Divergent expression of two prostaglandin E receptors (EP1 and EP3) in normal endometrium and in ovarian endometriosis

Jianjun Zhu, Viktoria von Schönfeldt, Udo Jeschke
In: Geburtshilfe und Frauenheilkunde · 2016 · vol. 76(04) · doi:10.1055/s-0036-1580648 · W2344236997
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This study investigated and compared the expression levels of prostaglandin receptors EP1 and EP3 in normal endometrium and ovarian endometriosis.

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This study compared prostaglandin E receptor expression in normal endometrium versus ovarian endometriosis, analyzing immunohistochemistry from 46 women across menstrual-cycle phases and ectopic endometrial tissue from 15 endometriosis patients. EP1 expression was significantly higher in glandular cells and stromal cells during the proliferative phase than the early secretory phase, and EP1 was also higher in ectopic endometrial tissues; by contrast, EP3 expression showed opposite changes, being downregulated in glandular cells during the proliferative phase relative to early secretory phase and in ectopic tissues, with no EP3 differences in stromal cells. A key limitation is that the work focused on semiquantitative receptor expression differences rather than direct functional outcomes on implantation or endometriosis mechanisms. This paper is centrally about endometriosis — it specifically demonstrates divergent EP1 and EP3 expression patterns in normal endometrium versus ovarian endometriosis.

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Abstract

Both the implantation and endometriosis are the results of complicated interaction of sex hormones, prostaglandins and cytokines that designate tissue to adhesion, migration and apoptosis. EP1 and EP3 have been implicated to promote these actions, respectively. Although the crucial role of prostaglandins play in diverse physiological and pathological processes is known, the possible effects of their receptors on implantation remain to be elucidated. Here we investigate the expression levels of prostaglandin receptivity in normal endometriums in comparison to that of ovarian endometriosis.
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Background

Both the implantation and endometriosis are the results of complicated interaction of sex hormones, prostaglandins and cytokines that designate tissue to adhesion, migration and apoptosis. EP1 and EP3 have been implicated to promote these actions, respectively. Although the crucial role of prostaglandins play in diverse physiological and pathological processes is known, the possible effects of their receptors on implantation remain to be elucidated. Here we investigate the expression levels of prostaglandin receptivity in normal endometriums in comparison to that of ovarian endometriosis.

Material and methods

Normal endometrial tissues of 46 patients from at all phases of the menstrual cycle (n = 16 from proliferative, n = 15 from early secretory and n = 15 from late secretory) as well as ectopic endometrial tissues from 15 endometriosis patients were included and routinely processed for immunohistochemistry. The expression of EP1 and EP3 was quantified by immunohistochemical staining using a semiquantitative immunoreactive score (IRS).

Results

EP1 expression of both glandular cells (P < 0.001) and stromal cells (p < 0.05) was significantly higher during the proliferative phase of the menstrual cycle than during the early secretory phase. EP3 expression of glandular cells was also significantly higher in ectopic endometrial tissues (P < 0.001). In contrast, analysis of EP3 expression revealed the exact opposite pattern: EP3 expression was significantly downregulated in glandular cells during the proliferative phase compared with the early secretory phase of the menstrual cycle (P < 0.05) and in ectopic endometrial tissues (P < 0.05). Stromal cells showed no differences in EP3 expression.

Discussion

Here, we demonstrate the divergent expression of EP1 and EP3 in endometrial tissues: While EP1 expression decreases during the window of implantation in normal endometrial tissues and increases in ectopic endometrial tissues, EP3 expression behaves in the opposite way. The mutually oppositional changes of EP1 and EP3 expression hint at a tightly orchestrated expression to facilitate implantation and might play an important role in the pathophysiology of endometriosis.

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endometriosis

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