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1.
孙永成  王锋  赵雪萍  许丹 《四川动物》2007,26(1):235-238
胚胎移植成功的标志性事件是胚胎着床。着床是一个高度协调的事件,影响胚胎着床的因素主要有胚胎质量和子宫内膜容受性两方面。  相似文献   

2.
胚泡着床窗口的分子调控   总被引:5,自引:0,他引:5       下载免费PDF全文
着床窗口是指当胚胎发育到胚泡阶段时,子宫也增殖和分化到可接受状态,二者相互作用使胚泡着床的短暂时间.雌激素和孕酮是该过程的综合调控分子,它们通过多种局部信号分子的介导,使子宫中的各种细胞类型增殖、分化,为着床窗口的开放做出相互协调的反应.子宫与胚胎在着床窗口通过前列腺素、组织胺、降钙素、多种细胞因子和生长因子的旁分泌作用进行分子对话,使胚泡滋养层与子宫内膜上皮发生附着反应.着床窗口一旦开放,即自动向非接受态转化.  相似文献   

3.
摘要 目的:探讨子宫内膜容受性检测(ERT)技术在反复种植失败患者冻融胚胎移植(FET)中的应用价值,并分析其临床妊娠的影响因素。方法:回顾性分析2019年10月~2022年4月期间海南省妇女儿童医学中心收治的150例反复种植失败患者的临床资料,根据是否接受ERT技术分为ERT组(n=78,接受ERT技术)和无ERT组(n=72,未接受ERT技术)。按照反复种植失败患者是否临床妊娠分为临床妊娠组和未临床妊娠组。采用单因素和多因素Logistic回归模型分析临床妊娠的影响因素。结果:两组异位妊娠率组间对比未见统计学差异(P>0.05)。ERT组临床妊娠率、活产率高于无ERT组,移植日内膜厚度大于无ERT组,移植胚胎数少于无ERT组,流产率低于无ERT组(P<0.05)。所有患者按照是否临床妊娠分为临床妊娠组(n=85)和未临床妊娠组(n=65)。单因素分析结果显示:临床妊娠与年龄、移植胚胎类别、移植胚胎数量、总周期数、FSH、子宫内膜厚度、子宫内膜类型有关(P<0.05),而与体质量指数(BMI)、不孕年限、不孕类型、胚胎冷冻保存时间无关(P>0.05)。多因素Logistic回归分析结果显示:年龄偏大、FSH偏高是临床妊娠的危险因素,而移植胚胎类别为囊胚、移植胚胎数量偏多是临床妊娠的保护因素(P<0.05)。结论:ERT技术用于反复种植失败患者FET中,可有效改善患者的临床妊娠。年龄、FSH、移植胚胎类别、移植胚胎数量是临床妊娠的影响因素。  相似文献   

4.
胚胎植入涉及胚胎与母体子宫内膜间复杂的相互作用,目前对于胚胎植入仍然有许多问题有待探究。子宫内膜上皮类器官与子宫内膜组装体模型为体外研究胚胎植入的过程提供了一个全新的思路。本文总结了胚胎植入过程、雌孕激素协同、胚胎源信号对子宫内膜容受态建立的调控机制、子宫内膜类器官的建立、子宫内膜组装体以及利用内膜组装体探索母-胎互作的最新研究进展,为研究胚胎植入过程中胚胎与母体子宫间的交流互作提供了新策略。  相似文献   

