Analysis of Clusterin and Clusterin Receptors in the Endometrium and Clusterin Levels in Cervical Mucus of Endometriosis

Clusterin (CLU) is expressed in tissues and body fluids and is altered in some pathologies. In endometriosis, a noninvasive test is still lacking, thus, we analyzed CLU in mucus samples of patients. Additionally, we investigated localization of CLU and the putative CLU receptors (apolipoprotein E receptor 2 [ApoER2], megalin, very low-density lipoprotein receptor [VLDLR], and transforming growth factor β receptor type I and II [TβR1/TβR2]). In mucus samples, CLU levels are modestly, but not significantly, higher in cases with endometriosis compared to cases without endometriosis, however, CLU levels are significantly (P = .02) reduced in patients with endometriosis receiving contraception compared to cases with endometriosis without contraception. Analysis of CLU and CLU receptors showed CLU mainly in the uterine epithelial cells in the majority of glands, but also in endothelial cells. Similarly, ApoER2 and TβR1 could also be found preferentially in the endometrial glands. Whereas ApoER2 staining was strong in the vessels, TβR1 was modestly expressed in vessels and muscle cells. In contrast, staining of VLDLR and TβR2 was modest in the glands but stronger in vessels and muscle cells. Megalin staining was faint in the glands. A similar pattern for these proteins could be observed in adenomyosis. We demonstrate for the first time high concentrations of CLU in mucus samples and significantly reduced CLU levels in cases with endometriosis receiving contraception compared to cases with endometriosis without contraception. Furthermore, we identified uterine epithelial and endothelial cells as the main source of CLU and found different preferential CLU receptor complexes on glands, vessels, and smooth muscle cells.