Lysine Acetylation in Granulosa Cells of PCOS Women Regulated by Carbohydrate Metabolism

Abstract

ContextLower‐quality embryos are often found in Polycystic Ovary Syndrome (PCOS) women during assisted reproductive technology treatment; however, there is still a lack of a reliable marker to predict the outcomes of fertilization and embryo development in the clinic.ObjectiveThe aims of this study were to comparatively profile protein lysine acetylation in ovarian granulosa cells, to understand its potential effect on ovarian function at the posttranslational modification level and to establish a reliable marker to predict embryo quality in women with PCOS.DesignThis study recruited 47 PCOS patients and 55 non‐PCOS controls. Mural granulosa cells were collected during oocyte retrieval surgery. A quantitative analysis of acetylated proteomics was carried out by mass spectrometry. The clinical presentations and outcomes of the patients with different acetylation levels in their granulosa cells were analyzed.ResultsIn the granulosa cells, there was widespread lysine acetylation of proteins, of which 265 proteins had increased levels of acetylation and 68 proteins had decreased levels of acetylation in the PCOS group. Most notably, differentially acetylated proteins were significantly enriched in the metabolic pathways of glycolysis/gluconeogenesis, fatty acid degradation and amino acid biosynthesis. In addition, women with PCOS with enhanced acetylation in their granulosa cells had markedly reduced 2 pronuclear (2PN) rates, numbers of available embryos and rates of available embryos.ConclusionThe dynamic levels of lysine acetylation in the granulosa cells of women with PCOS might alter ovarian metabolic homeostasis and can be a marker to reflect embryo quality in the clinic.Support or Funding InformationThis work was supported in part by the National Key R&D Program of China (2016YFC1000601) and the National Natural Science Funds (81571400, 81771580, and 81971381).