Single mutation disrupts morphology of sexual organs
11 Nov 2014 by hhwdjwbphm.d hhwdjwbphm.d
A single mutation in a gene coding for a protein deeply involved in developmental and homeostatic processes can lead to infertility not by disrupting gamete production but by causing abnormalities in the morphology of sexual organs.
Researchers at the RIKEN BioResource Center developed a mouse with a single mutation to the beta-catenin gene – an essential part of the Wnt/beta-catenin signalling pathway, which is involved in the development and maintenance of nearly all organs throughout the rodent’s life.
They were hoping to discover so far unfound functions of the gene, which is well conserved through evolution. They created mice with single changes in amino acids, and from testing, found a strain where mice could not reproduced through natural mating, but could through in vitro fertilisation.
This suggests the problem was caused by a structural problem rather than with the eggs or sperm. In these mice, the pathway didn’t shut off properly in certain tissues leading to malformations of the sexual organs – seminal vesicles in males and vaginas in females – that prevented successful reproduction.
"Because the amino acid sequence of beta-catenin is 100% identical in humans and mice, the nucleotide change we saw could cause the same mutation in humans,” said Takuya Murata, first author of the paper published in Scientific Reports.
“This raises the possibility that some infertility could be caused by beta-catenin, which has not generally been considered as a potential cause so far. This finding came as a major surprise because we were expecting to see effects on many organs, since the Wnt/beta-catenin pathway is so ubiquitous. But instead we found that the effects of this change were limited to specific organs."
The research, as well as finding a new function for the Wnt/beta-catenin pathway, could help increase understanding in infertility.
"If based on these results, we can confirm a link between infertility and this gene, this could lead to a path for the early detection and treatment based on the genetic diagnosis of the infertility," said Yoichi Gondo, who led the research group.
