Jerusalem study expected to improve diagnosis and lead to future treatment of infertility

Researchers find genetic key in ovary development and cause of infertility.

By JUDY SIEGEL-ITZKOVICH
Updated: NOVEMBER 9, 2015 02:00
Petri dish [Illustrative] (photo credit: REUTERS)
Petri dish [Illustrative]
(photo credit: REUTERS)
Jerusalem scientists are featured on the cover of the November issue of the prestigious scientific magazine Journal of Clinical Investigation for making a groundbreaking discovery in the field of female fertility.
The scientists located a genetic mechanism vital in the development of ovaries that is expected to make possible the diagnosis of a disease that causes infertility and that prevents girls from entering puberty.
The research, bearing implications for the development of future treatments, was accompanied in the magazine by an editorial written by two world-renowned experts in the fields of human reproductive systems and of Drosophila (fruit flies).
The Jerusalem scientists were Dr. Offer Gerlitz of the Hebrew University Medical Faculty’s Institute for Medical Research Israel-Canada; Hadassah-University Medical Center pediatric endocrinology head Prof. David Zangen; and Shaare Zedek Medical Center medical genetics institute head Prof. Ephrat Levy-Lahad.
Very little is known about the processes involved in the development of the ovary and the egg – responsible for both creating the next generation and for regulating many aspects of female physiology and development – and until now, only a few genes have been identified as important in ovarian development.
Thus any findings in this field are of great importance to understanding infertility and fertility.
The research team discovered an extended family descended from a common ancestor in which four female cousins suffered from the lack of ovarian development, even though each possessed two X chromosomes, as does a normal woman. As a result of their lack of sex hormones, these girls did not undergo the regular process of puberty. The women were all treated with replacement hormones, which allowed them to reach a normal height and to experience a monthly period.
The scientists searched for regions of genetic commonality among them, but not shared by their healthy relatives, and also sequenced the entirety of their coding genomes. They identified a mutation in a gene that differentiated between the affected patients and their healthy relatives. This gene codes for a protein that is an key component of the channel linking the cell’s nucleus (where the DNA is situated) and its cytoplasm (the remainder of the cell’s parts).
At this stage, the search began for a model system to provide experimental proof that linked the suspect mutation to the observed lack of ovaries. As the reproductive process, they explained, is similar in the fruit fly and humans, the researchers generated flies with the mutation.
To the researchers’ amazement, many of the female flies also demonstrated significant impairment in ovarian development.
The mutant female flies laid eggs, however quite minimally, and the majority of the eggs were deformed and did not hatch. This proved the critical importance of the mutation and gene in the development of the ovary and in the formation of the egg cell.
Gerlitz said the discovery will allow for the diagnosis of both patients and carriers of the disease.
Prenatal diagnosis will also be possible. Gerlitz added, “Potentially, it could also lead to a method of treatment for problems of infertility and premature ovarian failure.”