Antonios Frantzeskos

Culturing human embryos beyond day 13. Could we? Should we?

A sperm cell fusing its genetic material with an ovum to form a zygote is referred to as
fertilization. This is the first stage of human embryogenesis, the earliest stage of human
development. Embryogenesis defines a series of consequential processes including cleavage,
blastulation, gastrulation and a final stage organogenesis, which lead to the growth and
differentiation of the zygote for the first eight weeks. After the final stage, organogenesis, the
embryo is then considered a fetus.

The development of human embryos in the lab has proven to be a complicated task, with many
variables needed to be accounted for. Scientists have recently managed to develop human
embryos in vitro for 13 days. At this point, the embryo is ready for gastrulation. However,
embryo development most commonly halted at day 7. The significance of day 7 is that the
embryo, at this stage a blastocyst, is ready for implantation, which naturally occurs in the uterine
endometrium. Reproducing similar conditions for the embryo after day 7 in the lab had been a
great challenge. A couple of years ago a new technique tested in mice has now proven to be
successful in human embryo culturing post implantation stage. Blastocysts between days 5 to 7
were firstly placed in a specially designed in vitro culture medium for 2 days which was
sequentially substituted for a different medium, both containing a variety of nutrients and
hormones. Attachment of the embryo to the dish and subsequently the embryos growth was
observed up until day 13. At this stage the experiment was stopped due to a law stating that,
embryos may be cultured only up to day 14, due to the primitive streak being developed around
this time. At this point the embryo is considered to have gained its individuality since, after
developing the primitive streak there is no chance it will split into twins. The potential to go
further than 13 days is there. Further tweaking of the gel matrix in the dish as well as the culture
medium components embryos could be cultured further than day 13.

For now scientists are focusing on the valuable extra days of development they have the
potential to research. The time period from day 7 to 13 will provide insight into the preparation of
the blastocyte for gastrulation in this post implantation phase. Embryos are immunostained at
various time points and studied for morphological and cell marker changes, providing crucial
information on cell fate during this period. For example OCT4 from the epiblast and GATA6 from
the hypoblast are observed to follow the fate of these cell types in the blastocyst.
 Antonios Frantzeskos

This breakthrough will provide important knowledge on human development. It is becoming

clearer that animal models, for human embryogenesis are not very accurate. With increasing
number of cells seen at post implantation stage, there is a wider range of possible cell fates and
organization animal models cannot predict. Moreover it will give greater insight into a number of
embryonic disorders, reasons for early miscarriages and deciding on the viability of embryos
used in IVF. Furthermore these embryo cultures could be used in toxicology tests.

There currently is a law preventing any attempts to develop embryos beyond the formation of
the primitive streak, for the reasons mentioned above it would be of great clinical significance.
However the first question to ask is who decides at what stage this embryo is considered
human? Moreover it is not certain that the in vitro experiments represent the in vivo. For the
time being there is no rush to change the law as there is a lot to be learned in the post
implantation period.

Antonios Frantzeskos