Glycerol-3-phosphate acyltransferase 2 is essential for normal spermatogenesis

Biochem J. 2017 Aug 30;474(18):3093-3107. doi: 10.1042/BCJ20161018.

Abstract

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first and rate-limiting step in the de novo glycerolipid synthesis. The GPAT2 isoform differs from the other isoforms because its expression is restricted to male germ cells and cancer cells. It has been recently reported that GPAT2 expression in mouse testis fluctuates during sexual maturation and that it is regulated by epigenetic mechanisms in combination with vitamin A derivatives. Despite progress made in this field, information about GPAT2 role in the developing male germ cells remains unclear. The aim of the present study was to confirm the hypothesis that GPAT2 is required for the normal physiology of testes and male germ cell maturation. The gene was silenced in vivo by inoculating lentiviral particles carrying the sequence of a short-hairpin RNA targeting Gpat2 mRNA into mouse testis. Histological and gene expression analysis showed impaired spermatogenesis and arrest at the pachytene stage. Defects in reproductive fitness were also observed, and the analysis of apoptosis-related gene expression demonstrated the activation of apoptosis in Gpat2-silenced germ cells. These findings indicate that GPAT2 protein is necessary for the normal development of male gonocytes, and that its absence triggers apoptotic mechanisms, thereby decreasing the number of dividing germ cells.

Keywords: GPAT2; apoptosis; gene silencing; germ cell; meiosis; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Glycerol-3-Phosphate O-Acyltransferase / antagonists & inhibitors
  • Glycerol-3-Phosphate O-Acyltransferase / genetics
  • Glycerol-3-Phosphate O-Acyltransferase / metabolism*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence
  • Pachytene Stage
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Seminiferous Tubules / cytology
  • Seminiferous Tubules / growth & development
  • Seminiferous Tubules / metabolism*
  • Spermatogenesis*
  • Spermatozoa / cytology
  • Spermatozoa / enzymology*
  • Spermatozoa / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Proteins
  • Green Fluorescent Proteins
  • Glycerol-3-Phosphate O-Acyltransferase
  • glycerol-3-phosphate acyltransferase 2, mouse