Mammalian parthenogenesis creates viable offspring from unfertilized egg
Erin Patricia D. Del Rosario
In a paper published on March 7, 2022, in Proceedings of the National Academy of Sciences, a team of scientists from China is the first to successfully create viable offspring born from a single unfertilized mammalian egg via parthenogenesis.
Without the need for fertilization, the single oocyte gave rise to three parthenogenetic mouse pups, one of which survived to adulthood with normal reproductive performance and even gave birth to its own viable offspring.
The research team of Cai-Rong Yang and Zhen-Ao Zhao, led by Yanchang Wei, demonstrates this successful parthenogenesis through the targeted epigenetic editing of critical imprinting control regions.
Parthenogenesis is a means of producing offspring solely from maternal germ cells with the embryo developing from a single unfertilized egg.
Although parthenogenesis naturally occurs in small invertebrates, such as bees, mites, and aphids, and even vertebrates like fish and reptiles, mammals do not exhibit this mode of reproduction.
Successful mammalian creation of offspring requires bi-parental sexual reproduction which involves the fusion of both maternal and paternal genomes, resulting in an offspring with genetic material from both parents.
The genetic differences between the two parents, including sex-specific epigenetic marks, allow for the unequal expression of imprinted genes from the maternal and paternal alleles.
Genomic imprinting provides a balance in the gene expression between the two parents, playing a critical role in the regulation of mammalian development and the consequent viability of the offspring.
This phenomenon has proved to be a reproductive barrier as previous studies that have attempted to derive a diploid genome from only one sex via parthenogenesis were shown to be incapable of supporting embryo development.
Parthenogenetic embryos encounter a problem with gene dysregulation from the two-fold establishment of maternal-specific and paternal-specific imprints, which can lead to severe developmental disorders and embryonic or postnatal fatality.
The team of Yanchang Wei, Cai-Rong Yang, and Zhen-Ao Zhao overcame this problem of imprinted genes by using CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology to target imprinting control regions and edit DNA methylated regions known to be necessary for embryonic development.
With the use of CRISPR, the researchers edited the genes of the mouse to resemble that of a male parent during regular fertilization, injected an enzyme into the egg to make its genes mimic those of a fertilized egg, and implanted the egg into the uterus where it was allowed to develop into a fetus.
A total of 389 oocytes were edited, around 58.4% of which formed diploid zygotes following parthenogenetic activation, with 85% of the parthenotes developing into blastocysts transferred into the foster mothers.
Three live mice were recovered, two of which died during the first 24 hours, but the surviving female grew to adulthood displaying correct genomic imprinting patterns across all control regions and was able to mate and give birth to normal pups.
Wei, Yang, and Zhao noted that the surviving parthenogenetic mouse exhibited postnatal growth delays that were potentially associated with another critical paternally methylated imprinting control region that was left unedited.
The researchers emphasized that the success of mammalian parthenogenesis can pave the way for several agricultural, research, and medicinal applications.
