Embryos generated from oocytes lacking complex N- and O-glycans have compromised development and implantation

Area of Science:

• Reproductive Biology
• Developmental Biology
• Glycobiology

Background:

• Complex N- and O-glycans are crucial for various biological processes.
• Oocyte quality and function are essential for successful reproduction.
• Premature ovarian failure (POF) significantly impacts female fertility.

Purpose of the Study:

• To investigate the impact of lacking complex N- and O-glycans in oocytes on female reproductive function.
• To determine the basis for reduced litter size and premature ovarian failure in double mutant mice.
• To evaluate ovulation rate, embryo development, and implantation in mice with defective oocyte glycosylation.

Main Methods:

• Generation of double mutant (DM) mice lacking complex N- and O-glycans in oocytes (Mgat1(F/F)C1galt1(F/F):ZP3Cre).
• Evaluation of ovulation rates at different time points (6 and 9 weeks).
• In vitro and in vivo assessment of zygote development to blastocyst stage.
• Analysis of pre- and post-implantation embryo development and implantation rates.

Main Results:

• DM females exhibited normal ovulation at 6 weeks, declining by 9 weeks, and showed premature ovarian failure by 3 months.
• In vitro embryo development was normal, but embryos lacked a proper zona pellucida (ZP).
• In vivo, DM females had reduced embryo recovery, delayed development (morula vs. blastocyst), impaired implantation, and consequently, smaller litters.

Conclusions:

• A lack of complex N- and O-glycans in oocytes severely impairs early embryo development and viability in vivo.
• Defective oocyte glycosylation leads to delayed implantation and contributes to reduced litter size and premature ovarian failure.
• These findings highlight the critical role of oocyte glycan structures in successful reproduction.