Increased expression of pro-inflammatory cytokines at the fetal-maternal interface in bovine pregnancies produced by cloning.

Increased expression of pro-inflammatory cytokines at the fetal-maternal interface in bovine pregnancies produced by cloning.
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克隆产生的牛妊娠胎儿界面上促炎性细胞因子的表达增加。

DOI:
10.1111/aji.13520
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发表时间:
2022-03
期刊:
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子:
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其他
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在体细胞核移植(SCNT)产生的牛妊娠中观察到明显的自然流产率。主要组织相容性复合物I类(MHC-I)蛋白在SCNT孕体滋养层细胞表面异常表达。通过SCNT确定MHC-I纯合相容(n = 9)、纯合不相容(n = 8)和杂合不相容(n = 5)妊娠。通过人工授精建立了8例对照妊娠。在妊娠第35 ±1天采集子宫和滋养层样本,通过qPCR检测免疫相关基因的表达,并通过测序评估滋养层microRNA的表达。与对照组相比,来自MHC-I杂合子不相容妊娠的滋养层表达CD 28、CTLA 4、CXCL 8、IFNG、IL 1A、IL 2、IL 10、IL 12 B、TBX 21和TNF水平升高,而GNLY表达下调。与对照组相比,MHC-I纯合不相容处理组表达增加的IFNG、IL 1A和IL 2水平,而MHC-I纯合相容组没有差异表达任何基因。在子宫内膜中,相对于对照组,MHC-I杂合子不相容妊娠表达的CD 28、CTLA 4、CXCL 8、IFNG、IL 10、IL 12 B和TNF水平升高,而GATA 3表达下调。与对照组相比,MHC-I纯合子不相容组表达的CSF 2转录物数量减少,但没有任何其他免疫相关基因的异常表达。与对照组相比,MHC-I不相容的妊娠有40个失调的miRNA,与MHC-I相容的妊娠相比,有62个失调的microRNA。母体和胎儿之间的MHC-I相容性可防止针对胎儿抗原的母体免疫应答加剧。
A significant rate of spontaneous abortion is observed in cattle pregnancies produced by somatic cell nuclear transfer (SCNT). Major histocompatibility complex class I (MHC‐I) proteins are abnormally expressed on the surface of trophoblast cells from SCNT conceptuses. MHC‐I homozygous compatible (n = 9), homozygous incompatible (n = 8), and heterozygous incompatible (n = 5) pregnancies were established by SCNT. Eight control pregnancies were established by artificial insemination. Uterine and trophoblast samples were collected on day 35 ±1 of pregnancy, the expression of immune‐related genes was examined by qPCR, and the expression of trophoblast microRNAs was assessed by sequencing. Compared to the control group, trophoblast from MHC‐I heterozygous incompatible pregnancies expressed increased levels of CD28, CTLA4, CXCL8, IFNG, IL1A, IL2, IL10, IL12B, TBX21, and TNF, while GNLY expression was downregulated. The MHC‐I homozygous incompatible treatment group expressed increased levels of IFNG, IL1A, and IL2 while the MHC‐I homozygous compatible group did not differentially express any genes compared to the control group. In the endometrium, relative to the control group, MHC‐I heterozygous incompatible pregnancies expressed increased levels of CD28, CTLA4, CXCL8, IFNG, IL10, IL12B, and TNF, while GATA3 expression was downregulated. The MHC‐I homozygous incompatible group expressed decreased amounts of CSF2 transcripts compared with the control group but did not have abnormal expression of any other immune‐related genes. MHC‐I incompatible pregnancies had 40 deregulated miRNAs compared to control pregnancies and 62 deregulated microRNAs compared to MHC‐I compatible pregnancies. MHC‐I compatibility between the dam and fetus prevented an exacerbated maternal immune response from being mounted against fetal antigens.
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