Mice with two fathers have been successfully created and survived to adulthood following a complex set of experiments led by a team in China. The breakthrough, conducted by Zhi-Kun Li and his colleagues at the Chinese Academy of Sciences in Beijing, utilized CRISPR gene-editing technology to bypass a biological phenomenon known as genomic imprinting. This process ensures that certain genes are expressed differently depending on whether they come from the mother or the father, and it has been a significant barrier in attempts to create animals from same-sex parents. Their findings, published in Cell Stem Cell and reported by MIT Technology Review, represent a major milestone in reproductive biology.
In previous attempts to create mice with two fathers, researchers faced the challenge that embryos needed input from both maternal and paternal genes for proper development. One of the earlier attempts in the 1980s, where scientists injected sperm DNA into an egg cell, resulted in failure because the imprinted genes required for embryonic growth were not balanced. Li’s team took a novel approach by using gene editing to knock out 20 imprinted genes that are crucial for embryo development, effectively removing the need for the maternal contribution. After culturing stem cells from sperm DNA and editing the genes, the team injected these gene-edited cells into enucleated egg cells (cells with their nuclei removed) alongside sperm cells. These resulting embryos, which contained only paternal DNA, were then transferred into the uteruses of female mice.
While the technique showed promise, the success rate was low. Of the 164 embryos implanted, only seven survived to birth. These mice grew to be larger than normal, with enlarged organs and shorter lifespans, and they were infertile. Despite these abnormalities, the fact that some of the mice survived into adulthood was considered a remarkable achievement. Kotaro Sasaki, a developmental biologist at the University of Pennsylvania, praised the team’s ability to avoid imprinted gene defects, noting that this was the second successful method of creating mice from two males. This research builds on previous work by Katsuhiko Hayashi, who used a different approach of converting male cells into egg cells to create bi-paternal embryos.
However, experts caution that such methods are not yet feasible for humans. Li himself emphasized that editing 20 imprinted genes in humans would be unethical and not viable, as it could lead to unhealthy or non-viable individuals. Sasaki also noted the significant risks involved in gene editing human cells, especially since many of the procedures used in the study are not established for human reproductive cells. The technical challenges are immense, and the consequences of knocking out human genes could have unforeseen health impacts.
This study provides valuable insight into the role of imprinting in development, offering clues about the balance between paternal and maternal genes. Research has shown that mice with two mothers tend to be smaller and live longer, while the mice created in this study with two fathers grew larger and had shorter lifespans. These findings suggest that paternal imprinted genes may promote growth, while maternal imprinted genes may help regulate it. Despite the ethical and scientific hurdles that remain, this research offers a deeper understanding of the complexities of gene expression and reproduction. While the idea of creating humans with two fathers remains far off, the study lays the groundwork for future breakthroughs in gene editing, fertility treatments, and stem cell biology, though it also raises important questions about the future of genetic engineering.
