Talin1 regulates glucose metabolism and endometrial receptivity via GLUT-4 in patients with polycystic ovary syndrome and insulin resistance

Gynecol Endocrinol. 2023 Dec;39(1):2231085. doi: 10.1080/09513590.2023.2231085.

Abstract

Objectives: Talin1 is a cytoskeletal protein and is localized between cells and the extracellular matrix. This study aimed to investigate the mechanism by which Talin1 affects glucose metabolism and endometrial receptivity via glucose transporter proteins-4 (GLUT-4) in patients with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Methods: We examined the expression of Talin1 and GLUT4 in the receptive endometrium of PCOS-IR and control patients. GLUT4 expression was examined after silencing and overexpression of Talin1 in Ishikawa cells. We validated the interaction between Talin1 and GLUT-4 proteins using a co-immunoprecipitation (Co-IP) assay. After successfully establishing the C57BL/6j mouse model of PCOS-IR, the expression of Talin1 and GLUT-4 were examined in PCOS-IR and control mice. The effect of Talin1 on embryo implantation and the number of live births in mice were examined. Results: Our study found low expression of Talin1 and GLUT-4 in the receptive endometrium of PCOS-IR patients compared to that in control patients (p < 0.01). The level of GLUT-4 expression decreased after silencing Talin1 in Ishikawa cells and increased after overexpression of Talin1. Co-IP results showed that Talin1 interacts with GLUT-4 protein. We successfully established a PCOS-IR C57BL/6j mouse model and found that Talin1 and GLUT-4 expression in the receptive endometrium of PCOS-IR mice were lower than that in control mice (p < 0.05). In vivo experiments confirmed that the knockdown of Talin1 affects embryo implantation (p < 0.05) and live birth rate in mice (p < 0.01). Conclusions: Talin1 and GLUT-4 expression were decreased in the endometrium of PCOS-IR patients, and Talin1 may affect glucose metabolism and endometrial receptivity through GLUT4.

Keywords: Endometrial receptivity; GLUT4; Talin1; insulin resistance; polycystic ovary syndrome.

MeSH terms

  • Animals
  • Endometrium / metabolism
  • Female
  • Glucose / pharmacology
  • Humans
  • Insulin / metabolism
  • Insulin Resistance* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism

Substances

  • Glucose
  • Insulin
  • SLC2A4 protein, human
  • TLN1 protein, human