Genetic and Epigenetic Factors in Recurrent Pregnancy Loss

Recurrent pregnancy loss (RPL), defined as the failure of two or more consecutive clinical pregnancies, affects up to 5% of couples and carries profound psychological and medical consequences. Genetic factors encompass chromosomal anomalies—such as parental balanced translocations and aneuploidies in the conceptus—as well as monogenic variants and polygenic risk profiles that influence coagulation, angiogenesis and trophoblast invasion. Common inherited thrombophilias, including factor V Leiden and prothrombin gene mutations, contribute to an adverse uteroplacental environment. Beyond DNA sequence alterations, epigenetic modifications at the maternal–fetal interface regulate gene expression crucial for implantation and placental development. Aberrant DNA methylation, altered histone marks and dysregulated small non-coding RNAs have been linked to impaired decidualisation, oxidative stress and immune imbalance in RPL. Together, genetic predispositions and epigenetic dysregulation converge on key pathways governing trophoblast function, vascular remodelling and maternal immune tolerance, highlighting targets for personalised risk assessment and potential therapeutic intervention.

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Genetic and Epigenetic Factors in Recurrent Pregnancy Loss publication trend

The graph below shows the total number of articles in genetic and epigenetic factors in recurrent pregnancy loss across all publications each year (not limited to Nature Index journals).

Technical terms

DNA methylation: The addition of methyl groups to cytosine bases in DNA, modulating gene expression without altering the sequence.

Histone modification: Post-translational chemical changes (for example, acetylation or methylation) of histone proteins that influence chromatin structure and transcription.

Chromosomal translocation: A structural rearrangement in which segments from two different chromosomes exchange places, potentially disrupting gene function.

microRNA: Short non-coding RNA molecules that bind complementary mRNA transcripts to inhibit their translation or promote degradation.

References

1. Proteomics profiling reveals lipid metabolism abnormalities during oogenesis in unexplained recurrent pregnancy loss. Frontiers in Immunology (2024).
2. Decreased Expression of Placental Proteins in Recurrent Pregnancy Loss: Functional Relevance and Diagnostic Value. International Journal of Molecular Sciences (2024).
3. Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration. Frontiers in Immunology (2022).
4. Thrombophilia and pregnancy. Reproductive Biology and Endocrinology (2003).
5. Association of Inherited Thrombophilia with Recurrent Pregnancy Loss in Palestinian Women. Obstetrics and Gynecology International (2011).
6. TLR signaling pathway and the effects of main immune cells and epigenetics factors on the diagnosis and treatment of infertility and sterility. Heliyon (2024).
7. Associations of recurrent miscarriages with chromosomal abnormalities, thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia. BMC Medical Genomics (2016).