Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah, USA.
School of Veterinary Medicine, Utah State University, Logan, Utah, USA.
Am J Reprod Immunol. 2022 Mar;87(3):e13520. doi: 10.1111/aji.13520. Epub 2022 Jan 16.
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.
通过体细胞核移植（SCNT）产生的牛妊娠中，自发性流产的发生率很高。SCNT 胚胎的滋养层细胞表面异常表达主要组织相容性复合体 I 类（MHC-I）蛋白。
通过 SCNT 建立了 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 个对照妊娠。在妊娠第 35±1 天收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，MHC-I 杂合不相容妊娠的滋养层细胞表达 CD28、CTLA4、CXCL8、IFNG、IL1A、IL2、IL10、IL12B、TBX21 和 TNF 的水平增加，而 GNLY 的表达下调。MHC-I 纯合不相容处理组表达 IFNG、IL1A 和 IL2 的水平增加，而 MHC-I 纯合相容组与对照组相比没有差异表达任何基因。在子宫内膜中，与对照组相比，MHC-I 杂合不相容妊娠表达 CD28、CTLA4、CXCL8、IFNG、IL10、IL12B 和 TNF 的水平增加，而 GATA3 的表达下调。与对照组相比，MHC-I 纯合不相容组 CSF2 转录本的表达减少，但其他免疫相关基因没有异常表达。与对照组相比，MHC-I 不相容妊娠有 40 个下调的 miRNA，与 MHC-I 相容妊娠相比有 62 个下调的 microRNA。
母胎之间 MHC-I 的相容性防止了针对胎儿抗原的母体免疫反应加剧。
