Aberrant expression of angiopoietin-like proteins 1 and 2 in cumulus cells is potentially associated with impaired oocyte developmental competence in polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with obesity, insulin resistance, hyperandrogenism, alterations in ovarian angiogenesis and impaired oocyte competence. Emerging evidence demonstrates that angiopoietin-like protein 1 (ANGPTL1) and angiopoietin-like protein 2 (ANGPTL2) have an important influence on angiogenesis, androgen biosynthesis, insulin resistance and adipocytes function. In this study, we set out to determine the potential relationship between ANGPTL1, ANGPTL2 and oocyte competence in PCOS through analyzing the expression levels and dynamic pattern of the two genes in cumulus cells (CCs) during different phases of nuclear maturation of PCOS patients and control groups undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer. We found that the relative abundance of ANGPTL1 and ANGPTL2 transcripts in CCs from patients with PCOS showed dynamic changes during oocyte maturation. Specifically, their expressions were increased significantly at the Metaphase II stage. In summary, the present novel evidence indicates that the expression patterns of ANGPTL1 and ANGPTL2 mRNAs are disordered during oocyte maturation in PCOS, which were potentially related to aberrant oocyte quality and developmental potency, at least in part, via pathological angiogenesis and metabolism.

Chinese abstract

多囊卵巢综合征是一种异质性内分泌紊乱性疾病，与肥胖、胰岛素抵抗、雄激素过多、卵巢血管形成改变及卵母细胞功能受损相关。越来越多的证据表明：血管生成素样蛋白-1和2（ANGPTL1和ANGPTL2）对血管生成、雄激素生物合成、胰岛素抵抗及脂肪细胞功能方面有重要影响。在该研究中，我们通过分析PCOS患者与对照组在体外受精—胚胎移植的超控排卵不同阶段卵丘细胞两种基因表达的水平及动态模式，来确定ANGPTL1和ANGPTL2与卵母细胞功能的内在联系。我们发现卵丘细胞中ANGPTL1和ANGPTL2的相对丰度在卵母细胞成熟过程中呈现动态变化。具体说来，他们的表达在细胞分裂中期增长显著。总之，最新数据表明，PCOS患者的ANGPTL1和ANGPTL2 mRNAs的表达类型是紊乱的，至少部分在病理性血管形成及代谢方面影响着卵母细胞的功能。

• ANGPTL1
• ANGPTL2
• oocyte competence
• polycystic ovary syndrome

Acknowledgements

The authors would like to gratefully thank Ning Li, Xiaofang Shen for advice on qPCR technology from the Central Laboratory of Yuhuangding Hospital of Yantai.

Declaration of interest

The authors report no declarations of interest.