Fertilization offsets the maternal age effect on mouse oocytes provided the oviduct is not itself aged
- 1Max Planck Institute for Molecular Biomedicine
Abstract
Advanced maternal age compromises oocyte quality, and it is widely assumed that these deficits are transmitted to embryos. However, because most studies rely on in vivo conception, it has been difficult to separate the effects of oocyte aging from those of an aged fertilization environment. In aging mice, we observed that the fraction of ovulated oocytes forming implantation sites after in vivo conception fell ~3.7-fold, raising the question of whether this was due to reduced fertilization, reduced embryo quality or reduced support from the aged reproductive tract. Therefore we fertilized oocytes of aged and young mice in vitro with a shared young-donor sperm preparation, holding the fertilization environment constant and removing paternal variability. Hallmarks of maternal age were largely offset following fertilization in vitro: aged oocytes produced blastocysts at rates comparable to young controls, with altered - but not deficient - cell-lineage composition and no detectable impairment in development to term (E18.5) after transfer to young oviducts. Proteomic analysis revealed that, unlike the transcriptomic signature, the proteomic age signature of oocytes was not faithfully propagated to the blastocyst: for a subset of proteins, particularly those depleted in aged oocytes, the direction of the age effect reversed between oocyte and blastocyst. Comparison with parthenogenetically activated oocytes showed this divergence to be fertilization-dependent, implicating fertilization - rather than mere embryonic cleavage - as the driver of proteomic change. Stable-isotope labelling in live embryos showed that blastocysts from aged, fertilized oocytes both synthesized more new protein and retained less maternal protein than young counterparts; neither effect was detectable after parthenogenesis. Puromycin labelling, by contrast, showed a maternal-age-associated rise in bulk synthesis regardless of route. Together, these results indicate that the maternal-age effect on the oocyte proteome is labile rather than fixed and can be offset by fertilization itself, provided the maternal environment is not itself aged.
Related
- Spatiotemporal expression and hormonal regulation of antioxidant enzymes in the bovine oviduct epithelium
- Climate Change Finance and Carbon Offsets: Addressing Global Climate Challenges through Innovative Funding and Emissions Reduction Mechanisms
- Active mechanics of sea star oocytes
- Cnidarian oocytes reveal conserved actin-driven mechanisms of female meiosis
- Myristic acid promotes in vitro maturation and developmental competence of porcine oocytes
BibTeX
@misc{boiani2026fertilization,
title = {{Fertilization offsets the maternal age effect on mouse oocytes provided the oviduct is not itself aged}},
author = {M. Boiani and T. Nolte and J. Wiese and G. Fuellen and A. Buechsenschuetz and S. Winter and H. C. A. Drexler},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.761756},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.761756v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fertilization offsets the maternal age effect on mouse oocytes provided the oviduct is not itself aged
AU - M. Boiani
AU - T. Nolte
AU - J. Wiese
AU - G. Fuellen
AU - A. Buechsenschuetz
AU - S. Winter
AU - H. C. A. Drexler
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.761756
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.761756v1
AB - Advanced maternal age compromises oocyte quality, and it is widely assumed that these deficits are transmitted to embryos. However, because most studies rely on in vivo conception, it has been difficult to separate the effects of oocyte aging from those of an aged fertilization environment. In aging mice, we observed that the fraction of ovulated oocytes forming implantation sites after in vivo conception fell ~3.7-fold, raising the question of whether this was due to reduced fertilization, reduced embryo quality or reduced support from the aged reproductive tract. Therefore we fertilized oocytes of aged and young mice in vitro with a shared young-donor sperm preparation, holding the fertilization environment constant and removing paternal variability. Hallmarks of maternal age were largely offset following fertilization in vitro: aged oocytes produced blastocysts at rates comparable to young controls, with altered - but not deficient - cell-lineage composition and no detectable impairment in development to term (E18.5) after transfer to young oviducts. Proteomic analysis revealed that, unlike the transcriptomic signature, the proteomic age signature of oocytes was not faithfully propagated to the blastocyst: for a subset of proteins, particularly those depleted in aged oocytes, the direction of the age effect reversed between oocyte and blastocyst. Comparison with parthenogenetically activated oocytes showed this divergence to be fertilization-dependent, implicating fertilization - rather than mere embryonic cleavage - as the driver of proteomic change. Stable-isotope labelling in live embryos showed that blastocysts from aged, fertilized oocytes both synthesized more new protein and retained less maternal protein than young counterparts; neither effect was detectable after parthenogenesis. Puromycin labelling, by contrast, showed a maternal-age-associated rise in bulk synthesis regardless of route. Together, these results indicate that the maternal-age effect on the oocyte proteome is labile rather than fixed and can be offset by fertilization itself, provided the maternal environment is not itself aged.
ER -