Expression Pattern of G-Protein-Coupled Estrogen Receptor in Myometrium of Uteri with and without Adenomyosis.

OBJECTIVE: To compare the expression of G-protein-coupled estrogen receptor (GPER) in the junctional zone and outer myometrium of the proliferative and secretory phases of women with and without adenomyosis. METHODS: A total of 76 women were included in this study, 42 with adenomyosis (proliferative phase, n = 23; secretory phases, n = 19) and 34 controls (proliferative phase, n = 16; secretory phases, n = 18). Protein and total RNA were extracted from the junctional zone (JZ) and outer myometrium (OM). GPER protein and mRNA expression levels were evaluated by the use of western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression of GPER protein and mRNA in women with adenomyosis was significantly higher than that of control subjects, both in the junctional zone and in the outer myometrium and both in the proliferative and in the secretory phases. CONCLUSION: The significant and consistent increase in GPER expression in adenomyosis compared with control subjects, regardless of whether it was in the proliferative or secretory phases and regardless of whether it was in the JZ or OM, suggests that GPER plays an important role in the pathogenesis of the adenomyosis.

Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

BACKGROUND AIMS: Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models. METHODS: Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured. RESULTS: Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri. CONCLUSIONS: hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria.

Efficacy of freeze-dried amnion graft following hysteroscopic adhesiolysis of severe intrauterine adhesions.

OBJECTIVE: To evaluate the efficacy of freeze-dried amnion graft for prevention of intrauterine adhesion (IUA) reformation after hysteroscopic adhesiolysis. METHODS: A prospective randomized controlled trial was conducted among 88 women with severe IUAs who underwent hysteroscopic adhesiolysis at Beijing Obstetrics and Gynecology Hospital between July 15, 2015, and July 1, 2016. All participants had a balloon inserted into the uterine cavity for 1 week. Sterilized freeze-dried amnion graft covered the balloon portion of the Foley catheter among patients allocated to the amnion group (n=44), whereas patients in the control group (n=44) did not receive the graft. Follow-up hysteroscopy was performed 3 months after surgery. Preoperative and postoperative IUA scores, menstruation scores, and pregnancy rates were assessed. RESULTS: Both groups exhibited reductions in IUA scores and improvements in menstruation scores following treatment (P<0.001 for each measure). Compared with the control group, the amnion group had a lower IUA score (P=0.032) and a higher menstruation score (P<0.001) at follow-up. By contrast, the rates of IUA reformation and pregnancy were not significantly different between the two groups. CONCLUSION: Use of freeze-dried amnion graft was effective in reducing IUA reformation and improving menstruation (according to pictorial blood-loss assessment chart) following hysteroscopic adhesiolysis of severe IUAs. ClinicalTrials.gov: (NCT02496052).

17ß-Estradiol Induces Overproliferation in Adenomyotic Human Uterine Smooth Muscle Cells of the Junctional Zone Through Hyperactivation of the Estrogen Receptor-Enhanced RhoA/ROCK Signaling Pathway.

Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. Recent models favor abnormal thickening of the junctional zone (JZ) may be the causative factor in the development of ADS. RhoA, a small guanosine triphosphatase which controls multiple cellular processes, is involved in the control of cell proliferation. Here we demonstrate that treatment of human uterine smooth muscle cells (SMCs) of the JZ with 17ß-estradiol (E2) increased expression of RhoA and its downstream effectors (-associated coiled coil containing protein kinase [ROCK] 1 and ROCK2). Compared with non-ADS cells, RhoA, ROCK1, and ROCK2 were overexpressed and hyperactivated in ADS cells. These effects were suppressed in the presence of ICI 182,780, supporting an estrogen receptor (ER)-dependent mechanism. Hyperactivation of ER-enhanced RhoA/ROCK signaling was associated with overproliferation in ADS human uterine SMCs of the JZ. Moreover, E2-induced overproliferation was accompanied by downregulation of cyclin-dependent kinases inhibitors (CKIs; p21(Waf1/Cip1) and p27(Kip1)) and upregulation of cyclin-dependent kinases (CDKs) and cyclins (cyclin D1, cyclin E1, CDK2, CDK4, and CDK6).

Radical trachelectomy versus radical hysterectomy for the treatment of early cervical cancer: a systematic review.

OBJECTIVE: To assess the efficacy and safety of radical trachelectomy (RT) and radical hysterectomy (RH) for patients with early cervical cancer. DESIGN: Systematic review with meta-analysis. POPULATION: Women who had early cervical cancer. METHODS: Prospective controlled clinical trials comparing RT with RH were identified using a predefined search strategy. Recurrence, five-year recurrence-free survival rate, five-year overall survival rate, postoperative mortality, intraoperative and postoperative complications between the two operations were compared by using the methods provided by the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Three controlled clinical trials involving 587 participants were included. Meta-analysis showed that there was no significant difference between the two groups in recurrence rate [1.38; 95% confidence interval (CI) 0.58-3.28, p=0.47], five-year recurrence-free survival rate (1.17; 95% CI 0.54-2.53, p=0.69), five-year overall survival rate (0.86; 95% CI 0.30-2.43, p=0.78), postoperative mortality (1.14; 95% CI 0.42-3.11, p=0.80), intraoperative complications (1.66; 95% CI 0.11-25.28, p=0.72), postoperative complications (0.52; 95% CI 0.11-2.48, p=0.41), blood transfusion (0.29; 95% CI 0.06-1.36, p=0.12) and number of harvested lymph nodes. However, RT, compared with RH, reduced blood loss and shortened duration to normal urine residual volume and postoperative hospital stay. Moreover, RT may achieve to normal conception rates, while RH makes patients sterile. CONCLUSIONS: Radical trachelectomy has similar efficacy and safety to RH as the surgical treatment for early cervical cancer. Moreover, it reduced blood loss and shortened the duration to normal urine residual volumes and postoperative hospital stay. Radical trachelectomy can be used to treat early stage cervical cancer as an alternative operation for patients who wish to preserve fertility.