Control ◽  
Hcg Receptor ◽  
Methyltransferase 1

Abstract Homeobox A10 (HOXA10) is a characterized marker of endometrial receptivity. The mechanism by which hCG intrauterine infusion promotes embryo implantation is still unclear. This study seeks to investigate whether hCG improves endometrial receptivity by increasing expression of HOXA10. HOXA10 expression with human chorionic gonadotropin stimulation was analyzed in vitro and in vivo. Our results demonstrate that HOXA10 was decreased in the endometria of recurrent implantation failure patients compared to that in the healthy control fertile group, also we observed that hCG intrauterine infusion increased endometrial HOXA10 expression. HOXA10, blastocyst-like spheroid expansion area was increased, whereas DNA (cytosine-5-)-methyltransferase 1 was decreased when human endometrial stromal cells (hESCs) were treated with 0.2 IU/ml of hCG for 48 h. HOXA10 promoter methylation was also reduced after hCG treatment. Collagen XV (ColXV) can repress the expression of DNA (cytosine-5-)-methyltransferase 1, and hCG treatment increased the expression of ColXV. However, when the hESCs were treated with LH/hCG receptor small interfering RNA to knock down LH/hCG receptor, hCG treatment failed to repress DNA (cytosine-5-)-methyltransferase 1 expression or to increase ColXV expression. Our findings suggest that hCG may promote embryo implantation by increasing the expression of HOXA10.

Stathmin 1 plays a role in endometrial decidualisation by regulating hypoxia inducible factor-1α and vascular endothelial growth factor during embryo implantation

2017 ◽  
Vol 29 (8) ◽  
pp. 1530 ◽  
Author(s):  
Jinhai Gou ◽  
Jia Jia ◽  
Juntao Feng ◽  
Xia Zhao ◽  
Tao Yi ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Embryo Implantation ◽  
Hypoxia Inducible Factor ◽  
Implantation Site ◽  
Vascular Endothelial ◽  
Stathmin 1 ◽  
Endothelial Growth Factor

The aim of the present study was to explore the potential mechanism underlying stathmin 1 (Stmn1) regulation of embryo implantation, as a continuation of previous proteomic research. Adult healthy female mice were mated naturally with fertile males. Murine uterine tissue was collected during the peri-implantation period. Local expression of Stmn1 during embryo implantation was detected by immunohistochemistry (IHC), which showed that Stmn1 was extensively expressed in endometrial glandular epithelium, vascular endothelium, luminal epithelium and the underlying stromal cells at the implantation site on Day 5. The role of Stmn1 during embryo implantation was evaluated by transient knockdown of Stmn1 in vivo using short interference (si) RNA, and some associated factors including Akt, phosphorylated (p-) Akt, hypoxia-inducible factor (HIF)-1α, prolactin (PRL), insulin-like growth factor binding protein (IGFBP) 1 and vascular endothelial growth factor (VEGF) were examined by western blotting analysis and ELISA. The number of embryos implanted after Stmn1-siRNA infusion into the lumen of one uterine horn was lower than that with normal pregnancies (2.2 ± 1.5 vs 8.6 ± 0.5 respectively; P < 0.05). The expression of VEGF, HIF-1α, p-Akt and the decidualisation biomarkers PRL and IGFBP 1 was upregulated at the implantation site on Day 5, but downregulated after Stmn1-siRNA infusion. These findings suggest that during embryo implantation, knockdown of Stmn1 suppresses decidualisation by inhibiting the expression of p-Akt, HIF-1α and VEGF, thus leading to impaired embryo implantation. These findings provide clues for understanding the complicated process of embryo implantation and the potential role of Stmn1 during 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.

scholarly journals Spatiotemporal expression pattern of progranulin in embryo implantation and placenta formation suggests a role in cell proliferation, remodeling, and angiogenesis

