Suppression of Non-Random Fertilization by MHC Class I Antigens

Int J Mol Sci. 2020 Nov 19;21(22):8731. doi: 10.3390/ijms21228731.

Abstract

Hermaphroditic invertebrates and plants have a self-recognition system on the cell surface of sperm and eggs, which prevents their self-fusion and enhances non-self-fusion, thereby contributing to genetic variation. However, the system of sperm-egg recognition in mammals is under debate. To address this issue, we explored the role of major histocompatibility complex class I (MHC class I, also known as histocompatibility 2-Kb or H2-Kb and H2-Db in mice) antigens by analyzing H2-Kb-/-H2-Db-/-β2-microglobulin (β2M)-/- triple-knockout (T-KO) male mice with full fertility. T-KO sperm exhibited an increased sperm number in the perivitelline space of wild-type (WT) eggs in vitro. Moreover, T-KO sperm showed multiple fusion with zona pellucida (ZP)-free WT eggs, implying that the ability of polyspermy block for sperm from T-KO males was weakened in WT eggs. When T-KO male mice were intercrossed with WT female mice, the percentage of females in progeny increased. We speculate that WT eggs prefer fusion with T-KO sperm, more specifically X-chromosome-bearing sperm (X sperm), suggesting the presence of preferential (non-random) fertilization in mammals, including humans.

Keywords: MHC class I; non-random fertilization; polyspermy block; sex ratio.

MeSH terms

  • Animals
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • Female
  • Fertility / genetics*
  • Fertilization in Vitro
  • Gene Expression Regulation
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Male
  • Mice
  • Mice, Knockout
  • Ovum / cytology
  • Ovum / metabolism*
  • Sex Ratio*
  • Sperm Count
  • Sperm-Ovum Interactions / genetics*
  • Spermatozoa / cytology
  • Spermatozoa / metabolism*
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology

Substances

  • DNA-Binding Proteins
  • Histocompatibility Antigens Class I
  • beta 2-Microglobulin
  • Pfdn6 protein, mouse