Miscarriages are, sadly, very common. It's estimated that 10 to 15 percent of all pregnancies end in miscarriage, according to Healthline, though the number could be up to 50 percent. The organization March Of Dimes noted at WebMD that many miscarriages may take place before a person even knows they're pregnant, and may be mistaken for a typical period. They can be triggered by many different things, or seem to have no cause at all, but a new study in Nature has revealed an unusual potential cause: inflammation caused by the replication of faulty DNA.
Seeking the 'reason' behind a miscarriage can be traumatic, and for many women it can be impossible to know what happened. Genetics may play a role; the American College of Obstetricians and Gynecologists wrote around 50 percent of all miscarriages are caused by "chromosomal abnormalities," in which "the embryo receives an abnormal number of chromosomes." If you remember your high school biology, an embryo is formed when the sperm and egg combine their 23 sets of chromosomes each, producing 46. If in some way the number is off, chromosomal abnormalities result, which can mean the embryo stops developing and miscarriage happens.
We now have an insight into one particular way in which this might go awry in women. The study in Nature, which was performed on mice, found that miscarriages can be caused by faulty DNA replication. When the cells of a fertilized egg begin to divide and grow bigger, each cell has a replicated set of DNA inside. The process of DNA replication is complicated, but it's partly powered by something called the minichromosome maintenance complex, or MCM, which helps create the familiar double strands of DNA. The scientists behind the study in Nature found that when the MCM was damaged in mice, the DNA in their embryos failed to replicate properly.
In typical pregnancies, the body has to resist its standard immune system response. A study from Stanford in 2017 revealed that the immune system follows a strict "clock" during pregnancy; the immune system stops the body from rejecting the fetus, then changes throughout the pregnancy to try and protect both mother and fetus from outside threats. In mice whose DNA replication system was faulty, their bodies boosted inflammation levels and immune response. That inflammation increased the rate of miscarriage pretty dramatically in the form of the immune system was 'rejecting' the damaged embryos.
The scientists also found that female mice embryos were far more likely to miscarry from this particular kind of damaged DNA than male ones. The reason? Sarah Lambert, reviewing the science for Nature, explained: "This sex-biased embryonic death is caused by the inability of female embryos to produce testosterone, an anti-inflammatory hormone." Estrogen can increase inflammation in the body, while testosterone decreases it. Male embryos in the study were able to protect themselves despite having chromosomal abnormalities because of their testosterone levels, while female embryos didn't have that option.
More research needs to be done to see if this particular discovery — that faulty DNA replication causes miscarriages through inflammation, and particularly targets female embryos — holds true in humans. However, it's an interesting insight into the medical realities of a very hard, very common experience.