Mammalian sexual reproduction- Two mother mice and their healthy biological offspring

We all know of the classical model of sexual reproduction- The haploid chromosome sets of paternal and maternal gametes fuse together after 5 minutes of a steamy, unprotected tango, to form a diploid cell. This diploid cell then undergoes mitosis until we get the formation of a totipotent mass of embryonic stem cells.

But what if possibilities existed outside of the natural order? What if it doesn’t necessarily ‘take a man and a woman’? What if it we could procreate using two unisex haploid cells and a fancy laboratory?

On Thursday October 11th 2018 the Chinese Academy of Science made a breakthrough in field of sexual reproduction.

The terms Parthenogenesis and Androgenesis refer to the formation of an embryonic stem cell from solely respectively maternal or paternal DNA. Rare in nature and near non-existent amongst mammals, this is how the Chinese Academy of Science managed to produce generations of both bimaternal and bipaternal mice.

How modern humanity replicates Parthenogenesis and Androgenesis

Step 1: Formation of the haploid stem cell

How does one fool a haploid cell into duplicating as if it were diploid? Currently, there are two methods.

One method utilizes a cocktail of chemical activators ,that initiate mitosis in an unfertilized egg cell whilst the second involves the extraction of the unwanted paternal or maternal pronuclei once the haploid cells fuse to form a diploid cell, as per the classical method of sexual reproduction. Both methods result in a haploid embryonic stem cell, which, through a range of potential laboratory techniques, are modified and inserted into a parent cell.

Now, it seems simple so far right? Well, this is where it starts to get sticky; cue genomic imprinting.

In the classical model of sexual reproduction there exists a key regulatory mechanism called
 genomic imprinting. Paternal and Maternal genes interact so that certain genes active in, for instance, the maternal set, are deactivated by their paternal counterpart. Though we are far from understanding the specific pathways of genomic imprinting, we now
 understand that it is invaluable to the long term health and survival of growth of offspring

Now back to the mice…

In a previous trial, regions within two sets of maternal genes (normally deactivated due to genomic imprinting) were accidentally expressed; resulting in a generation of mice pups that displayed both abnormal growth and severely shortened lifespans.

On the other hand, the most successful trial to date involved the use of genetic engineering. Researchers subjected a maternal haploid cell to imprinting region deletion, inorder replicate genomic imprinting. The deletion of several imprinting regions manufactured a set of maternal genes that exhibited the regulatory behaviours of paternal genes. This ‘paternalized’ haploid pronuclei was then fused with an unfertilized egg to form a diploid cell. The results yielded 29 out of 210 pups that healthily matured into adulthood. Some even went on to produce healthy offspring by means of the classical model of sexual reproduction

The process of producing bipaternal offspring is more complicated; It involves 7 imprinting region deletions of a paternal pronuclei that’s inserted into an empty sperm cell that goes on to fuse with an enucleated egg cell. The most successful trial yielded only 12 live bipaternal mice were produced out of 477 embryonic haploid cells. Of the 12,
 only 2 made past the 48 hour mark. Neither reached adulthood.
Though the difference in success between ESCs (Embryonic Stem cells) is yet to be fully understood, this successful Generation of uniparental mice poses a significant step forward in regards of our understanding of why mammals
 are only capable of sexual reproduction. Though  human haploid embryonic stem cells have been generated, it remains unthinkable to generate human baby in this manner, regardless of how easy it may be. Moreover,  a likelihood exists that the imprinted regions deleted in mice are dissimilar to that of humans. It is believed that attempting to produce a “lesbian” or “gay” baby through these methods would be heavily time-consuming and would only safely yield a generation of modified ESCs. Though astounding, these current methods still present little likelihood of successfully producing live individuals (for example only 2.5% for bipaternal reproduction in mice, which may be lower still in humans).”

Thank you for reading!

By Sam Quitua

http://www.sciencemediacentre.org/expert-reaction-to-research-allowing-mouse-pups-to-be-born-from-same-sex-parents/ 
https://www.youtube.com/watch?v=1BdK2UnZhxA
https://www.ncbi.nlm.nih.gov/m/pubmed/30318303/

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