The marvels of science underpinned by the advances in gene editing have helped scientists achieve several feats, but progeny and sexual reproduction are still unexplored realms. One such areas has been sexual reproduction in mammals, where researchers are trying hard to achieve the viability of production of the offspring from the organism of the same sex. Advances in this direction are in part constrained by worldwide ethical concerns and largely due to barriers related to the health of offspring. One of the key barriers is the difficulty to overcome imprinting. A team of scientists from the Chinese Academy of Sciences have been successful in generating mouse pups with two mothers (the first time in 2004), but the healthy progeny of the mice from two fathers still challenges them. In a new study, the researchers were able to produce healthy mouse pups from two female mice. However, this is the first time, this feat has been achieved from a pair of male mice. The team of researchers using the same gene editing method they used before and exploiting pluripotent stem (iPS) cells were able to produce mice pups, male as well female mice, with two father mice. Sadly, the mice pups born from two males died soon after the birth.
The details of the study are published in the journal Cell Stem Cell on October 11, 2018.
Researchers overcame Constraints related to Genomic Imprinting using Stem Cells and Gene Editing
The key challenge in the viability of the progeny in mammals with a placenta with the same sex is imbalances in genomic imprinting (or simply imprinting). In humans, the phenomenon occurs during sperm and egg development results in offspring copying one set of chromosomes from dad and the other from the mom from the 23 pairs of chromosomes each of the parents possess. Typically, this phenomenon, not fully understood, would result in epigenetic differences from gametogenesis, which was responsible for the production of healthy offspring in humans. In mice, the scientists were able to overcome this differences before using haploid embryonic stem cells (ESCs), which helped them generate viable bimaternal female. The method essentially helped them delete three imprinting areas of the genome from the ESCs to erase genomic imprinting. Furthermore, they exploited CRISPR-Cas9 targeted genome editing to remove troublesome genes.
Production of Mouse Pups from Male Mice not without Problems, Pups died soon after Birth
Unsurprisingly, the production of mice pups with two male mice since male fathers brought unique set of problems as the male lacked eggs. The researchers modified the egg with the haploid ESCs and nuclear transfer of the immature egg to achieve the bipaternal reproduction; however, the pups could survive for long.
The implications of the result is yet to be realized for humans and the scientists don’t rule out the possibility. The findings are expected to be breakthrough for mammalian reproduction and assisted reproductive technology.