Li Da, You Yue, Bi Fang-Fang, Zhang Tie-Ning, Jiao Jiao, Wang Tian-Ren, Zhou Yi-Ming, Shen Zi-Qi, Wang Xiu-Xia, Yang Qing

Center of Reproductive MedicineShengjing Hospital of China Medical University, Shenyang, China.| Department of Obstetrics and GynecologyShengjing Hospital of China Medical University, Shenyang, China.| Department of Obstetrics and GynecologyShengjing Hospital of China Medical University, Shenyang, China.| Department of PediatricsShengjing Hospital of China Medical University, Shenyang, China.| Center of Reproductive MedicineShengjing Hospital of China Medical University, Shenyang, China.| Center of Reproductive MedicineShengjing Hospital of China Medical University, Shenyang, China.| Department of ObstetricsGynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.| Department of MedicineBrigham and Women's Hospital, Harvard Institutes of Medicine, Harvard Medical School, Boston, Massachusetts, USA.| Center of Reproductive MedicineShengjing Hospital of China Medical University, Shenyang, China.| Center of Reproductive MedicineShengjing Hospital of China Medical University, Shenyang, China yangq@sj-hospital.org wangxxsj@sina.cn.| Department of Obstetrics and GynecologyShengjing Hospital of China Medical University, Shenyang, China yangq@sj-hospital.org wangxxsj@sina.cn.

Reproduction. 2018 Jan;155(1):85-92. doi: 10.1530/REP-17-0499. Epub 2017 Oct 13.

The importance of autophagy in polycystic ovary syndrome (PCOS)-related metabolic disorders is increasingly being recognized, but few studies have investigated the role of autophagy in PCOS. Here, transmission electron microscopy demonstrated that autophagy was enhanced in the ovarian tissue from both humans and rats with PCOS. Consistent with this, ovarian granulosa cells from PCOS rats showed increases in the autophagy marker protein light chain 3B (LC3B), whereas levels of the autophagy substrate SQSTM1/p62 were decreased. In addition, the ratio of LC3-II/LC3-I was markedly elevated in human PCOS ovarian tissue compared with normal ovarian tissue. Real-time PCR arrays indicated that 7 and 34 autophagy-related genes were down- and up-regulated in human PCOS , Signal-Net, and regression analysis suggested that there are a wide range of interactions among these 41 genes, and a potential network based on EGFR, ERBB2, FOXO1, MAPK1, NFKB1, IGF1,TP53 and MAPK9 may be responsible for autophagy activation in PCOS. Systematic functional analysis of 41 differential autophagy-related genes indicated that these genes are highly involved in specific cellular processes such as response to stress and stimulus, and are linked to four significant pathways, including the insulin, ERBB, mTOR signaling pathways and protein processing in the endoplasmic reticulum. This study provides evidence for a potential role of autophagy disorders in PCOS in which autophagy may be an important molecular event in the pathogenesis of PCOS.

Shi Lin, Liu Shan, Zhao Wanqiu, Shi Juanzi

Department of Immunology and Microbiology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.| Assisted Reproduction Center, Maternal and Child Health Care Hospital of Shaanxi Province, Xi'an 710003, China.| Assisted Reproduction Center, Maternal and Child Health Care Hospital of Shaanxi Province, Xi'an 710003, China.| Assisted Reproduction Center, Maternal and Child Health Care Hospital of Shaanxi Province, Xi'an 710003, China. Electronic address: shijuanzi123@126.com.

Reprod Biomed Online. 2015 Oct;31(4):565-72. doi: 10.1016/j.rbmo.2015.06.023.

The aim of this study was to compare the expression of microRNAs (miRNAs) in cumulus cells from polycystic ovary syndrome (PCOS) and non-PCOS women. In the present study, miRNA expression profiles of the cumulus cell samples were determined by miRNA microarrays. Quantification of selected miRNAs and predicted target genes was performed using quantitative real-time PCR (qRT-PCR). The results showed that miR-483-5p and miR-486-5p are significantly decreased in cumulus cells of PCOS patients PCOS (fold change >2, false discovery rate <0.001). qRT-PCR found that four predicted genes, SOCS3, SRF, PTEN and FOXO1, were significantly increased in PCOS cumulus cells (all P < 0.001), and IGF2 (host gene of miR-483-5p) was significantly decreased in PCOS cumulus cells (P < 0.001). These results indicated that miR-483-5p might play an important role in reducing insulin resistance, and that miR-486-5p might promote cumulus cell proliferation through activation of PI3K/Akt. The findings from this study provided new insights into the complex molecular mechanisms involved in PCOS by revealing pathways possibly regulated by miRNAs. The differences in miRNAs (miR-483-5p, miR-486-5p) and their target gene expression in cumulus cells may provide clues for future research and help to explain aberrant follicular development and subfertility in women with PCOS.

Li Ning, Wang Xiaoyan, Wang Xiaojie, Yu Hongna, Lin Li, Sun Chengming, Liu Peng, Chu Yongli, Hou Jianqing

Clin Lab. 2017 Feb 1;63(2):301-311. doi: 10.7754/Clin.Lab.2016.160514.

BACKGROUND: Chronic activation of macrophage-mediated inflammatory signals in insulin-sensitive metabolic tissues is thought to be one of the causes of insulin resistance-one of the hallmarks of the metabolic syndrome. Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial and endothelial function.
METHODS: In the present study, we investigated the phosphorylation level of FoxO 1, which is suppressed by the action of AKT, triggers the TLR4 inflammatory signaling pathway in the macrophages, from polycystic ovary syndrome patients or normal subjects. Then we investigated the influence of phosphorylation level of FoxO 1FoxO 1 on the induction of proinflammatory cytokines in the macrophages and the influence by FoxO FoxO 1 knockdown on the insulin-induced glucose uptake in PCOS macrophages.
RESULTS: Our results demonstrated that the significantly high level of FoxO 1FoxO 1 phosphorylation correlated with the production of proinflammatory cytokines, such as IL-6, IL-1beta, and TNF-alpha in the macrophages from PCOS patients. The high level of FoxO 1FoxO 1 phosphorylation enhanced the TLR-4 signaling in response to LPS, and the FoxO FoxO 1 knockdown inhibited the insulin-induced glucose uptake in PCOS macrophages.
CONCLUSIONS: The findings of this paper suggest an intriguing regulatory transcriptional/signaling loop in macrophages that may contribute to maintain and exacerbate inflammation and insulin resistance in PCOS macrophages.