Mitochondrial DNA haplogroup H association with endometriosis and possible role in inflammation and pain

Abstract

Introduction: Endometriosis is an inflammatory disease characterised by the presence of endometrial-like tissue outside the uterus and affects approximately 10%–15% of women in their reproductive years. Pain is one of the predominant symptoms of the disease. Oxidative stress is involved in the pathophysiology of endometriosis and develops when there is an imbalance between the reactive oxygen species and reactive nitrogen species production, and the elimination capacity of antioxidants in the reproductive tract. High levels of reactive oxygen species can induce pain indirectly through oxidative stress-associated inflammation or directly through sensitising the nociceptive neurons that transmit the signals to the cerebral sensory cortex which are perceived as a feeling of pain. Mitochondria are the main source of reactive oxygen species, which generate through oxidative phosphorylation. Given that the mitochondria are involved in reactive oxygen species formation and energy production, which are required for the activation and proliferation of peripheral lymphocytes, it has been suggested that mitochondrial DNA variants are involved in the pathogenesis of endometriosis. This study has provided a better understanding of maternally inherited risk factors which contribute to the pain mechanisms associated with endometriosis. Results: Mitochondrial DNA haplogroup H was found to be significantly higher in women with endometriosis. This study was the first to report the association between the European mitochondrial haplogroup H and the risk of pain associated with endometriosis. Discussion: The results suggest that there are maternally inherited risk factors in women with endometriosis causing high reactive oxygen species production and oxidative stress, which facilitate pain generation in women with endometriosis.

Analysis of characteristic genes and ceRNA regulation mechanism of endometriosis based on full transcriptional sequencing

“…After the inflammatory response is activated, it stimulates tissue nerve endings by releasing inflammatory factors, so as to participate in the formation of pain (McKinnon et al, 2015). In recent years, a large number of studies have shown that inflammatory response and emergency response participate in the pathological process of EMS (Samimi et al, 2019;Asally et al, 2020;Wei et al, 2020). A variety of inflammatory factors are differentially expressed in Frontiers in Genetics frontiersin.org EMS patients, which can promote the occurrence of EMS, and also play an important role in the generation of pelvic pain in EMS patients (Ayubi and Safiri, 2017).…”

Polycystic Ovary Syndrome and Oxidative Stress—From Bench to Bedside

“…MtDNA is circular and double-stranded. It comprises a molecule which is 16,569 bp in length and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that are essential for adenosine triphosphate (ATP) production [ 31 , 32 ]. Unlike nuclear DNA, which is located in the cell nucleus and inherited from both parents, mtDNA is inherited in a maternal pattern only [ 33 ].…”

“…Due to its unique inheritance pattern, mtDNA may be used to trace maternal lineages and study human population genetics. It is less prone to recombination and has a higher mutation rate compared to nuclear DNA, making it useful for analyzing evolutionary relationships and population history [ 31 , 34 ]. Any defects at the level of mtDNA replication affect the formation of numerous mutations, whereas mtDNA exhibits a lack of histone protection and a DNA damage repair system [ 35 ].…”