DNA methylation of the IL1R2 gene is associated with porcine placental development and birth weight

Birth weight, which critically impacts fetal survival, is largely determined by placental development. This study investigated the epigenetic regulation of the interleukin-1 receptor type 2 (<i>IL1R2</i>) gene in regulating placental development and fetal birth weight. The results showed that placentas from piglets with higher birth weight (HBW) exhibited increased DNA methylation and decreased expression of <i>IL1R2</i>. Mechanistic studies showed that <i>IL1R2</i> knockdown promoted the proliferation and migration of porcine trophoblast 2 (PTr2) cells, while downregulating the expression of apoptosis-related genes, including BCL2-associated X protein (<i>BAX</i>), caspase-3 (<i>CASP3</i>), and caspase-9 (<i>CASP9</i>). Conversely, <i>IL1R2</i> overexpression significantly suppressed the proliferation and migration of PTr2 cells, reduced the expression of the proliferation marker proliferating cell nuclear antigen (<i>PCNA</i>), and promoted the expression of the pro-apoptotic gene <i>BAX</i>. Furthermore, IL1R2 knockdown decreased tumor necrosis factor-alpha (TNF-<i>α</i>) production, while overexpression led to opposite results. Collectively, these findings demonstrate that <i>IL1R2</i> regulates the proliferation, migration, and inflammatory responses of PTr2 cells, thereby modulating the placental development and fetal birth weight.