5.
  总被引:15,自引:0,他引:15  
Heparin-binding epidermal growth factor (HB-EGF) is a recently identified member of the EGF growth factor family found to be expressed in the uterus of both mouse and human at the time of implantation. In the present study, we investigated the expression patterns of HB-EGF in normal cycling endometrium and compared its expression with the fertility-associated endometrial epithelial biomarkers alpha(v)beta(3) integrin, leukemia inhibitory factor (LIF) and homeobox gene, HOXA-10. RNase protection assay (RPA) using RNA made from endometrium collected from different phases of the menstrual cycle demonstrated increased HB-EGF expression during the mid-secretory phase, a pattern similar to, but slightly preceding the expression of alpha(v)beta(3) integrin and HOXA-10. In vitro studies demonstrated stimulation of HB-EGF expression by estradiol-17beta (E(2)) and progesterone (P(4)) alone or in combination in stromal cells. Combined treatment with E(2) + P(4) was, however, required to stimulate epithelial HB-EGF expression. In vitro experiments demonstrated the ability of HB-EGF to stimulate epithelial expression of the key endometrial proteins including LIF, HOXA-10, and the beta(3) integrin subunit. Each has previously been demonstrated to be an important epithelial biomarker expressed during the implantation window. In addition, conditioned media from endometrial stromal cells treated with E(2) + P(4) + relaxin mimicked the stimulatory effect of HB-EGF on epithelial expression of the beta(3) integrin subunit. The stimulatory effect of the stromal-conditioned medium was blocked by antibodies that neutralize a known receptor for HB-EGF. These data suggest that uterine receptivity may be regulated in part by the stromal-derived HB-EGF.  相似文献   

6.
目的研究外源性MRP-1/CD9抗体对小鼠胚胎着床的影响。方法1.将8-细胞小鼠胚胎培养于含不同浓度MRP-1/CD9抗体的培养液中,观察囊胚形成及囊胚脱透明带的情况。2.妊娠D4小鼠子宫角注射MRP-1/CD9抗体,于妊娠D8观察小鼠胚胎植入数量。结果1.体外培养时,MRP-1/CD9抗体显著抑制胚胎的囊胚形成率(1:400,P<0.05)和脱带率(1∶800,P<0.05)。2.宫角注射MRP-1/CD9抗体可以显著提高小鼠胚胎的着床数(8.33±0.15vs4.57±0.21)。结论MRP-1/CD9参入小鼠胚胎的发育及植入。  相似文献   

7.
    
It is well known that embryo implantation is a critical process in which embryo should be able to reach and attach to endometrium. Until now, various types of factors are involved in the regulation of this process. S100 proteins are calcium-binding proteins, which have vital roles in embryo implantation and have been considered as possible candidate markers for endometrial receptivity. However, studies regarding mode of actions of these proteins are scarce and more mechanistic insights are needed to clarify exact roles of each one of the S100 protein family. Understanding of function of these proteins in different compartments, stages, and phases of endometrium, could pave the way for conducting studies regarding the therapeutic significance of these proteins in some disorders such as recurrent implantation failure. In this review, we outlined roles and possible underlying mechanisms of S100 protein family in embryo implantation.  相似文献   

8.
    
γ‐Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity–related factors—LIF, E‐cadherin, and HOXA10—were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 μg/μL) markedly inhibited preimplantation embryo development in a dose‐response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 μΜ 2‐hydroxysaclofen, a GABAB antagonist, indicating that GABA exerts its inhibitory effects via its B‐type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B‐type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.  相似文献   

9.
    
Glycosylation alters the molecular and functional features of glycoproteins, which is closely related with many physiological processes and diseases. During “window of implantation”, uterine endometrium transforms into a receptive status to accept the embryo, thereby establishing successful embryo implantation. In this article, we aimed at investigating the role of N-glycosylation, a major modification type of glycoproteins, in the process of endometrial receptivity establishment. Results found that human uterine endometrial tissues at mid-secretory phase exhibited Lectin PHA-E+L (recognizes the branched N-glycans) positive N-glycans as measured by the Lectin fluorescent staining analysis. By utilizing in vitro implantation model, we found that de-N-glycosylation of human endometrial Ishikawa and RL95-2 cells by tunicamycin (inhibitor of N-glycosylation) and peptide-N-glycosidase F (PNGase F) impaired their receptive ability to human trophoblastic JAR cells. Meanwhile, N-glycosylation of integrin αvβ3 and leukemia inhibitory factor receptor (LIFR) are found to play key roles in regulating the ECM-dependent FAK/Paxillin and LIF-induced STAT3 signaling pathways, respectively, thus affecting the receptive potentials of endometrial cells. Furthermore, in vivo experiments and primary mouse endometrial cells-embryos coculture model further verified that N-glycosylation of mouse endometrial cells contributed to the successful implantation. Our results provide new evidence to show that N-glycosylation of uterine endometrium is essential for maintaining the receptive functions, which gives a better understanding of the glycobiology of implantation.  相似文献   

10.
    
