HEALTHY MICE WITH

SAME-SEX PARENTS BORN

FOR FIRST TIME
M. Septian Wahyu P.
XII IPS 3/20
Healthy mice with two mothers have been born for the first time in a study that pushes
the boundaries of reproductive science.
Mice with two fathers were also born, but only survived a couple of days, the Chinese
team behind the work reported. There is no imminent prospect of the techniques being
used clinically in people, but the findings demonstrate that the biological barriers to
same-sex reproduction can, technically, be overcome.
Scientists have previously managed to produce baby mice with same-sex parents, but the
offspring had serious abnormalities and the methods used often required convoluted
sequences of genetic manipulations, sometimes involving several generations of mice. The
work explores a long-standing question in biology: that of why in mammals, equal genetic
contributions from both a mother and a father are necessary. Elsewhere in the animal
kingdom – in hammerhead sharks and komodo dragons, for instance – no genetic
contribution from a father is required.
A major barrier in mammals is a phenomenon known as “imprinting”, where for 100 or so
genes only the copy that came from the mother or only the copy that came from the father
are ever switched on. In the genome, maternal and paternal contributions are all jumbled
together but these genes carry a chemical tag, labelling which parent the gene originated
from in the first place.
Without the right pattern of male and female imprinting, a viable embryo cannot be
produced.
The latest paper demonstrates how this apparent barrier could be overcome. For the
mice with two mothers, the scientists started off with embryonic stem cells from a
female mouse. Using the gene-editing tool Crispr-Cas9, they were able to remove
maternal imprinting from three crucial regions of DNA by snipping out a single letter of
the genetic code where the chemical tag was attached. This effectively made the
genetic material appear more “male” in terms of its imprinting pattern.
When the modified stem cells were injected into the unfertilised egg of a second female mouse, the
genetic material from the two female mice combined to form an embryo.
They produced 29 live mice from 210 embryos. The mice were normal, lived to adulthood and had
babies of their own. A similar experiment was performed using sperm and genetically modified stem
cells from a male mouse, which were injected into a female egg that had been stripped of its own
genetic material. These embryos were transferred to surrogate mothers, who carried them to term. But
the pups only survived 48 hours after birth.
There is good evidence that imprinting plays a similar role in human reproduction, although involving
some different genes. However, there is no prospect of this strategy being applied in the clinic as there
would be serious concerns about the side-effects of modifying genes which are known to be crucial
for basic development.
“It is unthinkable to generate a human baby that way,” said Christopher Galichet,
senior scientist, at The Francis Crick Institute in London. “The authors have made an
extremely important step forward in understanding why mammals can only reproduce
sexually,” he added.
Prof Azim Surani, director of germline and epigenomics research at the Gurdon
Institute, University of Cambridge, said: “The comprehensive nature of the
manipulations involved rules out – at least for now – any such attempts to generate bi-
maternal human embryos. The bi-paternal embryos in this experiment, in any case, did
not survive for long”.
ANY QUESTION?