MiR-30d在稽留流产胎盘绒毛组织中表达的研究
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摘要
目的通过研究miR-30d在人稽留流产胎盘绒毛组织中的表达模式,探讨miR-30d与稽留流产的关系。方法收集2013年1月至2014年12月于石家庄第六医院治疗的稽留流产患者及同期该院1∶1匹配的正常人工流产孕妇为研究对象,分别为稽留流产组(80例)和对照组(80例);将稽留流产组按照年龄不同分为4个亚组:年龄≤25岁组(Y≤25)、26～30岁组(Y 26～30)、31～35岁组(Y 31～35)、≥36岁组(Y≥36)。收集各组绒毛组织,利用qRT-PCR技术和原位杂交技术检测miR-30d在胎盘绒毛组织中的表达及定位。结果两组比较发现miR-30d在稽留流产组绒毛组织中的表达有上调趋势,但尚无显著性差异(P>0.05)。与对照组比较,miR-30d在Y≤25组患者胎盘绒毛组织中表达显著下调(P<0.01),在Y26～30组患者胎盘绒毛组织中表达极显著降低(P<0.01),在Y 31～35组患者胎盘绒毛组织中表达上调(P<0.05),在Y≥36组患者胎盘绒毛组织中表达没有显著变化(P>0.05)。进一步分析发现在Y≤25组中,70%稽留流产患者胎盘绒毛组织中miR-30d表达显著下调(P<0.01);在Y 26～30组,100%稽留流产患者胎盘绒毛组织中miR-30d表达显著下调(P<0.01);而在Y 31～35组和Y≥36组,miR-30d的表达没有明显规律。原位杂交结果显示miR-30d表达主要定位于胎盘绒毛合体滋养层细胞。结论对于小于30岁的稽留流产患者,miR-30d在胎盘合体滋养层中表达下调,可能是引起稽留流产的原因之一。
Objective: To investigate the relationship between miR-30 d and missed abortion by analyzing expression patterns of miR-30 din placenta tissue of human missed abortion.Methods:The patients with missed abortion treated in the Sixth Hospital of Shijiazhuang from January 2013 to December 2014 were as missed abortion group(n=80)and the normal abortion pregnant women with 1∶1 matching in the same period as the control group(n=80).The missed abortion group was subdivided into four subgroups according to age:≤25 years group,26-30 years group,31-35 years group,and≥36 years group.The expression pattern of miR-30 din placenta tissue was analyzed by qRTPCR,and the location of miR-30 dwas detected by using in-situ hybridization.Results:The expression of miR-30 din the villus tissues of the missed abortion group was upregulated,but there was no significant difference(P >0.05).Compared with the control group,theexpression of miR-30 dwas significantly down-regulated in placental tissues of patients with≤25 years old(P<0.01);the expression in patients with 26-30 years group was significantly decreased(P<0.01);the expression was up-regulated in the patients with 31-35 years group(P<0.05);and there was no significant change in the patients with≥36 years group(P>0.05).Further analysis showed that the expression of miR-30 dwas significantly down-regulated in 70% of missed abortion patients with ≤25 years group and100% of 26-30 years group(P<0.01),and the expression of miR-30 dhad no obvious pattern in the 31-35 years group and≥36 years group.The results of in situ hybridization showed that the positive signals of miR-30 dwere mainly located in syncytrophoblasts.Conclusions:These results suggest that the reduction of miR-30 dexpression may be closely related to the occurrence of missed abortion.
