The effects of NONRATT008453.2 on autophagy in genital tubercle fibroblasts of rats with hypospadias induced by dibutyl phthalate

Birth Defects Res. 2021 Mar 15;113(5):399-408. doi: 10.1002/bdr2.1863. Epub 2021 Jan 15.

Abstract

Background: Hypospadias is a common birth defect that might be caused by inadequate fusion of the urethral folds in the process of male external genital development. We intended to discover the crucial long noncoding RNAs (lncRNAs) regulating autophagy from the gene expression profile of the genital tubercle (GT) of dibutyl phthalate (DBP) induced hypospadiac rats.

Methods: Whole transcriptome resequencing was used to determine the expression of the total RNA in GTs and cultured fibroblasts obtained from GTs of DBP-induced hypospadiac male rat fetuses. Autophagosomes and autolysosomes were examined under a transmission electron microscope after overexpression of lncRNA NONRATT008453.2 in the fibroblasts by adenovirus transfection. Finally, the protein expression levels of Atg5, Beclin-1, Atg7, and the LC3A/B-II:LC3A/B-I ratio were detected in the fibroblasts by western blotting.

Results: NONRATT008453.2 suppressed autophagy by promoting the expression of Atg7, but inhibited the expressions of Atg5, Beclin-1, and the LC3A/B-II:LC3A/B-I ratio in the GT fibroblasts.

Conclusions: NONRATT008453.2 may have an influence on autophagy in the fibroblasts of the GT in DBP-induced hypospadiac rats.

Keywords: autophagy; dibutyl phthalate; hypospadias; long noncoding RNAs; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Dibutyl Phthalate* / toxicity
  • Female
  • Fibroblasts
  • Humans
  • Hypospadias* / chemically induced
  • Hypospadias* / genetics
  • Male
  • Maternal Exposure
  • Plasticizers
  • Rats
  • Rats, Sprague-Dawley
  • Urethra

Substances

  • Plasticizers
  • Dibutyl Phthalate