JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

The Role of Endoplasmic Reticulum Stress in Polycystic Ovary Syndrome and Exploration of Potential Therapeutic Targets

  • 0The Department of Obstetrics and Gynecology, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi, 716000, China.
Reproductive Sciences (thousand Oaks, Calif.) +

|

August 14, 2025

|

August 14, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Endoplasmic reticulum (ER) stress is implicated in polycystic ovary syndrome (PCOS). This study identifies key ER stress genes for a diagnostic model and potential drug targets for PCOS.

Area Of Science

  • Endocrinology
  • Genetics
  • Immunology
  • Pharmacology

Background

  • Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women.
  • Endoplasmic reticulum (ER) stress is increasingly recognized for its role in PCOS pathogenesis.

Purpose Of The Study

  • To explore the role of ER stress in PCOS by developing a predictive model using ER stress-related genes.
  • To evaluate immune infiltration characteristics and screen potential therapeutic drugs for PCOS.

Main Methods

  • Utilized Lasso, SVM, RF, XGB, and GLM algorithms to identify key ER stress-related genes in PCOS.
  • Constructed and validated a predictive nomogram model for PCOS diagnosis.
  • Performed immune infiltration analysis and molecular docking for drug screening.

Main Results

  • Identified five key genes (NQO1, NPY, TFEB, JUP, ATF4) associated with ER stress in PCOS.
  • The predictive model demonstrated good reliability for PCOS diagnosis (AUCs ranging from 0.543 to 0.743).
  • Found correlations between gene expression (JUP, TFEB, NPY) and T lymphocyte infiltration, suggesting immune regulation involvement.
  • Screened 66 potential drugs, including 18 already approved, for modulating the ER stress pathway in PCOS.

Conclusions

  • ER stress-related genes are significantly involved in the pathogenesis and development of PCOS.
  • The developed predictive model offers potential for early PCOS diagnosis.
  • Immune infiltration analysis provides insights into immune cell involvement in PCOS.
  • Drug screening results offer a theoretical basis for targeted PCOS therapies.

Keywords:

Related Concept Videos

Role of ER in the Secretory Pathway 01:17

5.6K

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...

Smooth Endoplasmic Reticulum 01:21

6.2K

Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...

Regulation of the Unfolded Protein Response 01:31

2.6K

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

Oogenesis 02:07

64.4K

In human women, oogenesis produces one mature egg cell or ovum for every precursor cell that enters meiosis. This process differs in two unique ways from the equivalent procedure of spermatogenesis in males. First, meiotic divisions during oogenesis are asymmetric, meaning that a large oocyte (containing most of the cytoplasm) and minor polar body are produced as a result of meiosis I, and again following meiosis II. Since only oocytes will go on to form embryos if fertilized, this unequal...

The Unfolded Protein Response 01:37

5.1K

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

Hormonal Control of the Ovarian Cycle 01:30

2.8K

The ovarian cycle is meticulously regulated by the hypothalamic-pituitary-gonadal axis. This cycle orchestrates the release of a mature oocyte, essential for reproduction.
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle.  At puberty, GnRH secretion increases in both frequency and...