It is commonly believed that the division processes for cells of the body and reproductive system are distinct, but a new study shines a new light upon the possibility that they might actually be entangled.
Mitosis is a cellular replication process that yields two cells identical to both each other and the cell from which they divided. Genetic material inside this initial cell is first duplicated and the whole cell is then split. This results in two diploid cells that contain all 46 chromosomes. This process happens with every cell in the body except gametes, the sex cells of the body, which undergo meiosis. In meiosis, the number of chromosomes is halved and the resulting gametes have 23 chromosomes instead of 46. The process has two phases; the first is similar to mitosis and results in two daughter cells with 46 chromosomes each. In the second, chromosomes are not replicated and each daughter cell simply divides, resulting in a total of four haploid cells containing 23 chromosomes each.
When two gametes come together, they create a cell with the correct amount of chromosomes. These cells were specifically designed to do this job, and the process is possible because of stem cells, or cells from which other cells originate. Each of the 30 trillion cells we have in our body emerges from a stem cell, even the gametes, which ‘stem’ from oogonial stem cells, or OSCs.
“Each of the thirty trillion cells we have in our body emerges from a stem cell, even the gametes, which ‘stem’ from Oogonial stem cells, or OSCs.”
A new study suggests that mouse OSCs and OSCs derived from human adult ovarian tissue exhibit similar characteristics. Alongside a team of scientists from Massachusetts General Hospital, Harvard Medical School, and Saitama Medical School, researchers Yvonne White and Dori Woods, a Northeastern professor, explored whether the ovaries of reproductive-age women have a similar population of germ cells that can produce oocytes in comparison to mouse OSCs. A germ cell is a cell that has the capability to produce an oocyte. Because a cell’s identity depends on how the genes in its DNA are differentially expressed, the team’s goal was to make a protocol to purify the rare cells that undergo mitosis with the same gene expression as a stem cell that will eventually become, or differentiate into, a gamete.
Looking first at the capability of generating oocytes from mouse and human OSCs, they conducted in-vitro experiments and found that mouse OSCs can spontaneously generate into cells that look like oocytes. They tracked the cells with green fluorescent protein, a protein that emits fluorescent light, and confirmed the cells’ identities by testing for oocyte markers. An important finding was that the amount of chromosomal DNA matched that of a haploid cell, meaning that the mouse OSCs underwent both mitosis and meiosis to both replicate and transform from a diploid to a haploid cell, respectively. They then confirmed that the same processes happen in human OSCs using the same methods. This finding reveals that both mouse OSCs and human OSCs have the potential to become oocytes, which can lead to new advancements in fertility preservation.
In addition to testing for in-vitro, researchers used mouse OSCs to investigate whether they could replicate inside living organisms or in vivo. As a control, they used two different methods: one population of OSCs received a mock injection and the other received no injection. They identified diving cells in mice with green fluorescent protein and found that there was no sign of oocyte replication in either of these. They next transplanted human ovary tissue into immunosuppressed mice to see if oocytes were produced. After one to two weeks, they collected three random experimental and transplanted tissue grafts and found the presence of oocytes, meaning that the cells were dividing. Each sample had 15 to 20 oocytes, which is a remarkable number when considering how minute the original amount of OSCs was.
One of the most significant utilizations of this research can be in a fertility aspect; since these oocytes were consistently frozen to be utilized at a later time in vivo, they can also be frozen to be utilized for in vitro establishment, such as IVF or in vitro fertilization. The discovery also allows researchers to use a more physiologically relevant mechanism of cell division in gametes rather than embryonic stem cells or induced pluripotent stem cells. This research can lead to new, more useful mechanisms that will help women with fertility issues.