Syncytin-a deficiency compromises murine sperm function by suppressing PRL/PGE2 and PI3K/AKT/mTOR pathway

Area of Science:

• Reproductive biology
• Endocrinology
• Genetics

Background:

• Human endogenous retrovirus W envelope protein syncytin-1 (syncytin-a in mice) is implicated in development and cancer.
• Its role in male infertility remains uncharacterized.

Purpose of the Study:

• To investigate the function of syncytin-a in male reproductive health.
• To elucidate the molecular mechanisms underlying syncytin-a deficiency-induced male infertility.

Main Methods:

• Construction of a prostatic epithelial-specific syncytin-a knockout (syna CKO) mouse model.
• Analysis of male reproductive parameters, sperm characteristics, and gene expression.
• Investigation of signaling pathways (PI3K/AKT/mTOR, Ca2+) and apoptosis markers.

Main Results:

• Syna CKO mice exhibited male infertility, abnormal testicular and prostate structures.
• Sperm motility, morphology, and MMAF-associated gene expression (AKAP3, SPAG6) were irregular.
• Increased prostaglandin E2 (PGE2) and prolactin (PRL) affected testicular lipid metabolism.
• Syncytin-a knockout inhibited the PI3K/AKT/mTOR pathway and Ca2+ levels, while elevating caspase 3 expression.

Conclusions:

• Syncytin-a deficiency exacerbates testicular lipid accumulation and apoptosis.
• Suppression of PI3K/AKT/mTOR and Ca2+ pathways contributes to spermatogenic dysfunction.
• Syncytin-a plays a crucial role in maintaining male fertility.