Ssc-miR-21-5p regulates endometrial epithelial cell proliferation, apoptosis and migration via the PDCD4/AKT pathway

Renwu Hua1, Xiuling Zhang1, Wenchao Li1

  • 1Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430000, China.

Journal of Cell Science
|October 24, 2020
PubMed

Insights

MicroRNAs regulate gene expression and embryo implantation. This study shows that ssc-miR-21-5p in pigs is crucial for endometrial receptivity by targeting PDCD4 and influencing the AKT pathway, impacting embryo implantation.

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Genetics

Background:

  • Endometrial receptivity is critical for successful embryo implantation.
  • MicroRNAs (miRNAs) are key regulators of gene expression, but their role in early pregnancy is not fully understood.
  • The specific function of miRNAs in porcine endometrial receptivity requires further investigation.

Purpose of the Study:

  • To investigate the role of ssc-miR-21-5p in regulating endometrial receptivity during the pre-implantation period in pigs.
  • To identify the molecular targets and pathways affected by ssc-miR-21-5p in endometrial epithelial cells (EECs).

Main Methods:

  • Quantitative analysis of ssc-miR-21-5p expression in porcine endometrium during pregnancy.
  • In vitro knockdown of ssc-miR-21-5p in porcine EECs to assess effects on cell proliferation, migration, and apoptosis.
  • Verification of programmed cell death 4 (PDCD4) as a direct target of ssc-miR-21-5p.
  • Analysis of the PDCD4/AKT pathway, including AKT1 phosphorylation and downstream targets (Bax, Bcl2, Mmp9).
  • In vivo functional study using mmu-miR-21-5p loss-of-function in mice.

Main Results:

  • ssc-miR-21-5p expression increased significantly in porcine endometrium from day 9 to day 12 of pregnancy.
  • Knockdown of ssc-miR-21-5p inhibited EEC proliferation and migration while inducing apoptosis.
  • PDCD4 was confirmed as a target of ssc-miR-21-5p, and its inhibition rescued the effects of ssc-miR-21-5p repression.
  • ssc-miR-21-5p knockdown impeded AKT1 phosphorylation via PDCD4, leading to increased Bax and decreased Bcl2 and Mmp9 levels.
  • Loss of mmu-miR-21-5p function in vivo reduced the number of implanted mouse embryos.

Conclusions:

  • ssc-miR-21-5p plays a crucial role in regulating endometrial receptivity in pigs.
  • The mechanism involves the modulation of the PDCD4/AKT pathway, affecting cell fate and implantation.
  • These findings provide insights into the molecular regulation of early pregnancy in pigs.

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