SET improved oocyte maturation by serine/threonine protein phosphatase 2A and inhibited oocyte apoptosis in mouse...

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Cellular Processes

Background:

• SET is a multifunctional protein implicated in cell apoptosis and cell-cycle regulation.
• SET is expressed in ovarian theca cells and oocytes, with elevated levels observed in polycystic ovary syndrome (PCOS) patients.
• Understanding SET's role is crucial for elucidating PCOS-related follicular development defects.

Purpose of the Study:

• To investigate the role of SET in mouse oocyte maturation and apoptosis.
• To explore the potential molecular mechanisms underlying SET's function in oocyte development.
• To identify SET as a potential therapeutic target for impaired oocyte developmental competence in PCOS.

Main Methods:

• Oocytes at the germinal vesicle (GV) stage were collected from 6-week-old female ICR mice.
• SET expression was manipulated using AdCMV-SET (overexpression) and AdH1-SiRNA/SET (knockdown) adenoviruses.
• Protein phosphatase 2A (PP2A) activity was assessed, and its inhibition was achieved using okadaic acid (OA).
• Expression levels of BMP15, GDF9, caspase 3, and caspase 8 were analyzed.

Main Results:

• SET overexpression promoted oocyte maturation, while SET knockdown inhibited it.
• SET negatively regulated PP2A activity; PP2A inhibition or knockdown promoted oocyte maturation.
• SET increased the expression of BMP15 and GDF9, whereas PP2A inhibited these factors.
• SET reduced oocyte apoptosis by decreasing caspase 3 and caspase 8 expression.

Conclusions:

• SET promotes oocyte maturation by inhibiting PP2A activity.
• SET inhibits oocyte apoptosis, independent of PP2A.
• SET's regulation of PP2A, BMP15, GDF9, and caspases provides a molecular pathway for its effects on oocyte competence.
• These findings suggest a potential pathological mechanism for impaired oocyte development in PCOS.