Researchers from the University of Maryland School of Maryland’s Institute of Human Virology (IHV) have published groundbreaking findings on the role of urinary and genital tract microbiota in adverse pregnancy outcomes and genomic instability during fetal development.
Their study, featured in the Proceedings of the National Academy of Sciences (PNAS) on July 17, establishes a link between genomic instability and a protein from Mycoplasma fermentans, a bacterium commonly found in the urogenital tract. This bacterial protein was found to reduce fertility in mother mice and led to more birth defects in their offspring.
The research, led by Davide Zella, Ph.D., and Robert Gallo, MD, sheds light on the interplay between urogenital microbiota and human reproductive health. The team aims to delve further into the mechanisms underlying these findings and their potential implications in preventing and treating genetic abnormalities and diseases.
The human microbiota affects various aspects of health, such as metabolism, susceptibility to infectious diseases, and immune system regulation. Mycoplasmas, a type of bacteria, have been linked to different cancers.
The researchers focused on a Mycoplasma protein called DnaK, which assists bacterial proteins in folding and protecting them against damage. However, its effects on animal cells are less favorable. Previous research showed that DnaK interferes with proteins involved in preserving DNA integrity and cancer prevention.
For the latest study, the researchers created mice that produced the DnaK protein found in Mycoplasma fermentans. These mice experienced genomic instability, leading to duplications or deletions of entire genome sections, resulting in varying numbers of gene copies.
Some mice exhibited movement and coordination problems due to a deletion in the Grid2 gene, similar to a rare genetic disease called spinocerebellar ataxia-18 (SCAR18) in humans, causing delayed development of skilled movements and intellectual disabilities.
More than a third of the female mice producing DnaK were unable to get pregnant, and over 20% of the pups born from these mice had birth defects.
The researchers believe that genomic instability, manifested by increased copy number variations, may explain the reduced fertility and increased instances of abnormal fetal development observed with DnaK exposure.
The study represents a significant milestone as the mouse model successfully replicated a human genetic disease, highlighting its potential for cancer biology research.
UMSOM Dean Mark T. Gladwin, MD, praised the research, emphasizing the importance of investigating whether neutralizing the bacteria or the DnaK protein could preserve fertility and prevent birth defects in humans.