Getting pregnant and staying pregnant may come easy for some couples, but for others, it can seem like a difficult dream. Some women are susceptible to recurrent miscarriages, and experience two or more consecutive pregnancy losses in the first trimester. These women may feel shame or even guilt, but an international team of researchers suggests some miscarriages may be caused by genetics.  

Doctors have found half of miscarriages are tied to a specific issue, such as infections, hormonal balance, or immune problems. For the other half of losses, medical experts have not found an explanation. But, new research published in the Royal Society Journal Open Biology proposes this may be due to genetic mutations, specifically in the FOXD1 gene.

“We found that women with FOXD1 mutations have a statistically high risk of suffering RSA [recurrent spontaneous abortion],” wrote the team, in the study.

The gene belongs to the forkhead family of transcription factors, which play an important role in regulating gene expression in cell growth, proliferation, differentiation, and longevity, characterized by a distinct forkhead domin. The gene functions in kidney development by promoting nephron progenitor differentiation; nephron progenitor cells differentiate to form nephrons during embryonic kidney development. FOXD1 gene also functions in the development of the retina and optic chiasm. It may also regulate inflammatory reactions and prevent autoimmunity.

The mutation of this gene was first pinpointed in lab mice. Then, the researchers sought to examine whether over 550 women affected by RSA had mutations in the same gene. RSA is defined as the occurrence of two or more pregnancy losses in the initial 13 weeks gestation, and affects one to two percent of women, or one in every 100 pregnancies. A control group of 271 non-RSA patients were also included for comparative analysis.

The findings revealed a majority of women with RSA possessed the gene mutation of FOXD1. However, in the control group, the gene led researchers to believe it could have a protective effect when in its normal state.

"Our results have also shown that FOXD1 is possibly a new molecular actor modulating pregnancy maintenance, with mutations associated with ER in mice and RSA in humans" wrote the researchers.

This discovery could help doctors give a more effective diagnosis of a potential miscarriage, and devise new treatments for women with this mutation.

FOXD1 isn't the first gene linked to early pregnancy loss. The MTHFR gene is an enzyme that is involved in amino acid metabolism in the body. Common mutations in this gene can affect how a person's body processes homocysteine, an amino acid found in the blood. Women with MTHFR gene mutations are more likely to have elevated levels of homocysteine — a potential risk factor for miscarriages. These mutations can also lead to a decreased ability to metabolize folic acid and other B vitamins.

Similarly, a 2001 study in Austria linked unexplained miscarriage to the specific gene variation known as NOS3. Women who carry this gene tend to produce less nitric oxide. In the uterus, nitric acid causes blood vessels to expand, therefore improving blood flow to the uterus and the growing fetus.

So, is a miscarriage genetic? Maybe.

The discovery of various genetic mutations linked to repeated miscarriages can be discouraging for some women who possess the gene, but staying positive and not giving up has often led to a successful pregnancy. 

Source: Laissue .P, Lakhal B., Vatin M et al. Association of FOXD1 variants with adverse pregnancy outcomes in mice and humans. Royal Society Journal Open Biology. 2016.