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'Hairy embryos'. What is a hair protein doing in an embryo?

The journal, “Nature”, is a big deal in scientific literature, and so when it publishes a paper on early embryo development (a rare occurrence), you know it’s something quite significant.

A recent issue (https://doi.org/10.1038/s41586-020-2647-4) featured a publication that described not only the presence of a “hair, nail and hoof” protein within the embryo, but provided an explanation why it was there.

Keratins are proteins that provide the structural strength to hair and nails. You may have seen some shampoo advertising claiming keratin in their formulation. Keratins are not necessarily found in all cells, but there are other cells that have these proteins, most commonly the cells that line the surfaces of organs, acting as the transition layer of cells from “the outside” to inside an organ. Keratins effectively toughens these cells.

And this is where keratins becomes important to embryo development. Embryos start as a fertilised egg and begin to divide. These new cells are smaller versions of the fertilised egg. But after about 3 rounds of cell division, when the embryo has 8-cells, things change – they begin to organise themselves, eventually forming two types of cells: the trophoblast (the outer cells, which go on to form the placenta) and the inner cell mass cells (which go on to form the fetus, and a little of the placenta). The result is what is called a blastocyst-stage embryo, pictured below, and containing usually over 100 cells.

All sorts of theories abound about how mammalian embryos determined which cells were destined to be trophectoderm. It did seem that cells that were more on the ‘outside’ surface, were more disposed to become trophectoderm, but it wasn’t always the case. This paper ‘nailed it’ (excuse the pun!). After the 3rd round of divisions, some of the cells that were on the ‘outside’ not only produced keratin, but made sure that when it divided, the keratin was always in the new cell that had the ‘outside’ orientation. This would continue to form the blastocyst. How the keratin stays on outer side of the dividing cell appears to involve another structural protein, actin. But it’s the accumulation of keratin in the newly divided outer cell that is the important event.

Will this change how we practice clinical IVF? It’s hard to say just now. It may bring more focus on culture medium formulation that support keratin formation, or the use of cellular keratin markers to explain why some embryos don’t grow to the blastocyst stage. For example, what does aneuploidy (differences in chromosome number between embryonic cells) do to keratin production and accumulation?

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