Is there an epigenetic link to repeated miscarriages?

304

For any human being, the most heartbreaking experience is going through repeated or recurrent miscarriages. As a couple, people have dreams of having children, and nurturing them into well-mannered and successful adults is all they hope for. However, when they go through something that is as traumatizing as recurrent pregnancies, it affects their mental and physical health greatly. Other than that, individuals who have a history of repeated miscarriages find it hard to have a normal social life as well. 

According to research, twenty-five percent of pregnancies end up in miscarriages. That means, unfortunately, the number of recurrent pregnancy loss cases are pretty common. Most miscarriages take place in the first trimester. 

How can you define recurrent miscarriages? 

Repeated or recurrent miscarriage is defined as having two or more pregnancy losses back to back. 50% of the time, the cause(s) of the miscarriages are not discovered. However, it is crucial to understand that many individuals who undergo such an ordeal will eventually end up having a healthy baby. If you feel that you might be going through something similar, get a professional evaluation by a specialist, who can help you figure out the potential causes of recurrent pregnancy loss. 

What are the main causes of recurrent miscarriages? 

There are many reasons why individuals go through repeated miscarriages. Those include: 

  • Advanced maternal age. 
  • Hormonal imbalance and abnormalities. 
  • Medical conditions such as PCOS (polycystic ovarian syndrome), diabetes, thyroid syndromes, and obesity. 
  • Uterine cavity distortion, which can result from other medical conditions like fibroids, obesity, uterine septum, and polyps. 
  • Asherman’s syndrome in which the uterus has adhesions. 
  • Lupus. 
  • Celiac disease. 
  • Thrombophilia – a condition in which the individual suffers from a high tendency towards the formation of blood clots.
  • Male factor anomalies. 
  • Genetic or chromosomal variants are possible in one or both partners.  (Family Equality)

The role of epigenetic alterations in pregnancy loss 

Pathological epigenetic alterations are significantly crucial in feto-maternal medicine. Diseases that are related to maternal pregnancy such as gestational diabetes and pregnancy-induced hypertension are linked with global or gene-specific modifications of DNA methylation in the placenta. Similarly, diseases in offspring that occur early or later in life are also connected with placental alterations in DNA methylation. While there are many reasons why one should take epigenetic alterations seriously, here are the two grounds that play an important role in placental complications that result in miscarriages. 

  1. The placenta is a sensitive organ that plays an important role as an interphase between mother and child. It controls and monitors fetal exposure to any external environmental factors. For example, the supply of micro and macronutrients, oxygen, and other environmental toxins has a massive impact on early fetal development. 
  2. Just like any other endocrine organ, the placenta secretes important hormones for the fetus and the mother.  Since the hormone secretions influence the phenotype of the mother and the fetus, they can contribute to maternal and offspring diseases. In simple words, the entire development of the placenta, the supply of nutrition from the mother to the baby, and the fetus growth all depend on the epigenetic mechanism. Therefore, even a slight discrepancy in the epigenetic control of placental mechanisms can be the cause of debilitating consequences, such as early miscarriage, abnormality in offspring, and maternal diseases. 

Everything you need to know about Recurrent Pregnancy Loss (RPL) and epigenetic alterations 

One of the most difficult and frustrating areas in feto-maternal medicine is recurrent pregnancy loss (RPL). The known risk factors or mechanisms that are connected to recurrent pregnancy loss, and those that further influence the effect of epigenetic alterations are: 

  • Advancing maternal age. 
  • Increasing parity. 
  • Genetic factors such as abnormalities of chromosome number cause early sporadic pregnancy loss. 
  • Uterine anomalies such as the septate uterus, intrauterine adhesions, synechiae, and leiomyoma. 
  • Endocrine factors such as poorly controlled diabetes mellitus, polycystic ovary syndrome, thyroid antibodies,  hypo- or hyperthyroidism, and hyperprolactinemia. 

All these aforementioned factors contribute to early pregnancy loss. However, in the majority of the cases, the underlying cause is largely unknown. However, when it comes to other feto-maternal diseases, specialists can find evidence that epigenetic mechanisms might be the reason behind the pathogenesis of recurrent pregnancy loss. Other researches have also shown that hypomethylation of CREB5, which is a novel risk gene, can cause dysfunction of trophoblast cells, which can be a major cause of recurrent pregnancy loss. Such results were obtained by performing genome-wide DNA methylation analysis and RNA-seq analysis in decidua tissue. (Hocher, 2018, 18-19)

The role of maternal stress in recurrent pregnancy loss (RPL) 

According to the result of many types of research, fetus development is greatly affected by the mother’s stress, anxiety, and depression. During pregnancy, panic attacks and anxiousness can alter the progressive growth of the baby. Other than that, there is an increased risk for later psychopathology as well. To deal with repeated miscarriages, it is important to understand some underlying mechanisms including gene-environment interaction, placental activities, epigenetics, and other specific systems such as the hypothalamic-pituitary-adrenal axis and cytokines. 

There are a number of reasons that can elevate prenatal stress in mothers such as communities at war. Moreover, individuals can also suffer from raised pregnancy-specific anxiety with high levels of maternal and infant death. In third-world countries, cases like “wife-beating” also contribute to recurrent pregnancy loss. Therefore, raised interpersonal violence should be avoided among partners. Furthermore, nutritional deficiencies can also play a role in prenatal stress and child neurodevelopment.  

Furthermore, people belonging to ethnic groups are also more vulnerable or more resilient to the effects of maternal anxiety. Prenatal depression is also a common cause that can influence the abnormal growth of the fetus and eventual loss of a pregnancy as well. In the modern age,  the scientific world is making more and more advances in the fields of maternal care to mitigate the high-chances of miscarriages. With proper care and professional counseling, you can save your pregnancy from such unfortunate consequences. Most healthcare professionals advise the mother to be as calm as possible that further helps in the reduction of epigenetic alteration during pregnancy. (Glover, 2018)

Get in touch with MBP Inc for filter tips

References 

Family Equality. (n.d.). Recurrent Pregnancy Loss. Family Equality. https://www.familyequality.org/resources/recurrent-pregnancy-loss/?gclid=CjwKCAiAsaOBBhA4EiwAo0_AnDZiX88FsetXAhRLUhnwPD8XU5pzMIl7txAlSfbjAkk4vj33x6YMPhoCixwQAvD_BwE

Glover, V. (2018, August 2). Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology—A global perspective. EBioMedicine. https://www.cambridge.org/core/journals/development-and-psychopathology/article/abs/prenatal-maternal-stress-fetal-programming-and-mechanisms-underlying-later-psychopathologya-global-perspective/0CC0CCF67D96C8174699E4C4D375F29A

Hocher, B. (2018, August 30). Epigenetics of recurrent pregnancy loss. EBioMedicine, 35, 18-19. https://www.thelancet.com/article/S2352-3964(18)30339-6/fulltext#back-bb0015