title: Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse.
abstract: BACKGROUND
  Primordial germ cells (PGCs) are the embryonic precursors of the sperm and eggs. Environmental or genetic defects that alter PGC development can impair fertility or cause formation of germ cell tumors.
  
  
  RESULTS
  We demonstrate a novel role for cholesterol during germ cell migration in mice. Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures. Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR) resulting in germ cell survival and migration defects. These defects were rescued by co-addition of isoprenoids and cholesterol, but neither compound alone was sufficient. In contrast, loss of the last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers or position in vivo. However embryos that lack these enzymes do not exhibit cholesterol defects at the stage at which PGCs are migrating. This demonstrates that during gestation, the cholesterol required for PGC migration can be supplied maternally.
  
  
  CONCLUSIONS
  In the mouse, cholesterol is required for PGC survival and motility. It may act cell-autonomously by regulating clustering of growth factor receptors within PGCs or non cell-autonomously by controlling release of growth factors required for PGC guidance and survival.
authors.affiliation: Department of Genetics Case Western Reserve University, Cleveland, OH, USA. jiaxi.ding@osumc.edu
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Ding
authors.forename: Dechen
authors.initials: D
authors.lastname: Jiang
authors.forename: Michael
authors.initials: M
authors.lastname: Kurczy
authors.forename: Jennifer
authors.initials: J
authors.lastname: Nalepka
authors.forename: Brian
authors.initials: B
authors.lastname: Dudley
authors.forename: Erin I
authors.initials: EI
authors.lastname: Merkel
authors.forename: Forbes D
authors.initials: FD
authors.lastname: Porter
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Ewing
authors.forename: Nicholas
authors.initials: N
authors.lastname: Winograd
authors.forename: James
authors.initials: J
authors.lastname: Burgess
authors.forename: Kathleen
authors.initials: K
authors.lastname: Molyneaux
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases