Dmitri Dozortsev Advanced Fertility Center of Texas, Houston, TX, USA
Whether you believe that life begins at conception or not, the life of each and every one of us began at the pronuclear stage, when two mortal cells came together and transcended into the continuum of immortality of humans as a species. There are many critical stages in the development of a human being but the first cell cycle stands out in its significance, ever more so as we advance our knowledge about it. In this brief article I will discuss the three most crucial events of the first cell cycle, and how they may be affected by embryology practitioner now, and into the future.
First, during natural fertilization, the development is set into motion by calcium ion waves elicited by a factor in the sperm (1), most likely PLC zeta (2), located initially in the head of a spermatozoon and subsequently migrating into the pronucleus. Experimental evidence suggests that full term development is also possible following parthenogenetic activation (3). Those studies, and Ozlil’s work (4) in particular, clearly demonstrate that the duration and amplitude of calcium oscillations affect embryonic developments after implantation. On the other hand, from clinical experience with sharing of donor eggs, we have learned that embryonic development is affected by a fertilizing spermatozoon. Therefore, it is plausible that even though the activation itself is all or nothing phenomenon, the amount of PLC zeta carried by a given sperm cell could affect the duration and amplitude of oscillations and thus produce an effect similar to that observed in Ozil’s experiments. In the same way that intracytoplasmic sperm injection turned out to be more effective than natural fertilization, we may one day find that artificial activation is more efficient and allows more control over the activation process than natural activation.
Telomerase length re-setting
The second crucial event involves the telomeres. There is accumulating evidence of the importance of the length of the telomeres for the life span, probability of cancer, and the length of reproductive life. Because it has been well established that the length of the telomeres shortens with every cell cycle due to inability of telomerase to replicate in 5’-3’ direction (5), it is obvious that at some point during reproduction length of the telemeres must be restored. However, until recently, the stage and mechanism of this restoration remained a complete mystery. It was not until 2007 that this puzzle was solved. It turned out that telomere length abruptly increases during pronuclei stage by a telomerase independent mechanism through sister chromatid exchange (6). This is the only opportunity to reset the length of the telomeres in an individual’s lifetime. It is possible that a better understanding of how telomere length is restored may allow us to extend and improve life span. Only the embryology practitioner will be in a position to accomplish that. Furthermore, we must realize that we may already be unknowingly affecting this process, and will have to wait for a few more decades to see if our in-vitro interventions are affecting life span.