Dorien O

Proteomic Biomarkers for Endometriosis

Endometriosis is a benign, estrogen-dependent gynecology disorder associated with pelvic pain and infertility. It is characterized by the presence of endometrial-like tissue outside the uterine cavity, mainly on the pelvic peritoneum and ovaries and in the rectovaginal septum and more rarely in the pericardium, the pleura, and even the brain. The etiology and pathogenesis remains unclear. The most accepted theory is Sampson’s theory: retrograde menstruation. The gold standard of diagnosing endometriosis is through laparoscopy.

Optimization of Endometrial Decidualization in the Menstruating Mouse Model for Preclinical Endometriosis Research

Background: To induce endometrial decidualization in rodents, an intrauterine oil stimulus can be delivered via the nontraumatic vagina or via the traumatic laparotomy. However, there is considerable variation in amount of decidualization using these inducing methods. Therefore, we studied which oil delivery route could achieve the highest rate of endometrial decidualization along the full length of both uterine horns. Methods: To induce decidualization, ovariectomized C57Bl/6J mice were injected with estrogen (100 ng/day; 3 days). A progesterone pellet (5 mg) was implanted subcutaneously, followed by estrogen injections (5 ng/day; 3 days). Oil (20 µL/horn) was injected in the uterus via laparotomy, laparoscopy, or vagina. Four days later, the pellet was removed, followed by hysterectomy after 4 to 6 hours. Endometrial decidualization was evaluated macroscopically and microscopically using hematoxylin and eosin and desmin staining. Furthermore, uterine weight and hormone levels were measured. Results: The proportion of animals with macroscopic bicornuate decidualization was higher after laparoscopic (83%) and laparotomic (89%) injection than after sham injection (11%). Furthermore, macroscopic bicornuate decidualization was significantly higher after laparotomic injection (89%) compared to the vaginal injection (38%). Uterine weight and endometrial surface area were significantly higher in both laparotomy and laparoscopy groups compared to the sham group, while the relative desmin-positive endometrial surface area was only significantly different between the laparotomy and the sham animals. Conclusion: Methods using laparoscopic and laparotomic intrauterine oil injection resulted in a higher amount of decidualized endometrium compared to sham injection, although further optimization is needed to reach full bicornuate decidualization.

Functional Expression of TRP Ion Channels in Endometrial Stromal Cells of Endometriosis Patients

Endometriosis is a common gynecological disease that is characterized by the presence of functional endometrial-like lesions in the abdominal cavity. Aside from epithelial cells, these lesions consist of stromal cells that have the capacity to migrate, adhere, proliferate, and induce neuro- and lymphangiogenesis, which allows them to survive at ectopic locations. However, the exact underlying mechanisms that regulate these changes are yet to be elucidated. The common ground of these processes, however, is the second messenger, calcium. In this regard, members of the superfamily of transient receptor potential (TRP) ion channels, which are known to be calcium-permeable and expressed in the endometrium, have emerged as key regulators. Here, we assessed the molecular and functional expression of TRP channels in stromal cells isolated from the eutopic endometrium of endometriosis patients and controls. Using RT-qPCR, high mRNA levels of TRPV2, TRPV4, TRPM4, TRPM7, TRPC1, TRPC3, TRPC4, and TRPC6 were observed in the whole endometrium throughout the menstrual cycle. Additionally, and in line with previous reports of control patients, TRPV2, TRPV4, TRPC1/4, and TRPC6 were present in human endometrial stromal cells (hESC) from endometriosis patients both at the molecular and functional level. Moreover, proliferation and migration assays illustrated that these parameters were not affected in stromal cells from endometriosis patients. Furthermore, comparison between eutopic and ectopic endometrial samples revealed that the RNA expression pattern of TRP channels did not differ significantly. Collectively, although a functional expression of specific ion channels in hESCs was found, their expression did not correlate with endometriosis.

Peripheral Blood Biomarkers for Endometriosis

Endometriosis is a complex disease to study and diagnose. Ultrasound can be used to diagnose cysts and endometrioma but cannot rule out peritoneal endometriosis. Endometriosis is defined as endometrium outside of uterus. It is associated with infertility and pain. If we find a diagnostic test to diagnose endometriosis in blood it would be a convenient, most probably cheap test that would discriminate women who are suffering from endometriosis from those who do not. Till today, we do not have a diagnostic test for endometriosis. For women it is a heavy psychological burden, and quick diagnosis would help reduce this burden. Studies have shown that endometriosis cost arises predominantly from productivity loss and is predicted by decreased quality of life. In this chapter we describe and discuss the current status of biomarkers (miRNAs, glycoproteins, immunological, angiogenic, cell adhesion/invasion factors) of endometriosis in peripheral blood.