Genetics and Epigenetics in Miscarriage

A miscarriage is the loss of a fetus before the 20th week of pregnancy. About 15% of recognized pregnancies will end in a miscarriage, and the occurrence of recurrent miscarriage (RM) has been estimated 1-3% of couples attempting to bear children. Miscarriage could be a very unhappy and frightening and lonely experience.

According to previous study results, fetal chromosomal abnormalities are responsible for 70% of sporadic miscarriages, besides, maternal thrombophilic, anatomic, endocrine, and immunological disorders also increase the risks of miscarriage. Thus, early recognition of risks to miscarriage and systematic monitoring will help increasing live birth rates in miscarriag couples. Genetic and epigenetic factors that are involved in (un)successful pregnancy are currently popular research focus, such as directly address parental- and allele-specific gene expression or epigenetic modifications in placenta. Multiple genetic and epigenetic factors has been found to decrease sperm quality causing DNA damage and thus leading to poor fertilization, impaired embryo development. The balance of locally produced pro-inflammatory and anti-inflammatory cytokines is also indicated to be critical for successful pregnancy.

At present, previous studies have exhibited positive association between identified gene variants and an increased risk to miscarriage, more studies begin to focus on the genes involved in the function of placenta, carrying maternally and paternally originated gene copies.

As discussed in the previous post, maternal and paternal epigenetic regulation governing the control of gene expression has been demonstrated to be an important factor of placental development and function. Epigenomic marks thus exhibit high correlation with miscarriage, including DNA methylation, histone modifications in chromatin, and non-coding regulatory RNAs.

During pregnancy, the main features in placental epigenome include dynamics-changes in epigenetic marks, organization of the DNA methylome, abundance of parental-specific imprinted genes, gene imprinting, placenta-specific microRNAs, effect of environmental factors, e.g., maternal smoking. Epigenome dysfunction may imply the potential miscarriage. For example, Methyltransferase (G9aMT) and methylated histone (H3-K9) expressions are found to be significantly lower in endometrial tissue of miscarriage cases compared to controls. Also, APC and imprinted PEG3 are reported to have more abnormal methylation values in chorionic villus of abortions/stillbirth than other genes. A recent study shows the association between two SNPs in pre-miR-125a and increased risk to miscarriage. The above may be strong perspectives in miscarriage research and potential clinical implications.

Every child is a gift from God. More studies are essential to better cherish these gifts. Furthermore, extensive collaborative network between research centers and miscarriage clinics is needed to be greatly enhanced.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.