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

TL;DR

This study shows that DNA methylation of the IL1R2 gene affects placental development and birth weight in pigs by regulating cell behavior and inflammation.

Contribution

The study reveals a novel epigenetic mechanism linking IL1R2 methylation to placental development and fetal outcomes in pigs.

Findings

HBW placentas show increased IL1R2 methylation and reduced expression.

IL1R2 knockdown promotes PTr2 cell proliferation and reduces apoptosis.

IL1R2 overexpression suppresses cell proliferation and increases apoptosis.

Abstract

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 (IL1R2) 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 IL1R2. Mechanistic studies showed that IL1R2 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 (BAX), caspase-3 (CASP3), and caspase-9 (CASP9). Conversely, IL1R2 overexpression significantly suppressed the proliferation and migration of PTr2 cells, reduced the expression of the proliferation marker proliferating cell nuclear antigen (PCNA), and promoted the expression of the pro-apoptotic gene BAX. Furthermore, IL1R2 knockdown decreased tumor necrosis factor-alpha (TNF-α) production, while overexpression led to opposite results. Collectively, these findings demonstrate that IL1R2 regulates the proliferation, migration, and inflammatory responses of PTr2 cells, thereby modulating the placental development and fetal birth weight.

•HBW placentas exhibit better vasculature with IL1R2 hypermethylation and low expression•IL1R2 knockdown promotes proliferation and inhibits apoptosis in PTr2 cells•IL1R2 overexpression suppresses proliferation and promotes apoptosis in PTr2 cells•IL1R2 acts as a positive regulator of TNF-α in placental inflammation

HBW placentas exhibit better vasculature with IL1R2 hypermethylation and low expression

IL1R2 knockdown promotes proliferation and inhibits apoptosis in PTr2 cells

IL1R2 overexpression suppresses proliferation and promotes apoptosis in PTr2 cells

IL1R2 acts as a positive regulator of TNF-α in placental inflammation

Molecular biology; Epigenetics; Cell biology; Developmental biology

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