Hu Min, Li Juan, Zhang Yuehui, Li Xin, Brännström Mats, Shao Linus R, Billig Håkan
Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg Gothenburg 40530, Sweden.
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University Guangzhou 510120, China.
Am J Transl Res. 2018 Aug 15;10(8):2696-2705. eCollection 2018.
Polycystic ovary syndrome (PCOS) affects approximately 4%-18% of all reproductive-aged women and is often accompanied by endometrial progesterone (P4) resistance. Endometrial cells from PCOS patients display increased progesterone receptor (PGR) expression; however, in vivo knockout studies and in vitro experiments indicate the two PGR isoforms are not functionally equivalent.
We aimed to compare endometrial PGR isoform expression between non-PCOS and PCOS patients during the proliferative phase.
A case-control study. The expression of PGR isoforms (PGRA and PGRB), estrogen receptor alpha (ERα), and markers of cell proliferation was determined by qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence assays.
PATIENT(S): Patients were recruited and diagnosed with PCOS according to the Rotterdam criteria provided by the American Society for Reproductive Medicine and the European Society for Human Reproduction and Embryology. Endometrial biopsy samples were collected from non-PCOS patients with regular menstrual cycles or with hyperplasia (n = 11) and from PCOS patients with or without hyperplasia (n = 14).
RESULT(S): Although the alteration of PGRB mRNA and protein expression was different, we found that PGRA mRNA and protein expression was higher in PCOS patients than non-PCOS patients. PGRA/B and PGRB were localized in both epithelial and stromal cells, with notable changes in the nuclei of epithelial and stromal cells. A similar expression pattern of ERα, vimentin and Ki-67, in association with an increased PGR expression, was observed in PCOS patients.
CONCLUSION(S): These results demonstrated that elevated both PGR isoform expression depends on the presence of PCOS, and our data suggest that abnormal regulation of PGR isoforms is a pathological outcome of defective endometrium in PCOS patients.
多囊卵巢综合征(PCOS)影响着约4%-18%的育龄妇女,且常伴有子宫内膜孕酮(P4)抵抗。PCOS患者的子宫内膜细胞显示孕酮受体(PGR)表达增加;然而,体内基因敲除研究和体外实验表明两种PGR亚型在功能上并不等同。
我们旨在比较增殖期非PCOS和PCOS患者之间子宫内膜PGR亚型的表达情况。
一项病例对照研究。通过qRT-PCR、蛋白质免疫印迹、免疫组织化学和免疫荧光测定法来确定PGR亚型(PGRA和PGRB)、雌激素受体α(ERα)的表达以及细胞增殖标志物。
根据美国生殖医学学会和欧洲人类生殖与胚胎学会提供的鹿特丹标准招募并诊断为PCOS的患者。从月经周期正常或有增生的非PCOS患者(n = 11)以及有或无增生的PCOS患者(n = 14)中采集子宫内膜活检样本。
尽管PGRB mRNA和蛋白质表达的变化不同,但我们发现PCOS患者中PGRA mRNA和蛋白质表达高于非PCOS患者。PGRA/B和PGRB定位于上皮细胞和基质细胞中,上皮细胞和基质细胞核中有明显变化。在PCOS患者中观察到与PGR表达增加相关的ERα、波形蛋白和Ki-67的类似表达模式。
这些结果表明两种PGR亚型表达升高均取决于PCOS的存在,并且我们的数据表明PGR亚型的异常调节是PCOS患者子宫内膜缺陷的病理结果。