Timing and duration of alpha-minimum essential medium exposure during preimplantation development determine long-term metabolic phenotypes in mice.

Authors

Yoshiya Morishita, Atsushi Takahashi, Nodoka Umihira, Shiori Ishiyama, Kazuki Mochizuki, Satoshi Kishigami

Published in

The Journal of reproduction and development. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

The environment experienced during preimplantation development can influence long-term health. Continuous culture of mouse preimplantation embryos in α-minimum essential medium (αMEM) for 48 h induces the established "MEM mouse" phenotype, but the critical exposure window and required duration remain unclear. Here, 2-cell embryos were cultured for 48 h in mCZB alone (mCZB), in αMEM for the first 24 h followed by mCZB (M/C), in mCZB for the first 24 h followed by αMEM (C/M), or in αMEM for the full 48 h (MEM). Blastocyst development, lineage allocation, fetal and placental growth, postnatal growth, survival under high-fat diet (HFD), and glucose tolerance were evaluated. Continuous 48 h exposure reduced blastocyst formation, and late or sustained αMEM exposure reduced Cdx2-positive trophectoderm cell number. After embryo transfer, in vitro culture groups showed increased placental and birth weights compared with natural mating controls, although possible litter/recipient effects should be considered. Under HFD challenge, MEM offspring developed overweight-associated impaired glucose tolerance, M/C offspring showed severe HFD intolerance with body-weight loss and reduced survival, and C/M offspring showed a tendency toward impaired glucose handling without marked overweight. Our findings suggest that the timing and duration of αMEM exposure during preimplantation development influence long-term metabolic phenotypes. Sustained 48 h exposure was associated with the overweight-related phenotype, whereas temporally restricted exposures were associated with different postnatal responses.

PMID:
42893854
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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