After carrying out a research study, the results does not only broaden the understanding between the urogenital tract and human reproductive health, but has also broaden more insight on previous unidentified contribution of the human microbiota to genetic abnormalities,".
"The idea is to explore the mechanisms findings and their potential implications for preventing and treating chromosomal abnormalities and genetic diseases," said co-lead author Giovannino Silvestri, PhD, former Research Associate of Medicine in UMSOM's IHV.
The human microbiota is known to affect metabolism and susceptible to infectious diseases, immune system regulation, and more.
One of these bacterial components, Mycoplasmas, have been linked to various cancers.
The research team has been studying one Mycoplasma protein, DnaK, which belongs to a family of proteins that safeguards other bacterial proteins against damage and aids in their folding when they are newly made, acting as a so-called 'chaperone.'
However, while this protein is advantageous for bacteria, its effects on animal cells are less favorable.
To this regard, the team had previously demonstrated that this DnaK is taken up by the body's cells and it interferes with key proteins involved in preserving DNA integrity and in cancer prevention, such as the tumor suppressor protein p53.
Latest study, researchers created mice that make the DnaK protein normally produced by the bacterium Mycoplasma fermentans.
These mice with exposure to DnaK accrued genomic instability in which entire sections of the genome were duplicated or deleted, resulting in mice with varying numbers of copies of certain genes.
The team noticed that some of these mice from 3-5 weeks of age had problems with movement and coordination.
They found that these mice have a deletion in the Grid2 gene, which in humans leads to the rare genetic disease known as spinocerebellar ataxia-18 (SCAR18) that causes delayed development of skilled movements and intellectual disabilities.
"Remarkably, this instance marks the first time a mouse model successfully recapitulated a human genetic disease de novo, showcasing this model's potential for further cancer biology research," said Dr. Zella.
More than a third of the female mice that made the DnaK protein were unable to get pregnant. Additionally, more than 20 percent of the pups born from moms with the DnaK protein had some sort of birth defect/deformity.
"The occurrences of genomic instability, in the form of increased number of copy number variations, could explain the decreased fertility and the increased instances of abnormally developed fetuses we observed upon DnaK exposure," said Dr. Gallo.
"These data build upon our initial work which discovered the disruptive role of DnaK on key proteins involved in the proper repair of damaged DNA, which are also known to play a role in the onset of copy number variations.
The ongoing commitment is to better understand the potential implications of these findings in cellular transformation and cancer."
UMSOM Dean Mark T. Gladwin, MD, who is also Vice President for Medical Affairs, University of Maryland, Baltimore and the John Z. and Akiko K. Bowers
Distinguished Professor, commended the work. "The researchers raise a significant question regarding whether DnaK can interfere with fetal development in humans.
An important next step would be to investigate whether neutralizing either the bacteria or this protein could preserve fertility and prevent certain birth defects," he said.
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