“Then Hashem said to Avraham, “Why did Sara laugh, saying, ‘Shall I in truth bear a child, old as I am?’” Genesis 18:13 (The Israel Bible™)
So far, it has worked in tiny worms called C. elegans, but the discovery of a gene that controls the development of eggs in these invertebrates could eventually help women to control their biological clock.
Dr. Jonathan Tzur and his research associate Dr. Hanna Achache of the Hebrew University genetics department used genetic engineering to discover that the gene allows the shutting down of a cellular mechanism that promotes the development of eggs. Control of this mechanism may in the future contribute to halting women’s biological clock who could then give birth when they are older, as the study of this type of worm has been very helpful in the past in understanding human genetics.
The main cause of birth defects, unplanned miscarriages, and infertility in humans is the aging of oocytes (egg cells). As women get older, changes in their eggs prevent them from developing normally. In fact, there are fertility experts who believe that for most women, from the age of 35, most of their eggs will not be able to produce a healthy baby.
In-vitro fertilization makes possible the selection of eggs that have been able to develop normally, but the chances of finding such eggs from the age of 42 are almost zero in most cases. In the Western world, the age of women when they have their first baby birth is rising, so it is important to find a way to help women gain more freedom in their family choices. This is why many researchers around the world are trying to find out what controls the rate of ovarian development and aging.
The new study conducted by geneticists at the university’s Institute of Life Sciences was conducted in collaboration with researchers at Harvard Medical School and was recently published in the journal Genetics.
The researchers chose to use the C. elegans worm because the eggs mature in about a week. “We scanned the change in the expression of some 20,000 genes during the development of the eggs and found that the expression of the gene H2 occurs at the critical points of development. They used CRISPR-Ca9s technology to completely remove this gene from the genome. “These worms have changed, and they have been less fertile,” reported Tzur.
The researchers found that many of the eggs in the worms without the gene undergo programmed cell death – apoptosis – a cellular “suicide,” so these worms have fewer eggs. The use of genetic analysis has shown that the H2 gene controls a major biochemical signaling pathway in development called “map kinase.”
The role of gene H2 is to reduce the expression of the biochemical pathway at the right time and place during egg development, as well as in the adult egg. “What surprised us was that if we did not protect young eggs, they would have characteristics of very old oocytes, which suggest that control of this biochemical pathway in the adult egg can control and ‘stop’ its biological clock,” Tzur explained.
‘The researchers are currently using genetic manipulations to boost the expression of the biochemical pathway in the eggs and see if their fertility is maintained for longer periods of time. Positive results in this study will open the door to understanding how to control the rate of egg aging and perhaps, in the future, to slow it down, allowing women to give birth even at older ages. The researchers presented these results at world-leading conferences, with the most recent results being presented in about two weeks at the annual meeting of the Israel Fertility Research Association in Tel Aviv.