New Hebrew U. Research Study of Zebrafish Ovaries Reveals New Structure That Has Implications for Human Reproduction

JERUSALEM, May 16, 2022... Using new advanced technologies developed in their lab, Hebrew University researchers were able to watch in real-time as a cluster of immature egg cells (oocytes) progressed towards maturity, finding a previously unobserved structure emerging from the cell which could have reproductive implications for human reproduction. The findings were just published in Science.

The cilium appears as a twisted fiber extended into the mass of surrounding eggs. Further research showed these cilia play an essential role in chromosomal organization within oocytes. Moreover, the researchers identified the same structure within the sperm cells of zebrafish, in mouse oocytes and sperm.

Dr. Yaniv Elkouby lab at the Hebrew University of Jerusalem (HU)’s Faculty of Medicine, focuses on the development of the immature egg cells (oocytes) of zebrafish. Humans share about 70% of gene with zebrafish and other similarities that make these small transparent fish an ideal animal model for the study of many human diseases and biological processes.

Failure of chromosomal organization within human egg and sperm cells result in miscarriages and infertility, however, the mechanisms controlling these processes are not understood. Furthermore, defects in cilia formation and function cause genetic disorders called ciliopathies, in which patients suffer from deficient fertility and, in tragic cases, babies and children suffer from severe developmental disorders. These were attributed to the failure of other types of cilia. The newly identified cilium provides an additional explanation for these deficiencies. “Identifying mechanisms moves medical research one step closer to finding solutions,” Elkouby says.

Elkouby explains that to explore the function of these new cilia, his team had to develop new, advanced methodologies. "We used a repertory of methods, including advanced quantitative and live microscopy, innovative three-dimensional high-resolution imaging, ovary organ culture, manipulations using laser excision, and genetic analyses of multiple mutants."

His team was able to identify that the newly identified cilium is connected to a "cable-system" within the cell that organizes the chromosomes by mechanically pulling on them. This process is an essential part determining the formation of a fully functional egg that can give rise to healthy offspring. The external cilium anchors the entire cable-system machinery within the egg enabling the essential precise dynamics of the chromosomes to be achieved.

This ground-breaking research, says Elkouby, "was a real team-effort, co-led by two talented doctoral students: Avishag Mytlis and Vineet Kumar. We also collaborated with the lab of our partner Dr. Sudipto Roy at the institute of Molecular and Cell Biology, Proteos, Singpore, and with the lab of Dr. Ruxandra Bachmann-Gagescu, University of Zurich."