Summary: Researchers have successfully engineered bi-paternal animals, born from two female relatives, that survived to adulthood using embryonic stem cell methods. By modifying 20 important imprinting genes, they overcame the evolutionary obstacles that had previously prevented monoecious reproduction in animals.
The findings highlight imprinted defects as a big obstacle to vertebrate unisexual reproduction, even though only 11.8 % of eggs have matured to the point where they were. The study advances regenerative treatments, providing insights into imprinting-related illnesses, but social and technical difficulties still exist for extending this function to larger animals or humans.
Important Facts:
- Breakthrough Technique: Editing 20 etching genes enabled bi-paternal rabbits to live to age.
- Developmental Limitations: Just 11.8 % of embryos reached delivery, with several exhibiting problems.
- Coming Objectives: Scientists want to expand their findings to more powerful animals and improve outcomes.
Origin: Cell Press
A group of plant cell scientists properly used embryonic stem cell engineering to create a bi-paternal mouse, a mouse with two adult parents, that lived until adulthood.
Their findings, which were published on January 28, 2025, in the Cell Press journal Cell Stem Cell, explain how the researchers were able to overcome recently unsolvable difficulties in unisexual duplication in mammals by targeting a specific set of genes involved in duplication.  ,
Before, bi-paternal animals had been tried by scientists, but the embryos just developed for a short while before stopping growing.
Here, the investigators, led by corresponding author Wei Li of the Chinese Academy of Sciences ( CAS ) in Beijing, focused on targeting imprinting genes, which regulate gene expression in a number of ways.
This study will help to overcome a number of research gaps in stem cell and restorative treatments, Li claims.  ,
According to co-author Qi Zhou, even a co-author of the CAS,” the distinctive characteristics of imprinting genes have led scientists to think that they are a fundamental challenge to monoecious reproduction in mammals.”
” Even when constructing bi-maternal or bi-paternal embryos artificially, they fail to develop properly, and they stall at some point during development due to these genes” . ,
Oocytes from adult embryonic stem cells were previously fertilized with eggs from another man in preparation for a bi-paternal mouse.
However, when the identical chromosomes—the chromosomes that separate during mitosis to create oocytes and sperm—originated from the same gender, imprinting defects arose, leading to severe developmental problems.  ,  ,
In this study, the analysts modified 20 major etching alleles individually using a number of different methods, including frameshift mutations, protein deletions, and governmental area edits.
They discovered that these edits resulted in the development of stem cells with more robust pluripotency in addition to allowing the development of bi-paternal animals that occasionally lived to adulthood.  ,
According to co-author Guan-Zheng Luo of Sun Yat-sen University in Guangzhou,” These results provide strong proof that imprinting defects are the main hurdle to mammal monoecious reproduction.”
This method has the potential to significantly improve the development outcomes of cloned and embryonic stem cells, paving a promising path for the development of regenerative medicine.
The researchers point out a number of limitations that their work still needs to be addressed. For one thing, only 11.8 % of the stillborn embryos were able to develop up until the day of birth, and not all of the born-born babies were able to reach adulthood as a result of developmental problems.
Most of those who did reach adulthood had stunted growth and lived shorter lives. Also, the mice that lived to adulthood were sterile, although they did exhibit increased cloning efficiency.  ,  ,
According to co-author Zhi-Kun Li of CAS, “further modifications to the imprinting genes could lead to the generation of healthy bi-paternal mice capable of producing viable gametes and develop novel therapeutic approaches for imprinting-related diseases.”  ,
The team will continue to research how changing imprinting genes might result in embryos with higher developmental potential. Additionally, they want to apply the research done in mice to larger animals, including monkeys.
They point out that this will require a lot of time and effort because monkeys ‘ imprinting gene combinations are significantly different from those in mice.
It’s unclear whether this technology will ultimately be used to treat human diseases. Because they are currently deemed unsafe, the International Society for Stem Cell Research’s ethical guidelines for stem cell research forbid heritable genome editing for reproductive purposes as well as the use of human stem cell-derived gametes for reproduction.  ,
About this news about research being done on genetic engineering and reproduction
Author: Kristopher Benke
Source: Cell Press
Contact: Kristopher Benke – Cell Press
Image: The image is credited to Neuroscience News
Original Research: Open access.
Wei Li et al.,” Adult bi-paternal offspring produced through direct modification of imprinted genes in mammals.” Cell Stem Cell
Abstract
Adult bi-paternal offspring are produced by direct modification of imprinted genes in mammals.
With no universal correction method for applications involving embryonic stem cells, induced pluripotent stem cells, and animal cloning, their complexity and stochastic nature pose a significant challenge in applications involving embryonic stem cells, induced pluripotent stem cells, and cloning.
In this study, we targeted these defects at their source—embryos from same-sex parents —aiming to establish a stable, maintainable imprinting pattern , de novo , in mammalian cells.
Using bi-paternal mouse embryos, which exhibit severe imprinting defects and are typically non-viable, we introduced frameshift mutations, gene deletions, and regulatory edits at 20 key imprinted loci, ultimately achieving the development of fully adult animals, albeit with a relatively low survival rate.
The findings provide compelling proof that mammals ‘ imprinting abnormalities are their main obstacle to unisexual reproduction.
Additionally, this approach has the potential to significantly improve the development of cloned and embryonic stem cells, opening up new frontiers for regenerative medicine.
