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The Effect of Increased miR-16-1 Levels in Mouse Embryos on Epigenetic Modification, Target Gene Expression, and

Maryam Kiani1, Mohammad Salehi2,3, Asghar Mogheiseh4

  • 1Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

Reproductive Sciences (Thousand Oaks, Calif.)
|July 1, 2020
PubMed

Insights

Increased microRNA-16-1 (miR-16-1) in sperm negatively impacts embryo development and epigenetic markers. This study reveals miR-16-1 affects key gene expressions, offering insights into male infertility causes.

Area of Science:

  • Reproductive Biology and Genetics
  • Epigenetics and Gene Expression
  • Infertility Research

Background:

  • MicroRNA (miRNA) dysregulation is linked to various diseases, including male infertility.
  • The specific impact of elevated miR-16-1 in sperm from infertile men on early embryo development remains largely unknown.

Purpose of the Study:

  • To investigate the effects of increased miR-16-1 expression on human in vitro fertilization (IVF) embryo development.
  • To analyze the impact on crucial epigenetic modifications, specifically histone methylation.
  • To examine the expression patterns of target genes involved in apoptosis and epigenetic regulation.

Main Methods:

  • IVF embryos were microinjected with a miR-16-1 harboring plasmid.
  • Embryo developmental rates were monitored over 96 hours.
  • Immunofluorescence staining assessed histone H3 lysine 4 tri-methylation (H3K4me3) and H3K27me3 levels; quantitative real-time PCR (qRT-PCR) measured gene expression.

Main Results:

  • Microinjection of miR-16-1 significantly impaired embryo development from the 8-cell to blastocyst stage.
  • Reduced levels of H3K4me3 and H3K27me3 were observed in both 2-cell and blastocyst stages.
  • miR-16-1 injection led to increased Bax expression and decreased expression of Bcl-2, Suz12, and Kmt2a.

Conclusions:

  • Elevated miR-16-1 expression adversely affects IVF embryo development.
  • miR-16-1 influences key epigenetic marks (H3K4me3, H3K27me3) and alters the expression of target genes.
  • These findings suggest miR-16-1 is a critical factor in male infertility, impacting reproductive outcomes through epigenetic and genetic mechanisms.
Keywords:
Embryo developmentEpigenesisInfertilitymiR-16-1

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