Objective: To investigate the relationship between miR-30 d and missed abortion by analyzing expression patterns of miR-30 din placenta tissue of human missed abortion.Methods:The patients with missed abortion treated in the Sixth Hospital of Shijiazhuang from January 2013 to December 2014 were as missed abortion group(n=80)and the normal abortion pregnant women with 1∶1 matching in the same period as the control group(n=80).The missed abortion group was subdivided into four subgroups according to age:≤25 years group,26-30 years group,31-35 years group,and≥36 years group.The expression pattern of miR-30 din placenta tissue was analyzed by qRTPCR,and the location of miR-30 dwas detected by using in-situ hybridization.Results:The expression of miR-30 din the villus tissues of the missed abortion group was upregulated,but there was no significant difference(P >0.05).Compared with the control group,theexpression of miR-30 dwas significantly down-regulated in placental tissues of patients with≤25 years old(P<0.01);the expression in patients with 26-30 years group was significantly decreased(P<0.01);the expression was up-regulated in the patients with 31-35 years group(P<0.05);and there was no significant change in the patients with≥36 years group(P>0.05).Further analysis showed that the expression of miR-30 dwas significantly down-regulated in 70% of missed abortion patients with ≤25 years group and100% of 26-30 years group(P<0.01),and the expression of miR-30 dhad no obvious pattern in the 31-35 years group and≥36 years group.The results of in situ hybridization showed that the positive signals of miR-30 dwere mainly located in syncytrophoblasts.Conclusions:These results suggest that the reduction of miR-30 dexpression may be closely related to the occurrence of missed abortion.
引文
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[7]张艺玮,郝亚楠,潘晓伟.稽留流产发病因素临床分析[J].河北医药,2018,40:413-415.
[8]Zhu B,Ju S,Chu H,et al.The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma[J].Oncol Lett,2018,15:6094-6106.
[9]Lee J,Park H,Eom J,et al.MicroRNA-mediated regulation of the development and functions of follicular helper T cells[J].Immune Netw,2018,18:e7.
[10]Cai JL,Liu LL,Hu Y,et al.Polychlorinated biphenyls impair endometrial receptivity in vitro via regulating mir-30d expression and epithelial mesenchymal transition[J].Toxicology,2016,365:25-34.
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[12]Ye C,Yu X,Liu X,et al.miR-30dinhibits cell biological progression of Ewing’s sarcoma by suppressing the MEK/ERK and PI3K/Akt pathways in vitro[J].Oncol Lett,2018,15:4390-4396.
[13]Xia HF,Jin XH,Cao ZF,et al.MicroRNA expression and regulation in the uterus during embryo implantation in rat[J].FEBS J,2014,281:1872-1891.
[14]Vilella F,Moreno-Moya JM,Balaguer N,et al.Hsa-miR-30d,secreted by the human endometrium,is taken up by the preimplantation embryo and might modify its transcriptome[J].Development,2015,142:3210-3221.
[15]Xia S,Zhen Y,Ma H,et al.Abnormal expression of microRNA-575leads to missed abortion through regulating apoptosis and angiogenesis[J].Exp Ther Med,2017,14:3993-4000.
[16]植枝福,杨文梅,周卓琳,等.miR-518b在稽留流产患者绒毛组织及血清中的表达及其意义[J].广西医科大学学报,35:328-330.
[17]Ohashi K,Natori S,Kubo T.Change in the mode of gene expression of the hypopharyngeal gland cells with an agedependent role change of the worker honeybee Apis mellifera L[J].Eur J Biochem,1997,249:797-802.
[18]张英晨,叶钢.妊娠中滋养细胞融合的研究进展[J].现代妇产科进展,2006,15:709-711.
[19]Castellucci M,Scheper M,Scheffen I,et al.The development of the human placental villous tree[J].Anat Embryol(Berl),1990,181:117-128.
[20]Huppertz B.The critical role of abnormal trophoblast development in the etiology of preeclampsia[J].Curr Pharm Biotechnol,2018Apr 26,doi:10.2174/138920101966618042 7110547.
[21]Clarke FM,Wilson S,McCarthy R,et al.Early pregnancy factor:large scale isolation of rosette inhibition test-active polypetides from ovine placental extracts[J].J Reprod Immunol,1987,10:133-156.
[22]Jiang K,Wong L,Chen Y,et al.Soluble inflammatory mediators induce transcriptional re-organization that is independent of dna methylation changes in cultured human chorionic villous trophoblasts[J].J Reprod Immunol,2018,128:2-8.
