Gene dysregulation impairs placental angiogenesis in allogeneic pig pregnancies.

Embryo transfer (ET) is a valuable reproductive technology in pigs, albeit its efficiency remains significantly lower than that of natural mating or artificial insemination (AI), owing to high embryonic death rates. Critical for embryo survival and pregnancy success is the placenta, which supports conceptus development through nutrient exchange, hormone production, and immune modulation. Alterations in placental development and function may therefore underlie the reduced efficiency of ET. To investigate the molecular mechanisms underlying this dysfunction, crossbred (Landrace × Large White) recipient sows were hormonally synchronized and either inseminated on the onset of estrus (Day 0), (Control group; n = 8) or surgically transferred 23 morulae on Day 5 post-estrus (Allogeneic group; n = 8). Placental samples were collected from four sows per group on Day 18 (attachment phase) and Day 24 (early placentation) of pregnancy. Libraries were prepared using the TruSeq Stranded mRNA kit (Illumina). Sequencing was performed on a NextSeq 550 platform (2 ×75 bp paired-end), and reads were aligned to the Sus scrofa 11.1 genome. Differential gene expression analysis (FC>2/<-2, P < 0.05) revealed significant downregulation of key angiogenic and immune-regulatory genes in allogeneic placentas. On Day 18, VEGFA, NOS3, FGF9, HIF1A, STAT1, STAT3, SMAD1, SMAD4, SMAD5, and ETS1 were markedly reduced, indicating impaired vascular remodeling and immune modulation. By Day 24, SMAD2 and additional immune-related genes remained dysregulated. Conversely, ANGPTL2 was upregulated on Day 24, possibly due to a compensatory angiogenic response. The data suggest that full allogeneicity disrupts placental transcriptomic programs crucial for angiogenesis and immune tolerance, contributing to the high embryonic mortality observed after ET in swine.