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

Ann Med. 2022 Dec;54(1):2975-2989. doi: 10.1080/07853890.2022.2136401.

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 messagesOur 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.

Keywords: Biomarkers; Differentially expressed genes; Gene therapy; Insulin resistance; Polycystic ovary syndrome.

MeSH terms

  • Biomarkers
  • Contraceptives, Oral
  • Female
  • Humans
  • Insulins*
  • Polycystic Ovary Syndrome* / diagnosis
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / genetics
  • Pregnancy
  • Sirtuin 1

Substances

  • Sirtuin 1
  • Biomarkers
  • Contraceptives, Oral
  • Insulins

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.