Glucocorticoids impair oocyte competence and trigger apoptosis of ovarian cells via activating the TNF-α system

Area of Science:

• Reproductive Biology
• Endocrinology
• Cellular Biology

Background:

• Glucocorticoids, stress hormones, are known to affect reproductive function.
• The precise mechanisms by which glucocorticoids impair oocyte competence and induce apoptosis remain incompletely understood.
• Previous research suggests glucocorticoids may trigger apoptosis via the FasL/Fas system or other pathways.

Purpose of the Study:

• To investigate the hypothesis that glucocorticoids induce apoptosis in oocytes and ovarian cells by activating the tumor necrosis factor-alpha (TNF-α) system.
• To elucidate the role of the TNF-α system in mediating the adverse effects of glucocorticoids on female reproductive cells.

Main Methods:

• In vivo experiments involving cortisol injection in female mice.
• In vitro studies using corticosterone treatment on ovarian cells.
• Assessment of oocyte developmental potential, mitochondrial membrane potential, and oxidative stress.
• Analysis of TNF-α system activation and expression.
• Gene knockdown or knockout of TNF-α to evaluate its role.

Main Results:

• Cortisol impaired oocyte developmental potential and mitochondrial membrane potential, increasing oxidative stress.
• Cortisol induced apoptosis and oxidative stress in mural granulosa cells (MGCs).
• Glucocorticoids activated the TNF-α system in ovaries and oocytes, but downregulated it in oviductal epithelial cells.
• TNF-α knockdown/knockout significantly reduced glucocorticoid-induced apoptosis in oocytes and MGCs.

Conclusions:

• Glucocorticoids impair oocyte competence and trigger apoptosis in ovarian cells primarily through the activation of the TNF-α system.
• The TNF-α pathway is a key mediator of glucocorticoid-induced reproductive toxicity.
• The impact of glucocorticoids on TNF-α expression is cell-type specific.