[2]覃花婵.稽留流产发生率增加原因分析[J].吉林医学,2014,35:1952-1953.
[3]Fang Y,Kong B,Yang Q,et al.The p53-HDM2gene-gene polymorphism interaction is associated with the development of missed abortion[J].Hum Reprod,2011,26:1252-1258.
[4]Hwang JH,Kim JW,Hwang JY,et al.Coxsackievirus Binfection is highly related with missed abortion in Korea[J].Yonsei Med J,2014,55:1562-1567.
[5]Keskin F,Karatas A,Albayrak M,et al.Maternal serum soluble HLA-G levels in missed abortions[J].Medicina(Kaunas),2013,49:435-438.
[6]Nielsen S,Hahlin M,Platz-Christensen JJ.Unsuccessful treatment of missed abortion with a combination of an antiprogesterone and a prostaglandin E1analogue[J].Br JObstet Gynaecol,1997,104:1094-1096.
[7]张艺玮,郝亚楠,潘晓伟.稽留流产发病因素临床分析[J].河北医药,2018,40:413-415.
[8]Zhu B,Ju S,Chu H,et al.The potential function of microRNAs as biomarkers and therapeutic targets in multiple myeloma[J].Oncol Lett,2018,15:6094-6106.
[9]Lee J,Park H,Eom J,et al.MicroRNA-mediated regulation of the development and functions of follicular helper T cells[J].Immune Netw,2018,18:e7.
[10]Cai JL,Liu LL,Hu Y,et al.Polychlorinated biphenyls impair endometrial receptivity in vitro via regulating mir-30d expression and epithelial mesenchymal transition[J].Toxicology,2016,365:25-34.
[11]Ozcan S.MiR-30family and EMT in human fetal pancreatic islets[J].Islets,2009,1:283-285.
[12]Ye C,Yu X,Liu X,et al.miR-30dinhibits cell biological progression of Ewing’s sarcoma by suppressing the MEK/ERK and PI3K/Akt pathways in vitro[J].Oncol Lett,2018,15:4390-4396.
[13]Xia HF,Jin XH,Cao ZF,et al.MicroRNA expression and regulation in the uterus during embryo implantation in rat[J].FEBS J,2014,281:1872-1891.
[14]Vilella F,Moreno-Moya JM,Balaguer N,et al.Hsa-miR-30d,secreted by the human endometrium,is taken up by the preimplantation embryo and might modify its transcriptome[J].Development,2015,142:3210-3221.
[15]Xia S,Zhen Y,Ma H,et al.Abnormal expression of microRNA-575leads to missed abortion through regulating apoptosis and angiogenesis[J].Exp Ther Med,2017,14:3993-4000.
[16]植枝福,杨文梅,周卓琳,等.miR-518b在稽留流产患者绒毛组织及血清中的表达及其意义[J].广西医科大学学报,35:328-330.
[17]Ohashi K,Natori S,Kubo T.Change in the mode of gene expression of the hypopharyngeal gland cells with an agedependent role change of the worker honeybee Apis mellifera L[J].Eur J Biochem,1997,249:797-802.
[18]张英晨,叶钢.妊娠中滋养细胞融合的研究进展[J].现代妇产科进展,2006,15:709-711.
[19]Castellucci M,Scheper M,Scheffen I,et al.The development of the human placental villous tree[J].Anat Embryol(Berl),1990,181:117-128.
[20]Huppertz B.The critical role of abnormal trophoblast development in the etiology of preeclampsia[J].Curr Pharm Biotechnol,2018Apr 26,doi:10.2174/138920101966618042 7110547.
[21]Clarke FM,Wilson S,McCarthy R,et al.Early pregnancy factor:large scale isolation of rosette inhibition test-active polypetides from ovine placental extracts[J].J Reprod Immunol,1987,10:133-156.
[22]Jiang K,Wong L,Chen Y,et al.Soluble inflammatory mediators induce transcriptional re-organization that is independent of dna methylation changes in cultured human chorionic villous trophoblasts[J].J Reprod Immunol,2018,128:2-8.