Why is it so hard for people to have a baby?

embryo

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New research from a scientist at the Milner Center for Evolution at the University of Bath suggests that “selfish chromosomes” explain why most human embryos die at a very young age. The study, published in PLoS biologywhich explains why fish embryos are fine but unfortunately human embryos often don’t survive, has implications for infertility treatment.

About half of the fertilized eggs die very early, before a mother even knows she is pregnant. Tragically, many of those who survive to become a recognized pregnancy abort spontaneously after a few weeks. Such miscarriages are both remarkably common and very distressing.

Professor Laurence Hurst, director of the Milner Center for Evolution, investigated why, despite hundreds of thousands of years of evolution, it is still comparatively difficult for humans to have a baby.

The proximate cause of many of these early deaths is that the embryos have the wrong number of chromosomes. Fertilized eggs should have 46 chromosomes, 23 from the mother in the eggs, 23 from the father in the sperm.

Professor Hurst said: “A great many embryos have the wrong number of chromosomes, often 45 or 47, and almost all of them die in the womb. Unfortunately, even in cases like Down syndrome with three copies of chromosome 21, about 80% will not make it to the end.”

Why should gaining or losing a chromosome be so common when it is so deadly?

There are a number of clues Hurst has compiled. First, if the embryo has the wrong number of chromosomes, it’s usually due to errors that occur in the mother’s egg formation, not the father’s sperm formation. In fact, over 70% of eggs produced have the wrong number of chromosomes.

Second, the mistakes happen in the first of two steps in making eggs. This first step, as previously noted, is susceptible to mutations that disrupt the process, so the mutation can “self-interestedly” creep into more than 50% of the oocytes, forcing the destruction of the partner chromosome, a process known as is centromeric drive. This is well studied in mice, has long been suspected in humans, and was previously thought to be somehow related to the problem of chromosome loss or gain.

What Hurst noted was that in mammals, a selfish mutation that tries but fails, resulting in an egg with one too many or one too few chromosomes, may still be better off evolutionarily. Because the mother continuously nourishes the developing fetus in the womb, it is evolutionarily advantageous in mammals that embryos developing from defective eggs are lost sooner rather than being carried to term. This means that the surviving offspring will do better than average.

Hurst explained, “That first step of making eggs is weird. One chromosome of a pair goes into the egg, the other is destroyed. But if a chromosome ‘knows’ that it is being destroyed, it has nothing to lose. Remarkable recent molecular evidence has revealed that when some chromosomes realize they are being destroyed during this first step, they change tack to prevent that they are destroyed, possibly causing chromosome loss or gain and death of the embryo.

“What’s remarkable is that if the death of the embryo benefits that mother’s other offspring, since the selfish chromosome is often in the brothers and sisters who get the extra nourishment, the mutation is better off because it kills embryos.”

“Fish and amphibians don’t have this problem,” Hurst commented. “In over 2000 fish embryos, not a single one with chromosomal defects from the mother was found”. Rates in birds are also very low, about 1/25th the rate in mammals. This, Hurst notes, is also predictable since there is some competition between nestlings after they hatch but not before.

In contrast, chromosome loss or gain is a problem for every mammal studied. Hurst commented, “It is a disadvantage to nurture our offspring in the womb. If they die early, the survivors benefit. It makes us vulnerable to that kind of mutation.”

Hurst suspects that humans are actually particularly vulnerable. In mice, the death of an embryo gives resources to survivors in the same brood. This increases the others’ chances of surviving by about 10%. However, humans normally only have one baby at a time, and the early death of an embryo allows a mother to reproduce quickly—she probably didn’t even know her egg was fertilized.

Preliminary data show that mammals such as cows with one embryo at a time appear to have particularly high rates of embryo mortality due to chromosomal defects, while those with many embryos in a brood such as mice and pigs appear to have slightly lower rates.

Hurst’s research also suggests that low levels of a protein called Bub1 can lead to the loss or gain of a chromosome in both humans and mice.

Hurst said: “Bub1 levels decrease as mothers get older and the rate of embryonic chromosomal problems increases. Identifying these suppressor proteins and increasing their levels in older mothers could restore fertility.

“I also hope that these findings are a step toward helping women who are struggling to conceive or who are experiencing recurrent miscarriages.”


Chromosomal defects that develop early lead to embryonic loss in assisted reproductive technology


More information:
Selfish centromeres and the waste of human reproduction, PLoS biology (2022). DOI: 10.1371/journal.pbio.3001671

Provided by the University of Bath

Citation: Why is it so hard for people to have a baby? (2022, July 5) Retrieved July 5, 2022 from https://phys.org/news/2022-07-hard-humans-baby.html

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