The abnormal expression of oxytocin receptors in the uterine junctional zone in women with endometriosis

Abstract

Background: The junctional zone (JZ), also called as the endometrial-myometrial junction, is related to peristaltic-like movements in the non-pregnant uterus. Hyperperistalsis and dysperistalsis of uterus constructions might underlie many important disorders such as dysmenorrhea, infertility, endometriosis, implantation failure. The major proteins for uterine contraction of the non-pregnant uterus may be Oxytocin (OT) and oxytocin receptor (OTR). The objective of this study was to inspect the expression of OTR in isthmic and mid-fundal parts of the uterine junctional zone at different stages of the follicular cycle in patients with and without endometriosis.

Methods: Uterine biopsies containing endometrium and junctional zone were collected from the isthmic and mid-fundal parts of the anterior wall after hysterectomy. The OTR expression was evaluated by immunohistochemistry.

Results: In the control uterus, OTR expression in the isthmic region was significantly higher than in the fundal region in the proliferative phase (p < 0.05) but significantly lower in the secretory phase (p < 0.05). And the expression of OTR in the proliferative phase was significantly higher than that in the secretory phase in both isthmic and fundal regions (p = 0.000 and 0.049, respectively). However, in endometriosis uteri, OTR expression in the isthmic region showed no significant difference with that in the fundal region in both proliferative and secretory phases (p = 0.597 and 0.736, respectively). In both isthmic and fundal regions, OTR expression was not significantly different between the proliferative phase and secretory phase (p = 0.084 and 0.222, respectively). OTR expression in fundal regions of revised ASRM I and II endometriosis were lower than that of revised ASRM III and IV (p = 0.049). In the fundal region of JZ, the expression of OTR in ovarian endometriosis was significantly lower than that in deep infiltrating endometriosis (p = 0.046). The expression level of OTR in the funds region is positively associated with the severity of dysmenorrhea in endometriosis group (r = 0.870, p < 0.05). Comparing to normal uteri, the expression of OTR in the secretory phase was significantly higher in the endometriosis uteri (p < 0.05). In the fundus of endometriosis uteri, OTR expression was significantly higher in both the proliferative and secretory phases (p = 0.045 and 0.028, respectively).

Conclusion: OTR expression in the JZ of women with endometriosis changes significantly, which may result in abnormal uterine contractile activity, reducing the endometriosis-related fertility and dysmenorrhea.

Keywords: Endometriosis; Junctional zone; Oxytocin receptor.

Fig. 1

Representative staining of mild cytoplasmic OTR expression in myometrial cells of JZ in the control group (arrow). a Isthmus region in the proliferative phase. b Fundus in the proliferative phase. c Isthmus region in the secretory phase. d Fundus region in the secretory phase

Fig. 2

Comparisons of oxytocin expression level in the isthmus and fundus of control uterus in different menstrual cycles. OTR expression in the isthmic region was significantly higher than in the fundal region in the proliferative phase (p < 0.05) but significantly lower in the secretory phase (p < 0.05). In both isthmic and fundal regions, OTR expression in the proliferative phase was significantly higher than that in the secretory phase (p < 0.05). OTR expression in patients with dysmenorrhea of control group was no significant difference from that of patients without in both isthmic and fundal regions of JZ (p > 0.05). Data are expressed as mean ± standard error of the mean

Fig. 3

Representative staining of strong cytoplasmic OTR expression in myometrial cells of JZ in the endometriosis group (arrow). a Isthmus region in the proliferative phase. b Fundus in the proliferative phase. c Isthmus region in the secretory phase. d Fundus region in the secretory phase

Fig. 4

Comparisons of oxytocin expression level in the isthmus and fundus of endometriosis uterus in different menstrual cycles. OTR expression was not significantly between the isthmic and fundal regions in both proliferative and secretory phases. (p > 0.05). In both isthmic and fundal regions, the expression of OTR in the proliferative phase was not significantly different from secretory phase (p > 0.05). In the fundal region of JZ, the expression of OTR in ovarian endometriosis was significantly lower than that in deep infiltrating endometriosis (p < 0.05). Data are expressed as mean ± standard error of the mean

Fig. 5

Comparisons of oxytocin receptor expression level between control and endometriosis uteri in the proliferative and secretory phases. In the isthmic region, the expression of OTR in the secretory phase was significantly higher in the endometriosis uteri (p < 0.05). In the fundal region of endometriosis uteri, the expression of OTR was significantly higher than that in the control uteri in both the proliferative and the secretory phases (p < 0.05). Data are expresses as mean ± standard error of the mean

Fig. 6

The severity of dysmenorrhea measured by the VAS as function of the OTR expression levels in women with endometriosis. OTR expression level in the funds region is positively correlated with the severity of dysmenorrhea (r = 0.872, p < 0.05)