New Research Sheds Light on Causes of Reproductive Disorders, Infertility, Miscarriages and Birth Defects

Researchers from Rutgers University, Memorial Sloan Kettering Cancer Center, Rockefeller University and Cornell University are teaming up to examine how processes that regulate gene expression and chromosomal behaviors can lead to problems with health, including cancer, birth defects, miscarriages and infertility.

Cells undergo a remarkable transformation process to form eggs and sperm, which upon fertilization can form an entire organism. A key step in this transformation involves meiosis, a cell division that halves the genomic content of cells. During the early stages of egg and sperm development, cells divide by mitosis, the process used by most cells in our body. They then undergo a complete remodeling of the gene expression landscape and move on to meiosis. Misregulation of the transition from mitosis to meiosis can lead to tumor-like growth, depletion of the pool of reproductive cells, or failure of meiosis.

In the new Rutgers-led study in the journal Genes & Development, researchers applied powerful methods to map genome-wide protein-RNA interactions and innovative mouse genetic mutants to define how the RNA helicase, YTHDC2, binds to RNA and controls expression genes to regulate meiosis. YTHDC2 and its interacting protein partners form an essential pathway that controls the transition from mitosis to meiosis. Prior to this study, little was known about the mechanisms regulating this switch in mammals.

“Our work sheds light on the genetic and molecular mechanisms necessary for normal meiosis, which is a critical step in understanding how and why these processes go awry and lead to reproductive disorders,” said Devanshi Jain, principal investigator of Studies and Assistant Professor of Genetics in the School of Arts and Sciences (SAS) at Rutgers University in New Brunswick. “Furthermore, as YTHDC2 has been implicated in multiple diseases, particularly cancers, our work will also have broad implications in these areas.”

Jain said this new study, along with ongoing research at the Rutgers-hosted Jain Lab, explores the genetic and molecular mechanisms of meiosis, as well as the processes that regulate gene expression and chromosomal behaviors. Jain Lab researchers are using the mouse model system to explore these fundamental aspects of cell biology.

“Understanding meiosis is of paramount importance to reproductive health, as errors in meiosis can lead to reproductive cell death and infertility,” Jain said. “In the future, we plan to dig deeper into the molecular mechanisms of the YTHDC2 pathway and its control of gene expression. We also continue to study other fundamental aspects of the regulation of meiosis.

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Material provided by Rutgers University. Note: Content may be edited for style and length.

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