Building a baby: The first two weeks

This is how a human gets made. Every one of us started out this way. We have a pretty good idea what happens over the 9 months it takes to produce a newborn, but there’s this one bit that’s been missing. Right at the beginning, before this animation even starts – the very first few weeks. Now, armed with new ways of growing human embryos in the lab, scientists are learning what the very beginning of human development looks like. For decades, studying this crucial, early time in a human embryo’s development was a technical headache – embryos are hard to get and keep alive outside the body. And it’s an ethical challenge. Guidelines put together in the late 70s and 80s prevent scientists from growing embryos for longer than 14 days. Despite the hurdles, scientists do know a bit about what happens in those critical weeks – often from animal studies or rare human tissue samples. They know that sperm fertilises egg, and one cell grows to two, four, eight, and so on. Around day 5 or 6, the blob starts to feature different types of cell. Scientists call this blob a blastocyst. All being well, the cells in the blastocyst begin to differentiate. One week in, it implants into the wall of the uterus. What happens next has been a bit of a mystery: by implanting itself into the womb’s wall, the embryo basically hides, and that makes studying it in humans impossible. One way of exploring this crucial time, is to study embryos donated by people who no longer need them for fertility treatment. In the last few years, several labs have developed new ways to nurture these embryos. Their techniques have allowed them to start building a picture of human development that’s more detailed than ever before. Here’s a day 6 embryo growing in a lab. Cells destined to become the actual fetus are tagged in green, those that go on to form the placenta in blue. By day 8 the cells are sorting and arranging themselves – the green fetal cells have condensed together, and in red here are the cells that will form the interface between the baby and the placenta. It seems these ‘extra-embryonic’ structures develop a little later in humans than expected from studies in other animals. Day 10. The whole thing increases in size, and bundles of cells start developing into support structures. Surprisingly at this stage, the embryo can direct its own development, with no input from the mother’s tissues. By day 12, the outskirts of the embryo are preparing to bind more strongly to the wall of the uterus. After all, if this were a natural pregnancy, the embryo would be there for the next 9 months. You can even see little holes appearing ready for the mother’s blood vessels to start supplying the embryo with essential oxygen and nutrients. By now the embryo is signalling its presence to the mother via a hormone – the one that pregnancy tests pick up – HCG – labelled here in yellow. After two weeks, the teams ended their experiments in line with the ethical 14-day limit. To study what happens after 14 days, researchers had to turn to different techniques. Recently scientists have built artificial, embryo-like structures from stem cells. Using these partial models, they can study things like cell signalling, or even the formation of the primitive streak – the crucial thread of cells which guides the process called gastrulation. That’s the moment the embryo decides which end will become the head. Here they use human stem cells growing in an animal embryo to explore that process. But even after this early phase is over, there is still a lot of work involved in building a body. To study later phases, scientists have made and analysed high-resolution, 3D atlases of human embryos and fetuses. One team found that the left and rights hands don’t simply mirror each other when growing their nerves. Instead, some branches take random paths in each limb. Another group saw muscles that grew in early embryos, only to disappear as the fetus developed – like these. As yet, they’re not sure why. It’s becoming ever clearer just how important a human embryo’s first few weeks are. Many scientists hope that more research will lead to a better grasp of why some pregnancies fail, and how birth defects arise. Maybe even make in vitro fertilisation work better. But some just want to understand exactly what happens to this tiny ball of cells, in this short spark of time at the beginning of all of us.

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