In vitro fertilization has overcome infertility issues for many couples. However, achieving implantation of a viable embryo into the maternal endometrium remains a limiting step in optimizing pregnancy success. The molecular mechanisms which characterize the transient state of endometrial receptivity, critical in enabling embryo‐endometrial interactions, and proteins which underpin adhesion at the implantation interface, are limited in humans despite these temporally regulated processes fundamental to life. Hence, failure of implantation remains the “final frontier” in infertility. A human coculture model is utilized utilizing spheroids of a trophectoderm (trophoblast stem) cell line, derived from pre‐implantation human embryos, and primary human endometrial epithelial cells, to functionally identify “fertile” versus “infertile” endometrial epithelium based on adhesion between these cell types. Quantitative proteomics identified proteins associated with human endometrial epithelial receptivity (“epithelial receptome”) and trophectoderm adhesion (“adhesome”). As validation, key “epithelial receptome” proteins (MAGT‐1/CDA/LGMN/KYNU/PC4) localized to the epithelium of receptive phase (mid‐secretory) endometrium obtained from fertile, normally cycling women but is largely absent from non‐receptive (proliferative) phase tissues. Factors involved in embryo‐epithelium interaction in successive temporal stages of endometrial receptivity and implantation are demonstrated and potential targets for improving fertility are provided, enhancing potential to become pregnant either naturally or in a clinical setting.  相似文献   

11.
    
《Reproductive biology》2021,21(4):100569
The successful implantation of the embryo into a receptive endometrium is essential for the establishment of a viable pregnancy while recurrent implantation failure (RIF) is a real challenge in assisted reproduction. The maternal innate immune system, specifically the Toll-like receptors (TLRs), are involved in maintaining immunity in the female reproductive tract (FRT) required for fertility. In this study, we aimed to investigate the importance of innate immunity-related gene expression in the regulation of human fertility and as a prediction of potential outcome of in vitro fertilization - embryo transfer (IVF-ET), thus, we assessed the gene expression levels of TLR signalling molecules using quantitative real-time PCR between endometrial biopsies of healthy fertile women, and the patients experiencing RIF. Interestingly, our results showed that, TRIB2 and TLR9 genes were differentially expressed between the endometrial biopsies of healthy women and those with RIF. However, comparing expression levels of same genes between pre-receptive and receptive healthy endometrial biopsies showed different genes (ICAM1, NFKBIA, VCAM1, LIF, VEGFB, TLR5) had significantly altered expression, suggesting their involvement in endometrial receptivity. Thus, further investigations will enable us to better understand the role of these genes in the biology of FRT and as a possible target for the improvement of infertility treatments and/or development of non-hormonal contraception.  相似文献   

12.
13.
Oviductins are a family of glycoproteins which are synthesized and secreted by oviductal secretory cells and which, upon their secretion in the lumen of the oviduct, become associated with postovulatory oocytes and developing embryos. Recently, we showed that hamster oviductin is maximally secreted in the oviduct at the time of ovulation and is later associated with a certain population of uterine epithelial cells, where it is subsequently endocytosed and degraded. In light of these results, this study was conducted to follow the fate of hamster oviductin in the oviduct and uterus during early gestation. Using a monoclonal antibody against hamster oviductin, immunofluorescence and immunogold labeling revealed that during early gestation, immunoreactivity to oviductin in the uterus gradually diminished to an almost total disappearance at time of implantation. However, the strong labeling intensity remained unchanged in the oviduct. Biochemical analyses demonstrated that a degradation of oviductin occurs in the uterus, and a loss of immunoreactivity was also observed as gestation progressed, so that by the time of implantation, immunoreactivity to oviductin was barely detectable. The decrease of oviductin along the uterine epithelium at the time of blastocyst attachment and its final disappearance at implantation suggest that this glycoprotein could be a potential modulator of uterine receptivity. Mol. Reprod. Dev. 46:306–317, 1997. © 1997 Wiley-Liss, Inc.  相似文献   

14.
    
