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Why is human reproduction such a challenge?

A new study by a researcher at the Milner Centre for Evolution at the University of Bath contends that "selfish chromosomes" are to blame for the early demise of the majority of human embryos. 

The discovery that explains why human embryos frequently don’t survive while fish embryos do not has repercussions for the management of infertility. It was published in PLoS Biology.

Before a woman even realises she is pregnant, over half of fertilised eggs experience a very early death. After a few weeks, many pregnancies that do live to be recognised as such spontaneously end. Such miscarriages are shockingly frequent and extremely upsetting.

The Milner Centre for Evolution’s Director, Professor Laurence Hurst, looked into why it’s still challenging for humans to bear children.

The incorrect number of chromosomes in the embryos is the direct cause of many of these early fatalities.

46 chromosomes should be present in fertilised eggs, 23 from the mother and 23 from the father. According to Professor Hurst, practically every embryo with the incorrect number of chromosomes—often 45 or 47—dies in the womb. About 80% of unfortunate cases, including Down syndrome with three copies of chromosome 21, will not survive to term.

Hurst put up a variety of hints.

First of all, faults occurred when the mother makes the eggs, not when the father makes the sperm, are typically to blame for the embryo having the incorrect number of chromosomes. In actuality, there are too few chromosomes in more than 70% of produced eggs.

Second, the errors occur during the first of the two processes in the production of eggs. The partner chromosome must be destroyed in order to complete the first stage since mutations that impede the process can “selfishly” infiltrate more than 50% of the eggs. This has been long suspected in humans and is thoroughly investigated in mice.

Hurst discovered that a selfish mutation in animals that tries to do this but fails, producing an egg with either too many or too few chromosomes, can nonetheless lead to better off offspring in terms of evolution. In animals, when the mother nourishes the developing foetus continually in the womb, it is advantageous evolutionarily for embryos created from defective eggs to be lost sooner rather than carried to term. This indicates that the descendants who survive do better than average.

Hurst outlined how a pair of chromosomes will have one go to the egg while the other is destroyed. However, if a chromosome “knows” it will be destroyed, it essentially has nothing to lose. Remarkable recent molecular research has revealed that certain chromosomes change their behaviour to avoid being destroyed when they sense that they are about to be destroyed during this initial step. This behaviour could result in chromosome loss or gain as well as the death of the embryo. What’s amazing is that the mutation is better off since it kills embryos if it benefits the other children of that mother, as the selfish chromosome will frequently be in the siblings and sisters who get the additional nourishment.

Hurst believes that people might actually be particularly vulnerable. When an embryo in a mouse brood dies, the survivors receive resources. This increases the likelihood that the others will survive by around 10%. Humans, on the other hand, often only have one child at a time, and the early death of an embryo allows a mother to quickly have another child — she likely had no idea that her egg had been fertilised.

According to preliminary evidence, mammals that only have one embryo at a time, like cows, appear to have very high rates of embryo death caused by chromosomal abnormalities, whereas mammals that have several embryos in a brood, like mice and pigs, appear to have relatively lower rates.

According to Hurst’s findings, low amounts of a protein called Bub1 may also be responsible for chromosomal increase or loss in humans.

Hurst said: “The levels of Bub1 go down as mothers get older and as the rate of embryonic chromosomal problems goes up. Identifying these suppressor proteins and increasing their level in older mothers could restore fertility. I would hope too that these insights will be one step to helping those women who experience difficulties getting pregnant, or suffer recurrent miscarriage.”

Why is human reproduction such a challenge?

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