As we saw last week, an embryonic stem cell is a form of pluripotent stem cell. Pluripotent stem cells are stem cells which can, in theory, give rise to mature cells derived from any of the three embryonic germ layers; in other words, any mature cell type in the body. Since an understanding of early human embryology is essential to battling in the stem cell wars (along with a lot of other battles), it’s time to review a bit.
In the beginning, there is mittelschmerz, that “middle pain” which so often occurs, along with ovulation, a couple of weeks after the end of menstruation. At ovulation, the ovary spits out a mature oocyte - an egg - and it lands in the opening to the fallopian tube, the muscular tube connecting the ovary with the uterus. The tube begins its peristalsis, the gentle muscular contractions milking the oocyte down the tube towards the womb. On the way, the oocyte may find itself within a swarm of sperm, the sperm having swum all the way up there after being left within the vagina. One of these sperm may penetrate the zona pellucida, the thick covering around the egg. Since the genes in the egg came from the mother, and the genes in the sperm came from the father, if this penetration of egg by sperm is successful, the mother’s genes are combined with the father’s genes, and a new, genetically and physiologically distinct single celled creature comes into existence, a being which is genetically human, and neither mother nor father. This is the moment of conception. It isn’t really a moment, of course, as the process of sorting of the parental gene contributions into a new genotype takes many hours. Nevertheless, a new single celled being results from this process, a totipotent stem cell (because it gives rise to all the cell types of the body, as well as the cells of the placenta), the human zygote.
Normally, in vivo (in life) conception takes place within the fallopian tube. After the first 36 hours or so of its new life, the single celled zygote divides into two cells. After another 36 hours, the two cells become four, then eight, and so on. Meanwhile, this embryo is now known as a morula, a “ball of grapes” (all of these stages, from zygote on up to, but not including, the fetus, are known as embryos), and is now making its way down the tube. The passage from ovary to uterus through the tube takes 5 to 7 days, and during this time the embryo has developed from the single celled zygote to the multi-celled morula. At the morula stage, the cells are already they are beginning to differentiate. The outer layer will become the trophoectoderm, the precursor to the placenta, while a central cavity is beginning to form within the inner mass of cells. The cavity will be known as the blastocoel, and once it forms, the embryo will be known as a blastocyst. At this point, about 5 to 7 days after conception, the little human embryo comes to the end of the fallopian tube, and enters the uterus.
After floating around for a day or two in the uterus, the embryo implants. By this point, the trophoectoderm, the outer shell of cells, has begun to form what will become the placenta. Meanwhile, the inner cavity, the blastocoel, has enlarged, and the inner cell mass, numbering around 30 cells, has begun to develop into two distinct layers. One of these layers will become the structures of the amniotic cavity, which will support and cushion the growing child throughout intrauterine life. By the beginning of the third week after conception, gastrulation occurs, where the primitive streak, the precursor to the central nervous system, appears. Now, the other layer of the inner cell mass begins to develop into the three germ layers we spoke of earlier, the precursors to all the mature cell types within the body. Not too long after this, a beating heart can be found.
There’s two important points to keep in mind about the sequence we’ve just gone through. First: conception, in vivo, occurs in the fallopian tube. Second: for the first 8 or 9 days of a human embryo’s existence, it’s free floating. The human embryo, from the zygote through the morula to the blastocyst stage, is increasingly being referred to as the pre-implantation embryo.
Everything we’ve just described occurs in vivo. However, conception of a zygote, and growth of that zygote up through the blastocyst stage, also can occur in vitro, in a petri dish. In fact, in is done, routinely, thousands of times a year, in in vitro fertilization (IVF) clinics all across these United States. IVF is a billion dollar business, but that’s beyond the scope of this piece. Suffice it to say that oocytes are obtained from a woman, placed in a petri dish with sperm obtained from a man, and viola! Zygotes. The zygotes are allowed to develop in the dish to the morula stage, and are then graded according to quality (I’m not kidding). The best ones are selected for implantation in some woman’s womb, where they may (or may not) grow into full term babies. The rest go into the freezer. How many of these leftovers are there in freezers across our land? No one knows for sure, but best estimates from folks within the IVF industry put the number at around 400,000. What happens to these frozen IVF leftovers? Most are just sitting there, waiting. Some, though, are obtained by researchers, who will use them to obtain embryonic stem cells. And with this background, we will let the matter rest until next time.