Background: Female reproductive health is noticeably compromised by obesity. The underlying mechanisms remain to be elucidated. Accumulating evidence indicates that the expression level of ovarian Kiss1 peaks in the afternoon during prooestrus, suggesting local regulatory roles for Kiss1 in the ovulatory process. We used a diet-induced model of obesity to evaluate whether the ovarian Kiss1 system is affected by obesity, and, to investigate the association of the Kiss1 system with ovulatory disorders in female rats. Methods: Post-weaning, female, Sprague-Dawley rats were randomly fed either a high-fat diet (HFD) or a normal chow diet (NCD) until they reached postnatal day 30 (PND 30), PND 42, or PND 70. The timing of vaginal opening was recorded, and oestrous cyclicity was monitored for 2 consecutive weeks immediately post puberty and again at 8-9 weeks of age. Tissues from the left ovary were collected for determination of the levels of Kiss1 and G protein-coupled receptor 54 (GPR54) mRNA, and tissues from the right ovary were collected for assessment of the immunoreactivity (IR) of the corresponding protein products, kisspeptin and GPR54. Results: The high-fat diet resulted in a significantly higher body weight and an earlier puberty onset. Oestrous cyclicity was disrupted by the HFD with significant reductions in the expression of ovulation-related genes. A marked suppression of ovarian Kiss1 mRNA levels was observed during prooestrus and oestrus at PND 42, and, during prooestrus, oestrus, and metoestrus at PND 70 in the HFD rats compared with the NCD controls. In the HFD group, the immunoreactivity of kisspeptin was significantly lower in theca cells from antral follicles during prooestrus and oestrus at PND 42, and, during prooestrus, oestrus at PND 70. At the prooestrus stage, in the HFD group the immunoreactivity of kisspeptin was also lower in the theca cells of preovulatory follicles at both PND 42 and PND 70.
Emerging studies showed that lncRNA taurine upregulated 1 (TUG1) plays important roles in diverse biological processes. However, there is no previously published research reporting the regulatory role of lncRNAs in the progression of adenomyosis. In the present study, we found that TUG1 is upregulated in human adenomyosis, and the overexpression of TUG1 is associated with the transcription factor early growth response 1 (EGR1). Functionally, the knockdown of TUG1 inhibited adenomyotic epithelial cell migration and invasion but not growth. The mechanistic experiments demonstrated that the function of TUG1 in adenomyotic epithelial cell invasion is, at least in part, through recruiting the enhancer of zeste homolog 2 (EZH2) to the promoter of tissue inhibitor of metalloproteinases 2 (TIMP2) and negatively regulating its expression. Our study demonstrated that TUG1 promotes the migration and invasion of human adenomyotic epithelial cells, and EGR1/TUG1/EZH2/TIMP2 may be a potential therapeutic target for adenomyosis.
Abstract. To investigate the clinicopathological features, management and prognosis of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix, the current study presents 4 cases of VGPA of the uterine cervix. The median age of the patients was 55 years (range, 47-70 years), with all 4 patients presenting with stage Ib disease. Human papillomavirus (HPV) infection was detected in 3 patients; this was mainly HPV-16. No history of oral contraceptive use was found in these cases. While 2 of the patients underwent a radical hysterectomy with bilateral salpingo-oophorectomy plus bilateral pelvic lymphadenectomy, 1 patient underwent a radical hysterectomy with bilateral pelvic lymphadenectomy and the remaining patient received a simple total hysterectomy plus post-operative radiotherapy. Of these patients, only 1 had been correctly diagnosed pre-operatively. In 2 patients, the biopsy results had been interpreted as cervical adenocarcinoma, and in the third, the biopsy result was of cervical intraepithelial neoplasia. All 4 patients presented with cervical wall invasion, including invasion of the inner two-thirds in 1 patient. No lymphovascular space invasion or lymph node metastasis was detected. The follow-up time ranged from 49 to 83 months (median, 64 months), and the patients are currently alive and well, with no evidence of recurrent disease. Taking these results as a whole, VGPA is an uncommon type of cervical adenocarcinoma, characterized by its excellent prognosis. HPV infection is associated with the molecular pathogenesis of VGPA, while oral contraceptive use can be excluded. As the disease has a low pre-operative diagnostic accuracy, frequent cervical wall invasion and concomitant lesions, conservative treatment strategies should be carefully considered.
Objective To develop and validate a nomogram for predicting pelvic lymph node metastasis (LNM) in cervical squamous cell carcinoma (SCC). Methods This was a retrospective study that included 715 patients with cervical SCC who underwent radical hysterectomy and bilateral pelvic lymphadenectomy between 2009 and 2018. Logistic regression analysis was used to identify independent risk factors for pelvic LNM. Based on these risk factors, a nomogram predicting LNM risk was constructed and internally validated using the bootstrapping resampling method. Results The rate of LNM in FIGO (the International Federation of Gynecology & Obstetrics) Stage IA2–IIA2 cervical SCC was 24.2%. In multivariate analysis, FIGO Stage II, moderately differentiated or poorly differentiated histology, abnormally elevated serum SCC‐antigen, and triglyceride were identified as independent risk factors for LNM. Tumor size greater than 2 cm and parametrial involvement had borderline significance. Ultimately, the nomogram contained the six variables mentioned above, showing positive calibration and positive discrimination. The area under the receiver operating characteristic curvewas 0.827 and the bootstrap‐validated C‐index was 0.827. The Youden index of this paper was 0.540. Conclusions We developed and validated a nomogram to predict pelvic LNM in SCC based on clinical data, which can help physicians develop an optimal treatment strategy.
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