The maturation of the egg in the woman's ovary and its release during ovulation are a necessary condition for the beginning of pregnancy. The way in which this ripening takes place was recently deciphered, after being considered a mystery for more than 70 years
The maturation of the egg in the woman's ovary and its release during ovulation are a necessary condition for the beginning of pregnancy. The way in which this ripening takes place was recently deciphered, after being considered a mystery for more than 70 years. This insight, which Weizmann Institute of Science scientists participated in obtaining, may make an important contribution to the development of advanced fertility treatments in the future, as well as to the development of improved contraceptives.
The process of ovulation in a woman, that is, the maturation of the egg and its exit from the follicle, occurs under the influence of a hormone called LH, which is secreted from the pituitary gland. But in 1935, Gregory Pincus - later one of the fathers of the birth control pill - discovered a surprising paradox: eggs that have reached the end of their development and have been removed from the follicles mature by themselves in a test tube without any need for hormonal stimulation. Thus was born a mystery that accompanied reproductive researchers for many years.
The series of studies that led to the solution began in the 70s at the Weizmann Institute of Science. Prof. Alex Zafariri from the Department of Biological Control, who was then in the midst of preparing his doctoral thesis, developed a first-of-its-kind experimental system for growing rat follicles in culture. In this system, egg maturation and ovulation processes were dependent on hormonal stimulation, as in live rats. Thus it was possible to examine the exact role of the ovulation hormone LH. In this way, the first evidence was obtained that a molecular messenger called cAMP plays an essential role in the process.
The exact role of the messenger has been clarified in many studies, including the studies of Prof. Nava Dekel from the Weizmann Institute of Science. It was found that the LH hormone causes ovulation by increasing the amount of sperm in the follicle. But inside the egg itself, the messenger works in the opposite way: it is precisely a reduction in its quantity that allows the egg to ripen, and when its level remains constant, the egg's ripening is inhibited.
When he was a post-doctoral researcher in the USA, Prof. Zafariri, together with Prof. Cornelia Channing from the University of Maryland in Baltimore, showed that not only the follicle cells, but also the fluid inside them, prevent egg maturation in vitro. An examination of the liquid led him to the discovery of the cause of the phenomenon: a small peptide named OMI - the acronym for "egg maturation inhibitor".
After returning to Israel and joining the Weizmann Institute of Science, Prof. Tzafariri continued to investigate the maturation of the eggs. In the studies in which he collaborated with Prof. Channing and Prof. Seymour Pomeranz, the scientists found that the follicle cells continuously secrete the peptide that blocks the maturation of the eggs - but the LH hormone overcomes the block. This is how it turned out, that when the egg is grown separately from its follicle or fluid cells, in a test tube, it can mature even without a hormone, simply because there is no OMI to block its maturation.
During a sabbatical year at Stanford University, and in collaboration with Prof. Mario Conti, Prof. Zafariri identified the last link in this chain of events - the last molecular switch in the ripening process. It is an enzyme called PDE3A, which is limited in the ovary only to the egg, and breaks down the chemical messenger (cAMP) in it. The breakdown of this messenger allows, as mentioned, the maturation of the egg, and the scientists have shown that as long as they keep this enzyme in an inactive state, the egg does not mature. The scientists believe that these findings point to the possibility of developing improved contraceptives based on PDE3A, which will not harm the woman's cycle, her hormonal status, and in fact the release of the egg - which is not suitable for fertilization.
In fact, each of these processes is conducted in several complex stages, with checks and balances. Why is it necessary to have such a complex control over the maturation of the eggs? Prof. Tzafariri: "The complexity ensures that the process is properly controlled, and timed in such a way as to ensure that an egg will ripen at the appropriate time for fertilization and a successful pregnancy, thus ensuring the existence of the species and the continuation of life."
News from the front
The peptide that Prof. Zafariri called OMI was recently identified by Prof. John Efig and his group at the Jackson Laboratory in Bar Harbor, Maine, USA. This was reported in the scientific journal Science. The size of the peptide - already known in other systems as NPC - corresponds to the expectations of Prof. Zafariri and his colleagues, and it is indeed continuously secreted from the follicle cells. Stimulation of ovulation by the LH stops the formation of the NPC in the follicle cells. As a result, a complex chain of molecular events (in which all the "players" described here are involved) is activated in the follicle, leading to the maturation of the egg.
Peres Bhatt
Prof. Tzafariri recently won the Bhat Prize for a non-fiction book, awarded on behalf of the Haifa University Publishing House. The prize is awarded every year to "a theoretical, original and high-quality manuscript, written in Hebrew and not published elsewhere, and which is of interest to a broad and educated public". Prof. Tzafariri won the prize for his book "Man as an animal? The controversy over biomedical experiments on animals". The book discusses the public debate about animal experiments in biomedical research in Western countries and Israel, from a scientist's point of view. The essay describes the philosophical and moral approaches regarding the relationship between man and animals, as well as the monotheistic religions' treatment of the subject, emphasizing the approach of the Jewish sources and practice. The book will be published by the book publishing house of the University of Haifa, in cooperation with Yediot Book Publishing.
