Scientists have discovered an unexpected link between uterine dysfunction and a protein abundant in mammals called centromere protein B (CENP-B). In a study published in this month's issue of Genome Research, Andy Choo and colleagues (The Murdoch Institute) show that the female mice lacking CENP-B, although otherwise apparently normal, suffer reproductive failure due to defects in the uterus.
CENP-B first drew attention because it binds specifically to the centromere, a chromosome region essential for proper cell division. When scientists bred mutant mice that lack CENP-B, however, the mice appeared surprisingly normal. To take a closer look, Choo and colleagues have now mutated the protein in three genetically distinct mouse strains and examined the effect across all strains. The mice again appeared generally normal, except the males had somewhat reduced testis weight and the females, reduced uterus weight. However, in one strain the females suffered from near complete reproductive dysfunction, with complications during pregnancy that were fatal to the pups or mother. The other two strains appeared reproductively normal at first, but deteriorated with maturity so that the mice very rarely achieved pregnancy at 9 months - an age when non-mutant mice still actively bear young.
As smaller uteruses do not explain these serious defects, the researchers looked for other potential causes. The mutants, they found, had grossly defective cells within the uterine lining, tissue that helps the uterus receive and support developing embryos. Choo and colleagues speculate CENP-B plays a role in cell divisions that remodel the lining during estrus and pregnancy, although future studies are necessary to explore this hypothesis. More studies are also necessary to see whether there is any connection between female infertility in humans and CENP-B dysfunction.
Contact (author):
K.H. Andy Choo
The Murdoch Institute
Royal Children's Hospital
Parkville 3052
Australia
Email: Choo@cryptic.rch.unimelb.edu.au
Fax: 61-3-9348-1391
Journal
Genome Research