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15.
目的:观察电针结合红外线照射对反复着床失败(RIF)患者子宫内膜容受性、胚胎移植及妊娠情况的影响。方法:选取102例于2015年5月-2018年5月在我院行复苏胚胎移植的RIF患者,按照随机数字表法将患者分为电针结合红外线照射治疗组(A组,38例)、安慰针刺组(B组,34例)及空白对照组(C组,30例)。比较三组治疗前后血清雌二醇、孕酮水平,于治疗前后检测子宫内膜容受性超声学指标,包括子宫内膜厚度、内膜容积、血管血流指数(VFI)、内膜血流指数(FI)、阻力指数(RI),比较三组胚胎移植及妊娠情况。结果:三组治疗前后血清雌二醇、孕酮水平比较无统计学差异(P0.05)。治疗后A组子宫内膜厚度、内膜容积大于治疗前及B组、C组,VFI、FI高于治疗前及B组、C组,RI低于治疗前及B组、C组(P0.05)。三组移植胚胎数、生化妊娠率、临床妊娠率比较无统计学差异(P0.05),A组胚胎着床率高于B组、C组(P0.05)。结论:电针结合红外线照射治疗RIF患者可以改善子宫内膜容受性,提高胚胎着床率。  相似文献   

16.
    
Insufficient endometrial angiogenesis during peri‐implantation impairs endometrial receptivity (ER), which contributes to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF‐ET). Angiopoietin‐like protein 4 (ANGPTL4) acts as a multifunctional secretory protein and is involved in the regulation of lipid metabolism and angiogenesis in various tissues including the endometrium. Herein, we found decreased ANGPTL4 expression in endometrial tissue and serum during peri‐implantation period in 18 RIF‐affected women with elevated uterine arterial impedance (UAI) compared with the pregnancy controls. ANGPTL4 and peroxisome proliferator‐activated receptor gamma (PPARγ) expression were up‐regulated upon decidualization on human endometrial stromal cells (HESCs). Rosiglitazone promoted the expression of ANGPTL4 in HESCs and human umbilical vein endothelial cells (HUVECs) via PPARγ. ANGPTL4 promoted the proliferation, migration and angiogenesis of HUVECs in vitro. Our results suggest that decreased abundance of ANGPTL4 in endometrial tissues impairs the endometrial receptivity via restraining endometrial angiogenesis during decidualization; while rosiglitazone‐induced ANGPTL4 up‐regulation in hESCs and HUVECs through PPARγ. Therefore, ANGPTL4 could be a potential therapeutic approach for some RIF‐affected women with elevated UAI.  相似文献   

17.
    
Calcitonin (CT) is one of the factors affecting the embryo implantation, but its effects on the implantation window have not been fully investigated. The current study investigated the effects of CT on the endometrium receptivity by morphological study and evaluation of leukemia inhibitory factor (LIF), mucin 1 (Muc-1), and microRNA (miRNA) Let-7a in the ovarian stimulation and the normal ovarian cycle. Then the mechanism of the CT effects through the mammalian target of rapamycin (mTOR) signaling pathway was studied by using PP242. A total of 64 BALB/c mice were divided into the normal ovarian cycle and ovarian stimulation groups. Each group consisted of four subgroups: control, calcitonin, PP242, and calcitonin+PP242. CT and PP242 were injected on the fourth of pregnancy into the mice and 24 hr later all the mice were killed. The uterine tissue samples were used for morphological analysis, and endometrial cells were mechanically isolated for evaluation of gene and protein expression. The results showed that ovarian stimulation induced mTOR phosphorylation as well as increased expression of the Let-7a miRNA. In addition, CT injection increased the expression of LIF and miRNA Let-7a in ovarian stimulation similar to that in normal ovarian cycles. However, injection of PP242 reduced expression of miRNA Let-7a and increased Muc-1 expression in ovarian stimulation group. In conclusion, the administration of CT improved endometrial receptivity in mice. This phenomenon occurred by upregulation of LIF, miRNA Let-7a and downregulation of Muc-1 via mTOR signaling pathway.  相似文献   

18.
    