Reproduction ◽  
2008 ◽  
Vol 136 (2) ◽  
pp. 247-257 ◽  
Author(s):  
Joëlle A Desmarais ◽  
Mingju Cao ◽  
Andrew Bateman ◽  
Bruce D Murphy
Keyword(s):  
Cell Proliferation ◽  
Embryo Implantation ◽  
Comparative Sequence Analysis ◽  
Placental Development ◽  
Endometrial Cells ◽  
Sequence Identity ◽  
Spatiotemporal Expression ◽  
Post Implantation

Embryo implantation in the mink is preceded by a variable but obligate period of delay in development. Under the influence of progesterone and unknown luteal factors, the mink embryo implants 11–13 days following its exit from diapause. Recent work suggests that progranulin, a growth factor and secreted glycoprotein, is involved in trophoblast proliferation, placental development and endometrial differentiation in the mouse. Using the mink model of delayed implantation and endotheliochorial placentation, we examined the spatiotemporal distribution of progranulin in trophoblast and endometrium during pre- and early post-implantation gestation in vivo. A partial sequence of the mink progranulin gene was cloned and sequenced. Comparative sequence analysis revealed that exons 1 and 2 of mink progranulin share 86.6, 82.4, and 94.9% of nucleic acid sequence identity with the human, mouse, and dog sequences respectively, and indicated that the invariable residues of the cysteine-rich motifs of progranulin are well conserved in the mink sequence. By in situ hybridization, we show that mink progranulin transcript is present in the cytotrophoblast and in epithelial and stromal endometrial cells at the site of implantation and during early placental formation. Immunohistochemistry revealed the progranulin protein to be strongly expressed in endometrial luminal and glandular epithelium around the time of implantation. In the incipient labyrinth, progranulin expression is localized to cytotrophoblasts and fetal capillaries, as well as to the hypertrophied maternal endothelial cells. This study demonstrates that high levels of progranulin expression correspond to active cell proliferation, remodeling, and angiogenesis occurring during the establishment of the placenta in the mink.

scholarly journals Effects of Endocrine-Disrupting Chemicals on Endometrial Receptivity and Embryo Implantation: A Systematic Review of 34 Mouse Model Studies

2021 ◽  
Vol 18 (13) ◽  
pp. 6840
Author(s):  
Donatella Caserta ◽  
Flavia Costanzi ◽  
Maria Paola De Marco ◽  
Luisa Di Benedetto ◽  
Eleonora Matteucci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mouse Model ◽  
Prolonged Exposure ◽  
Embryo Implantation ◽  
Endocrine Disrupting Chemicals ◽  
Progesterone Receptors ◽  
Endometrial Receptivity ◽  
In Vivo Studies ◽  
Endocrine Disrupting

Several available studies have already analyzed the systemic effects of endocrine-disrupting chemicals (EDCs) on fertile woman and neonatal outcomes, but little is still known in humans about the precise mechanisms of interference of these compounds with the endometrial receptivity. There is consistent evidence that continuous and prolonged exposure to EDCs is a risk factor for reduced fertility and fecundity in women. Preliminary studies on mammalian models provide robust evidence about this issue and could help gynecologists worldwide to prevent long term injury caused by EDCs on human fertility. In this systematic review, we aimed to systematically summarize all available data about EDC effects on blastocyst endometrial implantation. We performed a systematic review using PubMed®/MEDLINE® to summarize all in vivo studies, carried out on mice models, analyzing the molecular consequences of the prolonged exposure of EDC on the implantation process. 34 studies carried out on mouse models were included. Primary effects of EDC were a reduction of the number of implantation sites and pregnancy rates, particularly after BPA and phthalate exposure. Furthermore, the endometrial expression of estrogen (ER) and progesterone receptors (PR), as well as their activation pathways, is compromised after EDC exposure. Finally, the expression of the primary endometrial markers of receptivity (such as MUC1, HOXA10, Inn and E-cadherin) after EDC contact was analyzed. In conclusion EDC deeply affect blastocyst implantation in mouse model. Several players of the implantation mechanism are strongly influenced by the exposure to different categories of EDC.

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