Loss of FUT8 impairs embryonic development by reducing cAMP production in granulosa cells

In cases of impaired fertility, the quality of oocytes and their subsequent embryonic development following fertilization are critical concerns in clinical practice. Core fucosylation, catalyzed by fucosyltransferase 8 (FUT8), is a common N-glycosylation modification that plays a key role in cell proliferation and signal transduction. This study examines the role of core fucosylation in follicular regulation during oocyte development.

Patients were categorized into two groups based on their embryo formation rates. Core fucosylation levels, catalyzed by FUT8, were assessed in serum and follicular fluid (containing granulosa cells). To investigate the molecular effects of FUT8 on oocyte quality, FUT8-knockdown human granulosa cells (KGN-KD), and ovaries from Fut8 gene knockout (Fut8^-/-) mice were analyzed.

Core fucosylation levels were lower in patients with reduced blastocyst formation rates. FUT8 depletion led to decreased cAMP production following follicle-stimulating hormone (FSH) stimulation in both KGN-KD and the ovaries of Fut8^-/- mice. Additionally, the expression of FIGLA (folliculogenesis-specific basic helix-loop-helix transcription factor) and other genes associated with embryonic development was downregulated in the ovaries of Fut8^-/- mice. Oocytes from Fut8^-/- mice exhibited abnormal zona pellucida formation and impaired embryonic development.

These findings indicate that FUT8 ablation may disrupt embryonic development post-fertilization by reducing FSH receptor (FSHR) signaling and downregulating FIGLA expression. The results suggest that core fucosylation is essential for female reproduction and oocyte quality.