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19.
    
Understanding the underlying mechanisms by which a normal cell avoids the oncogenic potential of MUC1 signaling requires further definition of the pathways by which the MUC1 cytoplasmic tail is processed in both normal and tumor‐derived cells. In the present study we describe the processing pathway initiated by TACE/ADAM17 cleavage of MUC1. Utilizing the human uterine epithelial cell line, HES, derived from normal endometrium, we show that endogenous full length MUC1 undergoes regulated intramembranous proteolysis mediated by presenillin‐dependent γ‐secretase. Cytokine‐stimulated HES cells exposed to γ‐secretase inhibitors accumulated a membrane‐associated 15 kDa fragment of the MUC1 C‐terminal subunit (CTF15). Inhibitors of TACE/ADAM17‐mediated shedding inhibited accumulation of MUC1‐CTF15 and MUC1 ectodomain release to a similar extent consistent with MUC1‐CTF15 being a product of TACE/ADAM17 action. Reduction of catalytically active γ‐secretase complex by nicastrin siRNA treatment also resulted in CTF15 accumulation. Furthermore, mature nicastrin, the substrate receptor for γ‐secretase, co‐immunoprecipitated with CTF15 in the presence of γ‐secretase inhibitors indicating the formation of CTF15: nicastrin complexes. MUC1‐CTF15 accumulation in response to γ‐secretase inhibition was demonstrated in both normal and tumor‐derived cells from humans and mice indicating that this processing pathway exists in many cell contexts. We did not detect products of MUC1 cleavage by γ‐secretase in the presence of various proteasomal inhibitors indicating that subsequent degradation is either non‐proteasomal or extremely efficient. We suggest that this efficient pathway attenuates potential signaling mediated by cytoplasmic tail fragments. J. Cell. Biochem. 108: 802–815, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

20.
目的

探究行辅助生殖技术(ART)反复着床失败患者应用乳酸菌阴道胶囊辅助治疗对子宫内膜容受性(ER)和阴道微生物的影响。

方法

选取2020年5月至2022年5月本院收治ART反复着床失败患者100例,根据治疗方式分为观察组(n = 50)和对照组(n = 50)。对照组采用常规治疗,观察组采用常规治疗联合乳酸菌阴道胶囊。比较两组的性激素水平(雌二醇、孕酮),内膜容积、子宫内膜厚度、血管血流指数(VFI)、内膜血流指数(FI)和阻力指数(RI)等子宫内膜容受性指标,阴道pH值、阴道菌群检出率和乳酸菌数量。

结果

两组治疗前后血清雌二醇、孕酮水平比较,差异无统计学意义(P>0.05)。两组治疗前子宫内膜厚度、内膜容积、血管血流指数、内膜血流指数和阻力指数比较,差异无统计学意义(P>0.05)。治疗后观察组子宫内膜厚度、内膜容积和血管血流指数均高于治疗前(P<0.01)和对照组(P<0.05)。治疗前两组菌群检出率差异无统计学意义(P>0.05),治疗后两组菌群检出率均低于治疗前(P<0.05),治疗后观察组菌群检出率低于对照组(P<0.05)。两组阴道pH值均低于治疗前(P<0.001),治疗后观察组阴道pH值低于对照组(P<0.001)。两组阴道乳杆菌正常率均高于治疗前(P<0.05),治疗后观察组高于对照组(P<0.05)。两组胚胎着床率、临床妊娠率、早期流产率和持续妊娠率差异无统计学意义(P>0.05)。

结论

乳酸菌阴道胶囊治疗ART反复着床失败患者可以改善子宫内膜容受性和阴道菌群。

  相似文献   

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