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Abstract <p>Fetal growth retardation (FGR) remains a major cause of perinatal morbidity and mortality, as well as long-term developmental disabilities associated with chronic hypoxia and placental insufficiency. Molecular alterations arising under conditions of oxidative stress, including changes in post-transcriptional regulation of genes responsible for cellular adaptation to DNA damage, are one of the key factors of FGR pathogenesis. In the present study, we have performed a whole transcriptome analysis of alternative splicing events in placental decidual cells during physiological pregnancy and FGR. Data obtained indicate the involvement of DNA repair pathways in the adaptive response of placental tissue to hypoxic stress. The <i>POLB</i> gene was among the genes with significant splicing alterations. This gene encodes DNA polymerase β, a key enzyme of the base excision repair system, which provides the repair of single-strand DNA breaks. For the first time, it has been demonstrated that in the case of FGR, a statistically significant alternative splicing event, manifested by a higher frequency of exon 2 inclusion, is typical for the <i>POLB</i> gene. The splicing index of this exon during FGR was almost three times higher than the values observed in the control group (Δ<i>PSI</i> = 0.484). Under conditions of placental hypoxia, stress-dependent mechanisms of splicing regulation are activated, which can lead to increased inclusion of exon 2 in pre-mRNA of the <i>POLB</i> gene. Data obtained suggest that changes in the <i>POLB</i> gene splicing are a possible adaptive response of placental tissue to hypoxic stress, which is one of the pathogenetic factors during fetal growth retardation.</p>

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The Role of the POLB Gene Alternative Splicing in the Fetal Growth Retardation Pathogenesis

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • M. M. Gavrilenko,
  • E. A. Trifonova,
  • A. A. Babovskaya,
  • E. V. Izhoykina,
  • M. G. Swarovskaja,
  • V. A. Stepanov

摘要

Abstract

Fetal growth retardation (FGR) remains a major cause of perinatal morbidity and mortality, as well as long-term developmental disabilities associated with chronic hypoxia and placental insufficiency. Molecular alterations arising under conditions of oxidative stress, including changes in post-transcriptional regulation of genes responsible for cellular adaptation to DNA damage, are one of the key factors of FGR pathogenesis. In the present study, we have performed a whole transcriptome analysis of alternative splicing events in placental decidual cells during physiological pregnancy and FGR. Data obtained indicate the involvement of DNA repair pathways in the adaptive response of placental tissue to hypoxic stress. The POLB gene was among the genes with significant splicing alterations. This gene encodes DNA polymerase β, a key enzyme of the base excision repair system, which provides the repair of single-strand DNA breaks. For the first time, it has been demonstrated that in the case of FGR, a statistically significant alternative splicing event, manifested by a higher frequency of exon 2 inclusion, is typical for the POLB gene. The splicing index of this exon during FGR was almost three times higher than the values observed in the control group (ΔPSI = 0.484). Under conditions of placental hypoxia, stress-dependent mechanisms of splicing regulation are activated, which can lead to increased inclusion of exon 2 in pre-mRNA of the POLB gene. Data obtained suggest that changes in the POLB gene splicing are a possible adaptive response of placental tissue to hypoxic stress, which is one of the pathogenetic factors during fetal growth retardation.