News | Selfish Chromosomes May Be Driving Early Pregnancy Loss
Why are human embryos so vulnerable? Why do so many embryos die within the first few days despite successful fertilization, often before pregnancy is recognized? Research from the Milner Centre for Evolution at the University of Bath in the United Kingdom offers a new explanation: selfish conflict between chromosomes may be responsible.
The study was led by Professor Laurence Hurst, director of the center and an evolutionary geneticist, and published in PLOS Biology. He noted that approximately half of human fertilized eggs die at a very early stage, often before pregnancy is recognized. Even after a detectable pregnancy is established, many embryos are lost through miscarriage within several weeks.
Incorrect Chromosome Numbers Are a Major Hidden Cause
Professor Hurst noted that abnormal chromosome numbers are the direct cause of most early embryo deaths. Normal human cells have 46 chromosomes: 23 from the mother's egg and 23 from the father's sperm. Many embryos do not have this standard number and may have only 45 or as many as 47 chromosomes, leading to loss during pregnancy.
Even among detectable chromosome abnormalities, such as Down syndrome, which involves three copies of chromosome 21, approximately 80% of affected embryos do not survive to term.
Given that chromosome abnormalities can be so serious, why do they occur so frequently?
Selfish Chromosomes: A Hidden Driver of Embryo Loss
Professor Hurst said the key lies in egg formation. He found that most errors in chromosome number originate during the first stage of maternal egg formation rather than during sperm production. Research suggests that more than 70% of eggs already have the wrong number of chromosomes during formation.
This first stage is also when selfish chromosomes may interfere. A mechanism called centromeric drive allows certain selfish chromosomes to disrupt competing chromosomes and force their way into more eggs, increasing their chance of inheritance. In other words, they eliminate the chromosome that should be paired with them to improve their representation in the next generation.
This chromosomal conflict has been studied in animals such as mice, and a similar mechanism has previously been suspected in humans. Hurst's research is the first to closely link it to early embryo mortality.
He further noted that even if these selfish chromosomes fail to drive successfully and produce an abnormal chromosome number, either one extra or one missing, they may still gain an evolutionary advantage.
Sacrificing One to Benefit Others: A Harsh Evolutionary Strategy
In humans and other mammals, embryos develop inside the mother and require a continuous supply of nutrients. If an embryo dies very early, the mother can enter another reproductive cycle sooner without expending additional resources. This mechanism may benefit surviving siblings.
Hurst explained, "If a selfish chromosome 'knows' it is about to be eliminated, it may use unconventional tactics to disrupt cell division and preserve itself. But this may prevent the embryo from developing and ultimately cause its death."
More surprisingly, the mechanism is not widespread across all animals. Hurst noted that researchers found no maternally derived chromosome errors in a study of more than 2,000 fish embryos. Such problems are also rare in birds, where chromosome abnormalities occur at only 1/25 the rate seen in mammals. This may be related to when competition for resources occurs: mammalian embryos compete inside the uterus, while birds and fish compete after hatching.
A Consequence of a Reproductive Strategy
Professor Hurst concluded that high embryo mortality is a byproduct of competition among mammals. "The cost of this mechanism is that we become especially vulnerable to the effects of chromosome mutations."
Preliminary data show particularly high embryo mortality among mammals that usually carry one embryo per pregnancy, such as humans and cattle, while species that carry multiple offspring, such as mice and pigs, have slightly lower mortality. This also supports a resource redistribution effect, in which embryos that die leave more nutrients and space for their littermates.
Hurst also noted that low levels of a protein called Bub1 may directly cause chromosome loss or gain. He added, "Bub1 levels decline as maternal age increases, and the likelihood of chromosome abnormalities in embryos rises accordingly. Increasing this protein may potentially help restore fertility in older women."
He expressed hope that the study would provide new directions for addressing infertility and recurrent miscarriage.
