News | Mice with two genetic fathers produce offspring—a major reproductive genetics breakthrough still far from human use
A study published in Proceedings of the National Academy of Sciences (PNAS) has drawn wide attention: for the first time, mice carrying genetic material from “two fathers” not only survived but also produced healthy offspring. The achievement is considered an important step toward same-sex genetic reproduction, although researchers emphasize that clinical use remains very distant.
Researchers at Shanghai Jiao Tong University created embryos containing only paternal genetic information by introducing two sperm cells into an egg whose nucleus had been removed. Because normal mammalian development depends on genetic “imprints” from both parents, the process faced major technical barriers.
Key breakthrough: epigenetic reprogramming overcomes the “imprinting barrier”
Using epigenome editing, the team reprogrammed seven key sites in sperm DNA, enabling embryos that otherwise could not develop to grow. Unlike conventional gene editing, the method does not alter the DNA sequence; it regulates gene “switches” to correct imbalanced paternal gene expression.
Of 259 embryos transferred into surrogate mice, only 2 male mice survived to adulthood, an extremely low success rate. More importantly, both produced offspring with normal appearance and physical characteristics after mating with females, demonstrating full reproductive capacity.
Why are “two fathers” so difficult?
Mice with two genetic mothers were created as early as 2004, including the well-known “Kaguya” mouse. Two-father reproduction is more challenging because of genomic imprinting.
During sperm and egg formation, chromosomes acquire different chemical marks that determine whether certain genes are active or inactive. Without either the maternal or paternal contribution, this balance is disrupted, potentially causing key genes to be doubly silenced or doubly activated and preventing embryonic development.
By precisely regulating these epigenetic marks, the study partially restored this balance without directly altering DNA.
Technical potential and practical limitations
The result supports a longstanding hypothesis that genomic imprinting is the main barrier to mammalian “single-parent reproduction” and that the barrier may be technically surmountable.
However, experts note that the technology is currently far from suitable for human use:
Extremely low success rate (only 2 of 259 embryos)
Requires many eggs and surrogates
Potential off-target risks from epigenetic regulation
Humans may require regulation of more numerous and complex sites
University College London researchers said the work “demonstrates that imprinting is indeed the main barrier and shows that it can be overcome,” while stressing that clinical translation remains infeasible.
Even if achieved in the future, individuals born through this method would still contain mitochondrial DNA from the egg donor and would therefore, strictly speaking, have “three-parent inheritance.”
Future direction: from basic mechanisms to reproductive medicine
Although clinical use remains distant, the study has important implications for basic science and reproductive medicine:
Deeper understanding of genomic imprinting
New models for infertility research
Advancement of epigenetic editing
A theoretical path toward same-sex genetic reproduction
Researchers plan to explore regulation of additional key sites and improve embryo development success rates to further assess the approach.
News | Mice with two genetic fathers produce offspring—a major reproductive genetics breakthrough still far from human use
News | Mice with two genetic fathers produce offspring—a major reproductive genetics breakthrough still far from human use
A study published in Proceedings of the National Academy of Sciences (PNAS) has drawn wide attention: for the first time, mice carrying genetic material from “two fathers” not only survived but also produced healthy offspring. The achievement is considered an important step toward same-sex genetic reproduction, although researchers emphasize that clinical use remains very distant.
Researchers at Shanghai Jiao Tong University created embryos containing only paternal genetic information by introducing two sperm cells into an egg whose nucleus had been removed. Because normal mammalian development depends on genetic “imprints” from both parents, the process faced major technical barriers.
Key breakthrough: epigenetic reprogramming overcomes the “imprinting barrier”
Using epigenome editing, the team reprogrammed seven key sites in sperm DNA, enabling embryos that otherwise could not develop to grow. Unlike conventional gene editing, the method does not alter the DNA sequence; it regulates gene “switches” to correct imbalanced paternal gene expression.
Of 259 embryos transferred into surrogate mice, only 2 male mice survived to adulthood, an extremely low success rate. More importantly, both produced offspring with normal appearance and physical characteristics after mating with females, demonstrating full reproductive capacity.
Why are “two fathers” so difficult?
Mice with two genetic mothers were created as early as 2004, including the well-known “Kaguya” mouse. Two-father reproduction is more challenging because of genomic imprinting.
During sperm and egg formation, chromosomes acquire different chemical marks that determine whether certain genes are active or inactive. Without either the maternal or paternal contribution, this balance is disrupted, potentially causing key genes to be doubly silenced or doubly activated and preventing embryonic development.
By precisely regulating these epigenetic marks, the study partially restored this balance without directly altering DNA.
Technical potential and practical limitations
The result supports a longstanding hypothesis that genomic imprinting is the main barrier to mammalian “single-parent reproduction” and that the barrier may be technically surmountable.
However, experts note that the technology is currently far from suitable for human use:
Extremely low success rate (only 2 of 259 embryos)
Requires many eggs and surrogates
Potential off-target risks from epigenetic regulation
Humans may require regulation of more numerous and complex sites
University College London researchers said the work “demonstrates that imprinting is indeed the main barrier and shows that it can be overcome,” while stressing that clinical translation remains infeasible.
Even if achieved in the future, individuals born through this method would still contain mitochondrial DNA from the egg donor and would therefore, strictly speaking, have “three-parent inheritance.”
Future direction: from basic mechanisms to reproductive medicine
Although clinical use remains distant, the study has important implications for basic science and reproductive medicine:
Deeper understanding of genomic imprinting
New models for infertility research
Advancement of epigenetic editing
A theoretical path toward same-sex genetic reproduction
Researchers plan to explore regulation of additional key sites and improve embryo development success rates to further assess the approach.
Story source:
Collected online