RESUMO
OBJECTIVES: Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism. METHODS: A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR. RESULTS: The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05). CONCLUSIONS: Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.
Assuntos
Síndrome do Ovário Policístico , Criança , Gravidez , Humanos , Feminino , Apoptose , Células da Granulosa , Metabolismo dos Lipídeos , Proteínas de Membrana , Receptores de ProgesteronaRESUMO
OBJECTIVE: To evaluate long term effect and related factors in patients with menorrhagia treated by microwave endometrial ablation (MEA). METHODS: Total of 334 women with menorrhagia were treated by MEA, the range of age was from 29 to 59 years old. Among them, 59 cases were complicated by adenomyosis. All the patients were followed up on the change of menstrual cycle, the amount of flow, improvement of anaemia and complication. Fifty-three women underwent outpatient diagnostic hysteroscopy, the biopsy tissue was taken from the endometrium for histopathological examination. The mean duration of follow-up was 64.7 months (3 - 96 months). RESULTS: The overall curative rate was 91.3% (305/334), of which amenorrhea rate was 49.7% (166/334), menstruation reduction rate was 41.6% (139/334) ; 71.1% (140/197) of the cases who previously had dysmenorrhea had relieved their pelvic pain and the satisfactory rate was 91.9% (307/334). Among patients > 40 years, 92.9% (196/211) of operation effective rate, 93.8% (198/211) of satisfactory rate and 64.9% (137/211) of amenorrhea rate were obtained, while patients = 40 years, 88.6% (109/123) of operation effective rate, 88.6% (109/123) of satisfactory rate and 23.6% (29/123) of amenorrhea rate were obtained. There was significant difference in rate of operation effectiveness, satisfaction and amenorrhea (P < 0.05). Forty-two cases required subsequent treatment due to recurrence, of which 9 cases were given by secondary MEA and 33 cases (9.9%, 33/334) underwent hysterectomy indicated by frequent menorrhagia, adenomyosis or leiomyoma. A completely destroyed endometrium was observed by hysteroscopy after MEA, pathologic characteristics of MEA showed two zones of necrotic tissue: the inner zone was coagulation necrosis and the outer zone of necrosis was hypocellular hyalinized myometrium. CONCLUSIONS: MEA is the safe and efficacious management to treat menorrhagia. Incomplete removal of endometrium was the major reason resulting in postoperative recurrence. Young age and complicated with adenomyosis were the main factors influencing long term clinical effect of MEA.