Paternal factors and embryonic development: Role in recurrent pregnancy loss

Andrologia. 2019 Feb;51(1):e13171. doi: 10.1111/and.13171. Epub 2018 Oct 15.

Abstract

The events occurring at the maternal-foetal interface define a successful pregnancy but the current paradigm has shifted towards assessing the contribution of spermatozoa for embryogenesis. Spermatozoa with defective DNA integrity may fertilise the oocyte but affect subsequent embryonic development. The present case-control study was conducted in male partners of couples experiencing recurrent pregnancy loss (RPL) to assess the gene expression of spermatozoal FOXG1, SOX3, OGG1, PARP1, RPS6, RBM9, RPS17 and RPL29. This was correlated with reactive oxygen species (ROS) levels and DNA Fragmentation Index (DFI). Semen samples were obtained from 60 cases and 30 fertile controls. Gene expression was done by qPCR analysis, and relative quantification was calculated by the 2-ΔΔCt method. Chemiluminescence and the sperm chromatin structure assay were used to measure the ROS and DFI levels respectively. FOXG1, OGG1, RPS6 and RBM9 were seen to be upregulated, while SOX3 and PARP1 were downregulated. Relative expression of SOX3, OGG1, RPS6 and RPS17 showed a significant difference between patients and controls (p < 0.05). RPL patients were seen to have high ROS (>27.8; p = 0.001) and DFI (>30.7; p < 0.0001) with respect to controls. Sperm transcript dysregulation and oxidative DNA damage can be "carried over" after implantation, thus affecting embryogenesis and health of the future progeny.

Keywords: DNA damage; embryogenesis; gene expression; oxidative stress; sperm transcripts.

MeSH terms

  • Abortion, Habitual / genetics*
  • Abortion, Habitual / metabolism
  • Adult
  • Case-Control Studies
  • Chromatin / metabolism
  • DNA Fragmentation*
  • Female
  • Gene Expression Regulation
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / metabolism
  • Male
  • Oxidative Stress / genetics
  • Reactive Oxygen Species / metabolism*
  • Sperm Count
  • Spermatozoa / metabolism*

Substances

  • Chromatin
  • Reactive Oxygen Species