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

PROBLEM: 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. METHOD OF STUDY: 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. RESULTS: 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. CONCLUSIONS: MHC‐I compatibility between the dam and fetus prevented an exacerbated maternal immune response from being mounted against fetal antigens.