Obesity

The Impact of High Adiposity on Endometrial Progesterone Response and Metallothionein Regulation

J Clin Endocrinol MetabPublished Mechanistic study

Authors' conclusion

Taken together, the in vitro and in vivo systems used here revealed that high adiposity or obesity can alter MT expression by decreasing progesterone response in the epithelial cells and increasing oxidative stress in the stroma.

Study context

Population
Benign endometrial tissues from premenopausal women ages 33 to 53 undergoing hysterectomy, with and without obesity, Northwestern University Prentice Women's Hospital, Chicago
Comparison
High adiposity vs normal conditions; women with vs without obesity
Outcome
Effects of high adiposity on endometrium
Methodological detailsin vitro coculture system, native human endometrial tissue analysis
  • In vitro coculture system
  • Native human endometrial tissue analysis

Main finding

As reported in the abstract

  • Under high adiposity, endometrial organoids downregulated secretory phase genes, suggesting altered progesterone response
  • Progesterone specifically upregulated the metallothionein (MT) gene family in organoid epithelial cells; high adiposity significantly downregulated MT genes
  • Silencing MT genes in endometrial epithelial cells increased DNA damage
  • Native endometrium from women with obesity showed increased MT expression and oxidative damage in the stroma, not the epithelium

Original publication

The Impact of High Adiposity on Endometrial Progesterone Response and Metallothionein Regulation. J Clin Endocrinol Metab. Published 10 April 2024. doi:10.1210/clinem/dgae236

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