Monday 3 August 2020

The Science Behind the Artificial Activation of Egg Cells

Briefly mentioned on our biology specification was the idea that human egg cells could be artificially activated to divide, without any input from sperm, essentially creating a source of embryonic stem cells whilst bypassing the ethical issues associated with such cells. That was as far as the textbook cared to explain so I went on a bit of a Google deep-dive to find out more about the process behind this.


Karl Swann is the Chair of Reproductive Cell Biology in the School of Medicine at Cardiff University. Swann’s team tricked egg cells into dividing by injecting them with an enzyme (phospholipase C-zeta) produced by sperm during natural fertilisation. Egg cells contain two sets of chromosomes and during natural fertilisation one of these is typically discarded within two hours; the team used a standard chemical treatment to prevent this resulting in a parthenogenetic embryo - one that contains no paternal chromosomes and instead has two sets from the mother - that appears to undergo the same changes as a natural embryo.

The activated eggs divide for around five days until they reach the blastocyst stage (at which they are around 100 cells strong) when they should in theory provide a source of stem cells. The embryos that are created from this process cannot develop into babies since no sperm was involved in the activation. Therefore, this sidesteps the ethical controversy around the destruction of potential human life, since genetically, these cells are not capable of life. The hope is that the pluripotency of these cells can be used to treat a range of diseases.

The enzyme used might also help women become pregnant through IVF. One IVF technique injects sperm directly into the eggs in a lab and then implants them into the uterus. Unsuccessful attempts occur when the embryos never begin dividing and it is thought this could be due to the sperm having defective PLC-zeta. Adding the enzyme artificially might start them dividing.

This isn’t the only method being trialled, in fact there are many routes to getting an ethical source of stem cells that are being looked into. For example, a team led by David Wininger grew parthenogenetic human blastocysts by stimulating eggs chemically and this approach involved triggering a calcium wave.

Another revolutionary and ethically optimal option would be the creation of embryos specifically for the purpose of isolating stem cells via ‘nuclear transfer’ or ‘therapeutic cloning’. This method involves the insertion of the nucleus of a somatic cell (any cell of a living organism other than the reproductive cells) into an enucleated unfertilised egg (one that has had the nucleus removed). Since the nuclear DNA of the cells is derived from a somatic cell of the patient intending to receive the transplant, the chances of tissue rejection are greatly reduced. The egg in this case is not fertilised. Instead it receives maternal and paternal genomes from the somatic cell nucleus. Since by some definitions an embryo is the result of fertilization of an egg by sperm, there is no absolute consensus that nuclear transfer gives rise to an embryo. Therefore, this is another way around the ethical issues of the embryonic stem cells having a right to life, since the artificially created ‘embryo’ wouldn’t produce a fetus if placed in the womb.


(An oocyte is a cell in an ovary which may undergo meiotic division to form an ovum. Autologous tissue is tissue that comes from the host itself - this relates to the reduced chance of rejection since the body recognises the new tissue as its own).

The ethical guidelines around this subject are also up for debate and it has previously been proposed that the criteria applied to organ donation could also be applied to the collection of embryonic stem cells from non-viable (essentially dead) human embryos produced during routine IVF procedures. It has been shown that such embryos do not continue normal embryonic development once in culture, yet most of them contain a substantial number of living cells on day 6 of culture, which suggests that non-viable embryos could provide reliable stem cell lines.


Sources:

https://www.newscientist.com/article/dn6733-zapped-human-eggs-divide-without-sperm/

https://academic.oup.com/humrep/article/18/4/672/596542

https://www.sciencedirect.com/science/article/abs/pii/S1472648310602702


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