Saturday, 13 December 2014

Molecular Inactivation and the role of PTHrP

by Maharshi Chakravortee

Ever wondered why male Homo sapiens have nipples on their chest? Are they vestigial like the appendix, the wisdom teeth or body hair? Or they’re just present for weird piercings or to taunt hungry infants? Well, the answer is quite interesting. Turns out, human males have nipples because at some point of the embryonic stage, we were all girls. Yeah, you heard me tough guy!

Unlike the other vestigial organs, nipples aren’t those organs that are just left overs from any evolutionary event where male humans used to breast feed, at any point in the course of evolution male humans did not have mammary glands to do so. So the evidential fact that male humans have nipples is kind of flattering.  With that in mind, male mice are the only mammals that do not have nipples, so one might think they’re probably tougher than us guys! Thus the question still remains, why do males have them?

The human gestation period goes from zygote, to embryo, to foetus and then to a baby, which is either a male or a female. As the sex of a baby is determined whether one chromosome from the dad is either an X or a Y, what’s interesting to know that all human embryo’s start off with a female blueprint, i.e. presuming to have two X chromosomes. (Yes, we were all girls at one point of our life).  Up until the sex is determined (activation of the Y chromosome), the process of a typical female embryo development is already started. Within the first several weeks, pair of ‘milk ridges’ or milk lines form on every embryo, either male or a female, which serves as the foundational mammary tissue for the development of nipples and mammary organs.  After the sex is determined, i.e. one of the sex chromosomes becomes a Y, a protein called PHTrP is synthesised which causes the embryo to develop male hormone receptors. 

Thus, those male hormones that bind to the PTHrP produced receptors effectively destroy the mammary tissues, but interestingly fail to disintegrate the already formed nipples. This is because the PTHrP synthesis in human embryonic stage is actually quite late, thus giving male and females similar internal structures in the breast region. However one might note that male mice do not have nipples, due to their PTHrP signals are quite fast, according to a 1999 Yale University Research.  Thus it could be said that male nipples are just genetic by-products of female breasts.

In the sex determination process, two X chromosomes make a female, and an X and a Y make a male. What’s of vital importance is that since males have different chromosomes, both can remain active for the rest of the life. However females have a pair of similar chromosomes, and one of them needs to be inactivated in order for proper development to occur.

When a female embryo is in a 100-celled blastocyst stage, the two chromosomes in every cell undergo a tiny molecular battle, which silences any one of the X chromosomes, either from mum or from dad. This is done by packing one of two chromosomes in such a way that it cannot be read. This un-readable from of DNA is called a Barr body. Extreme close packing of DNA by histone protein tails and addition of methyl groups, which makes it impossible for RNA polymerase to transcribe it, thus not coding for any protein makes that Barr body structure.

It is interesting to know that in that 100-celled female embryo, it is of random chance that which chromosome is silenced, either the one from the mum, or the one from the dad.  Thus this 100-celled embryo ends up with a mixture of active X chromosomes, and from this point forward as these cells divide, they maintain the active X chromosome that they had inside. Thus the cells with dads active X chromosomes further give rise to the similar type of cells with dads active X chromosomes, and same with the cells having active X chromosomes from the mom.  And this continues into adulthood.

This can be very nicely seen in Calico cats, that’s because the gene for coat color is on the X chromosome. Just by looking at the pattern of their different colored spots, it can be seen where the mums or dads X chromosome has been inactivated.  And this also shows that only female cats can be Calico cats, because only female cats can inherit two X chromosomes, thus having two color genes.




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