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The mechanism underlying the potential risk associated with in vitro fertilization and embryo transfer (IVF-ET) has been previously investigated but remains to be fully elucidated. As the placenta is a critical organ that sustains and protects the fetus, this is an important area of research. The aim of the present study was to determine the difference in trophoblast cell function in the first trimester between naturally conceived pregnancies and pregnancies achieved via IVF-ET therapy. A total of 20 placental villi in first trimester samples were obtained through fetal bud aspiration from patients undergoing IVF-ET due to oviductal factors between January 2016 and August 2018. In addition, a further 20 placental villi were obtained from those who naturally conceived and had normal pregnancies but were undergoing artificial abortion; these patients were recruited as the controls. Reverse transcription-quantitative (RT-q)PCR and semi-quantitative immunohistochemical methods were used to detect the mRNA and protein expression of α-fetoprotein (AFP), vascular endothelial growth factor (VEGF), transferrin (TF), tubulin β1 class VI (TUBB1), metallothionein 1G (MT1G), BCL2, glial cells missing transcription factor 1 (GCM1), epidermal growth factor (EGF) receptor (EGFR), PTEN and leukocyte associated immunoglobulin like receptor 2 (LAIR2) in villi from both groups. Differentially expressed genes were analyzed using Search Tool for the Retrieval of Interacting Genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted. The RT-qPCR data revealed that the mRNA expression levels of AFP, VEGF and TF were significantly higher in the IVF-ET group than in the control group (P<0.05), and those of TUBB1, MT1G, BCL2, GCM1, EGFR, PTEN and LAIR2 were significantly lower (P<0.05). These gene products were expressed in the placental villus tissues, either in the cytoplasm, or in the membrane of syncytiotrophoblast and cytotrophoblast cells. The immunohistochemistry results were in line with those observed using RT-qPCR. KEGG pathway analysis indicated that the trophoblast cell function of the IVF-ET group in the first trimester was different from naturally conceived pregnancies with regard to proliferation, invasion, apoptosis and vascular development. The IVF-ET process may trigger adaptive placental responses, and these compensatory mechanisms could be a risk for certain diseases later in life. [ABSTRACT FROM AUTHOR]