Abstract
Interleukin 6 (IL-6) is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL) for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001) as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.
Highlights
Interleukin-6 (IL-6) is a pleotropic cytokine which is known to activate acute phase proteins and maintain chronic inflammatory states ranging from cardiovascular diseases to infertility [1]
Effect of IL-6 on microtubules To determine the effects of IL-6 on metaphase-II mouse oocytes, oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL) for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls
It is well established that maintenance of the integrity of the mature oocyte spindle is vital for proper cell division and embryo formation [24]
Summary
Interleukin-6 (IL-6) is a pleotropic cytokine which is known to activate acute phase proteins and maintain chronic inflammatory states ranging from cardiovascular diseases to infertility [1]. IL-6 has been known to be involved in the pathogenesis of small vessel diseases, accelerate joint inflammation and destruction in rheumatoid arthritis, and contribute to neurovascular disease such as dementia [2,3,4] This preinflammatory cytokine is known to be expressed and reactive oxygen species (ROS) are known to be elevated in patients with chronic pain syndromes, acute pelvic inflammatory disease, idiopathic infertility and patients with endometriosis [5,6,7,8,9]. We explored the direct effect of various concentrations of IL-6 on the metaphase-II mouse oocyte spindle and chromosomal alignment in vitro, as a possible mechanism of deterioration of oocyte quality in patients with pelvic inflammatory states where IL-6 levels are elevated
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