The effect of lysophosphatidic acid-supplemented culture medium on human immature oocytes matured in vitro

Reprod Biol Endocrinol. 2021 Jun 4;19(1):83. doi: 10.1186/s12958-021-00771-8.

Abstract

Background: Lysophosphatidic acid-supplemented culture medium significantly increases the oocyte maturation rate in vitro. However, potential targets and pathways involved remain unknown.

Methods: A total of 43 women, who underwent cesarean section and aged between 18 and 35 years with good health, were included in this study. Immature oocytes were obtained and cultured with 10 µM lysophosphatidic acid. After culture, oocyte maturation was assessed and oocytes and cumulus cells were collected for RNA sequencing. Hierarchical indexing for spliced alignment of transcripts 2 method was used to align clean reads to the human genome. The featureCounts and edgeR package were used to calculate gene expression and analyze differences between groups respectively. ClusterProfiler program was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis.

Results: Oocyte maturation rate increased significantly following 48 h culture with lysophosphatidic acid. In cumulus cells, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in TNF signaling and insulin secretion pathways and downregulated genes were enriched in TNF signaling and cell adhesion molecules. In oocytes, Gene Ontology analysis revealed the top 20 items enriched by upregulated genes and downregulated genes respectively; Kyoto Encyclopedia of Genes and Genomes analysis showed that upregulated genes in the treatment group were enriched in MAPK signaling, gap junction, and cell cycle pathways and downregulated genes were enriched in MAPK signaling, estrogen signaling, RAP1 signaling, and gap junction pathways.

Conclusions: Lysophosphatidic acid in culture medium enhances human oocyte maturation in vitro and the identified some potential pathways may associate with oocyte maturation.

Keywords: Cumulus cells; Fertility; In vitro maturation; Lysophosphatidic acid; Oocytes.

MeSH terms

  • Adult
  • Cell Cycle / genetics
  • Culture Media*
  • Cumulus Cells
  • Down-Regulation
  • Epidermal Growth Factor
  • Estrogens / genetics
  • Estrogens / metabolism
  • Female
  • Follicle Stimulating Hormone
  • Gap Junctions / genetics
  • Gap Junctions / metabolism
  • Gene Expression / drug effects
  • Gene Ontology
  • Humans
  • In Vitro Oocyte Maturation Techniques / methods*
  • Luteinizing Hormone
  • Lysophospholipids / pharmacology*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Oocytes / drug effects*
  • Oocytes / metabolism
  • Ovarian Follicle
  • Signal Transduction
  • Up-Regulation
  • Young Adult

Substances

  • Culture Media
  • Estrogens
  • Lysophospholipids
  • Epidermal Growth Factor
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Mitogen-Activated Protein Kinases
  • lysophosphatidic acid