Connexin expression pattern in the endometrium of baboons is influenced by hormonal changes and the presence of endometriotic lesions

Abstract

Experimentally induced endometriosis in baboons serves as an elegant model to discriminate between endometrial genes which are primarily associated with normal endometrial function and those that are changed by the presence of endometriotic lesions. Since connexin genes are characteristic of the hormonally regulated differentiation of the endometrium, we have examined connexin expression in baboon endometrium to delineate if they are altered in response to the presence of endometriotic lesions. Connexin expression in the endometrium of cycling baboons is similar to that of the human endometrium with Connexin(Cx)43 being primarily seen in the stromal compartment and Cx26 and Cx32 being present predominantly in the epithelium. Although Cx32 is up-regulated during the secretory phase, Cx26 and Cx43 are down-regulated. In the baboon model of induced endometriosis a change in connexin pattern was evident in the presence of endometriotic lesions. In the secretory phase, Cx26 and Cx32 are no longer present in the epithelium but Cx26 is now observed primarily in the stromal cells. Infusion of chorionic gonadotrophin in a manner that mimics blastocyst transit in utero failed to rescue the aberrant stromal expression of Cx26 that is associated with the presence of endometriotic lesions suggesting an impairment of the implantation process. The altered connexin pattern coupled with a loss of the channel protein in the epithelium and a gain of Cx26 in the stromal compartment suggests that the presence of lesions changes the uterine environment and thereby the differentiation programme. This aberrant expression of connexins may be an additional factor that contributes to endometriosis-associated infertility.

Figure 1

(A–C) Immunohistochemistry of baboon endometrium in the proliferative phase.

Figure 2

(A–C) Immunohistochemistry of baboon endometrium in the secretory phase.

Figure 3

(A–C) Immunohistochemistry of baboon endometrium after CG infusion. Cx43 is expressed in the stromal compartment but not in the epithelium showing the plaque reaction (A). There is neither an immunoreaction to Cx26 (B) nor to Cx32 (C). (D–E) Immunohistochemistry of baboon endometrium after CG infusion and induced endometriosis (10–15 month). There is no obvious change of Cx43 immunostaining in the stromal compartment (D). Cx26 is expressed in the stromal compartment (E), Cx32 is not detected (F). E, epithelium; S, stroma. Bar = 100 µm.

Figure 4

Quantitative Real-Time RT–PCR analysis of transcripts of Cx26 (A), Cx43 (B) and Cx32 (C) in endometrium of the proliferative phase (PP), and secretory phase (SP) of healthy animals, and secretory phase of induced endometriosis (SP EMT).