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To us mere humans, the concept of parthenogenesis is alien. From early in school, we are taught that creating new mammal life requires sperm to fertilize an egg, which then begins an eruption of developmental processes to become an embryo. Parthenogenesis, the reproduction method of choice for some animals and plants, does away with all of that – who needs a male when the egg can spontaneously become an embryo?
Except it isn’t so easy for mammals, owing to an important genetic process called imprinting. Imprinting involves specific markers inherited by our parents, which can affect how certain genes are expressed; a gene may be present in our DNA, but imprinting can decide if it is turned "on", or rendered completely useless by turning it "off".
For parthenogenesis, imprinting has been a huge gateway preventing mammals from asexually reproducing. Now, in a study published in the journal Developmental Biology, researchers from Shanghai Jiao Tong University have successfully created viable mammalian offspring from an unfertilized egg by manually modifying the sites usually imprinted, opening massive avenues in everything from agriculture to research.
Bypassing imprinting and developing offspring from an unfertilized egg is an extremely challenging task in mammals. Imprinting acts on specific sites in the genome, called imprinting control regions, through the process of methylation, which adds a specific chemical group to DNA to prevent proteins from "reading" the gene, essentially turning it off. Targeting these sites requires accurate addition or removal of methyl groups while leaving the underlying DNA code unchanged, a process that until now has proven difficult.
The team of researchers led by Yanchang Wei utilized single guide RNA (sgRNA), which act as homing beacons to specific regions of DNA, and attached either Cas9 – which you may recognize from CRISPR-Cas9 technology – or messenger RNA (mRNA) to add a methyl group or take it away from the imprinting control region, respectively.
Acting on seven specific sites, the researchers rewrote the imprinting on one copy of each gene but not the other, before stimulating the egg to begin development into an embryo. The embryo kept the edited imprinting as if it was naturally inherited, and when implanted into a female mouse, began developing successfully. Out of 192 embryos transferred, 14 developed into pregnancy, and three were birthed as live pups. Unfortunately, only one of the pups survived to adulthood, highlighting the need for improvement in the process.
However, the growth of a viable offspring, which went on to have offspring of its own, demonstrates the first case of parthenogenesis from an unfertilized mammalian egg. Such results may have huge implications from the targeted imprinting alone, but if parthenogenesis can be refined to produce more successful pups, may have even wider applications in medicinal research, agriculture, and more.
While it is a massive milestone for genetic research, parthenogenesis in mammals has a long way to go. Such epigenetic imprinting could have off-target effects, in which it changes the DNA in portions of the genome that researchers are not targeting, and this needs to be fully understood before it can be applied widely. CRISPR-Cas9 research is facing similar challenges, although at a much more developed stage.
