Screening target genes for the treatment of PCOS via analysis of single-cell sequencing data

Abstract

Background Polycystic ovary syndrome (PCOS) is a condition of the female reproductive system and it remains imperative to identify target genes responsible for its pathogenesis and develop therapeutic drugs capable of effectively treating it. Methods We performed primary screening, staging, functional analysis as well as screening of target genes and therapeutic drugs based on single cell sequencing data of 34 oocytes from the GEO database. Results Oxidative phosphorylation played a pivotal role in the development of oocytes, insulin resistance and ovulation disorders. At the cellular level, GV and MI phases were particularly critical for the biology of pregnancy. We screened PGR , SIRT1 and ADAMTS1 as hub differentially expressed genes (DEGs) and found relevant drugs using the Drug-Gene Interaction Database. In clinical study, oral contraceptives and insulin sensitisers were found to be effective in the treatment of PCOS. Conclusion PGR , SIRT1 and ADAMTS1 were found to be down-regulated in oocytes, ovulation and female pregnancy. These 3 genes are likely biomarkers important in the treatment of PCOS. Insulin sensitiser in combination with oral contraceptive administration were found to significantly improve PCOS. Key messages Our study used a new bioinformatics approach to find target genes for the treatment of PCOS. Our study sought to identify target genes that affect human oocyte quality by analysing single-cell sequencing data from oocytes. We testified to our data by analysing a subset of clinical data.

Effects of n-3 PUFA supplementation on oocyte in vitro maturation in mice with polycystic ovary syndrome

“…Wan et al found that Sirt1 could be an important biomarker in PCOS treatment through single-cell sequencing data analysis of oocytes from PCOS patients [ 28 ]. Downregulation of the Sirt1/Nrf2 pathway, a classical antioxidative stress pathway, has been found to play an important role in oocyte quality decline and spindle morphology abnormalities caused by aging [ 29 ].…”

Follicular development and ovary aging: single-cell studies

“…Moreover, two studies evaluated transcriptome data from oocytes at various developmental stages and determined that the GV and MI phases are especially significant for PCOS patients' reproductive health [136, 137]. Using scRNA-seq data from healthy and PCOS oocytes at various stages of maturation, researchers determined the mitochondrial dynamics of PCOS oocytes and investigated whether aberrant mitochondrial function is connected with developmental failure of oocyte in PCOS patients.…”

“…Excitingly, research has been conducted on the molecular pathology of PCOS. When it comes to the treatment of PCOS, scientists has discovered that the combination of insulin sensitizers and oral contraceptives greatly improved PCOS using the drug–gene interaction database without being certified by single-cell studies [136]. Hence, we ought to employ single-cell technology to explore new therapeutic mechanisms in order to formulate new treatment strategies and better benefit PCOS patients.…”

“…At the level of the transcriptome, however, aging has a higher impact on MII oocytes than on GV oocytes [122]. Another group discovered that PGR, silent information regulator 1 (SIRT1) and a disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) were downregulated in oocytes using single-cell sequencing data from 34 oocytes in the GEO database [136]. Consistently, PGR regulates follicle rupture by inducing ovulation target genes in rats, such as Adamts1, which may unravel the mechanism of ovulation abnormalities in PCOS patients [139].…”