Jiaxi Ding¹ , DeChen Jiang² , Michael Kurczy³ , Jennifer Nalepka¹ , Brian Dudley¹ , Erin I Merkel⁴ , Forbes D Porter⁴ , Andrew G Ewing^3,5 , Nicholas Winograd³ , James Burgess²  and Kathleen Molyneaux¹ 

¹Department of Genetics Case Western Reserve University, Cleveland, OH, USA

²Department of Chemistry, Case Western Reserve University, Cleveland, OH, USA

³Department of Chemistry, Penn State University, University Park, PA, USA

⁴Program
on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, MD, USA

⁵Department of Chemistry, Gothenburg University, Kemivägen 4, SE-41296 Gothenburg, Sweden

BMC Developmental Biology 2008,
8:120 [Open Access]

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.

Conclusion

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.