TREK-1 confers differential effects on contractile dynamics in myometrium and the oviduct, indicating a unique role in endometriosis and labor
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Authors
Ramirez, Mairani Vanessa
Issue Date
2025
Type
Thesis
Language
en_US
Keywords
Endometriosis , Fallopian tube , Preterm Labor , Reproductive health , TREK-1 , Uterus
Alternative Title
Abstract
Roughly 6-13% of reproductive age females (114-247 million) globally are affected by endometriosis, a life-altering condition with no cure causing extreme pain during periods, infertility, and even depression and anxiety. Ten percent of women undergo labor prematurely in the United States, which is a leading cause of neonatal morbidity and mortality. Both endometriosis and preterm labor are considered to be inflammation- related conditions potentially caused by hormonal and/ or immune dysregulation with a higher prevalence of interleukin 6 (IL-6), a pro-inflammatory cytokine produced by circulating immune cells including B and T-cells. IL-6 has been found to increase oxytocin receptors in the myometrium, leading to an increase in contractility. It has been established that TREK-1, a potassium channel, plays a major role in quiescing the myometrium, which is essential for maintaining pregnancy. However, the effects of IL-6 and the role of TREK-1 in the fallopian tube have yet to be fully determined. We hypothesize that an increase in IL-6 leads to reduced contractile activity in the fallopian tube and increased contractility in the myometrium, which may contribute to endometriosis and preterm labor. IL-6 leads to a decrease in TREK-1 expression in the myometrium, leading to a decrease in the ability to remain in a relaxed state. TREK-1 expression is increased in the fallopian tube as a result of IL-6 presence, leading to its dilation, allowing for retrograde movement of menses material. Though not statistically significant, the organ bath results show a trend that mouse uterine horns incubated in the presence of IL-6 result in increased contractility compared to control. In both IL-6 and control uterine tissues, contractility showed a downward trend when dosed with the TREK-1 agonist ML335. It was determined that oviducts incubated in IL-6 had a decreased contractile response after washout compared to oviducts which were not exposed to IL-6, and both groups had a similar level of contractility relative to control when exposed to ML335. TREK-1 protein expression was found to be significantly increased in oviduct samples treated with IL-6. Based on these findings we have concluded TREK-1 portrays differential effects on contractile dynamics in the myometrium and the oviduct, indicating a unique role in endometriosis and labor which will be further investigated in the future.