News | Selfish Chromosomes May Be Driving Early Pregnancy Loss
News | Selfish Chromosomes May Be Driving Early Pregnancy Loss
Why are human embryos so vulnerable? Why do so many embryos die within the first few days despite successful fertilization, often before pregnancy is recognized? Research from the Milner Centre for Evolution at the University of Bath in the United Kingdom offers a new explanation: selfish conflict between chromosomes may be responsible.
The study was led by Professor Laurence Hurst, director of the center and an evolutionary geneticist, and published in PLOS Biology. He noted that approximately half of human fertilized eggs die at a very early stage, often before pregnancy is recognized. Even after a detectable pregnancy is established, many embryos are lost through miscarriage within several weeks.
Incorrect Chromosome Numbers Are a Major Hidden Cause
Professor Hurst noted that abnormal chromosome numbers are the direct cause of most early embryo deaths. Normal human cells have 46 chromosomes: 23 from the mother's egg and 23 from the father's sperm. Many embryos do not have this standard number and may have only 45 or as many as 47 chromosomes, leading to loss during pregnancy.
Even among detectable chromosome abnormalities, such as Down syndrome, which involves three copies of chromosome 21, approximately 80% of affected embryos do not survive to term.
Given that chromosome abnormalities can be so serious, why do they occur so frequently?
Selfish Chromosomes: A Hidden Driver of Embryo Loss
Professor Hurst said the key lies in egg formation. He found that most errors in chromosome number originate during the first stage of maternal egg formation rather than during sperm production. Research suggests that more than 70% of eggs already have the wrong number of chromosomes during formation.
This first stage is also when selfish chromosomes may interfere. A mechanism called centromeric drive allows certain selfish chromosomes to disrupt competing chromosomes and force their way into more eggs, increasing their chance of inheritance. In other words, they eliminate the chromosome that should be paired with them to improve their representation in the next generation.
This chromosomal conflict has been studied in animals such as mice, and a similar mechanism has previously been suspected in humans. Hurst's research is the first to closely link it to early embryo mortality.
He further noted that even if these selfish chromosomes fail to drive successfully and produce an abnormal chromosome number, either one extra or one missing, they may still gain an evolutionary advantage.
Sacrificing One to Benefit Others: A Harsh Evolutionary Strategy
In humans and other mammals, embryos develop inside the mother and require a continuous supply of nutrients. If an embryo dies very early, the mother can enter another reproductive cycle sooner without expending additional resources. This mechanism may benefit surviving siblings.
Hurst explained, "If a selfish chromosome 'knows' it is about to be eliminated, it may use unconventional tactics to disrupt cell division and preserve itself. But this may prevent the embryo from developing and ultimately cause its death."
More surprisingly, the mechanism is not widespread across all animals. Hurst noted that researchers found no maternally derived chromosome errors in a study of more than 2,000 fish embryos. Such problems are also rare in birds, where chromosome abnormalities occur at only 1/25 the rate seen in mammals. This may be related to when competition for resources occurs: mammalian embryos compete inside the uterus, while birds and fish compete after hatching.
A Consequence of a Reproductive Strategy
Professor Hurst concluded that high embryo mortality is a byproduct of competition among mammals. "The cost of this mechanism is that we become especially vulnerable to the effects of chromosome mutations."
Preliminary data show particularly high embryo mortality among mammals that usually carry one embryo per pregnancy, such as humans and cattle, while species that carry multiple offspring, such as mice and pigs, have slightly lower mortality. This also supports a resource redistribution effect, in which embryos that die leave more nutrients and space for their littermates.
Hurst also noted that low levels of a protein called Bub1 may directly cause chromosome loss or gain. He added, "Bub1 levels decline as maternal age increases, and the likelihood of chromosome abnormalities in embryos rises accordingly. Increasing this protein may potentially help restore fertility in older women."
He expressed hope that the study would provide new directions for addressing infertility and recurrent miscarriage.
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