Impact of TGF-β and ERK1/2 inhibition on preimplantation embryo development and quality

Articles in Press

Document Type : Original Article

Authors

1 Faculty of Development of Biology, University of Science and Culture, Tehran, Iran

2 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

3 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

4 Department of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute Academic Center for Education, Culture and Research (ACECR), Tehran, Iran

5 Department of Biostatistics and Epidemiology, School of Health, Guilan University of Medical Sciences, Rasht, Iran

10.22038/ijbms.2026.89761.19359

Abstract

Objective(s): Preimplantation embryo culture is a critical phase in assisted reproductive technologies. The use of small molecules to modulate signaling pathways has emerged as a strategy to improve embryo viability. SB431542 inhibits the TGF-β pathway, while PD0325901 inhibits the MEK/ERK pathway. This study investigates whether their combined application affects embryonic development and cellular composition during early culture, independent of stem cell derivation.
Materials and Methods: To assess the effects of SB431542 and PD0325901 on early embryo development, mouse embryos at 2PN, two-cell, and eight-cell stages were collected in vivo and cultured in LIF-supplemented medium containing both molecules until the blastocyst stage. Embryo quality, apoptosis, and developmental progression were assessed using differential staining, TUNEL assay, and continuous monitoring throughout the culture period.
Results: Embryos treated with SB431542 and PD0325901 showed a slightly higher rate of blastocyst formation than controls, though the difference was not statistically significant. Degeneration and apoptosis rates were also comparable between groups. However, treated embryos exhibited a significant reduction in ICM cells at early stages, suggesting compromised inner cell mass development. These findings indicate that dual inhibition may not enhance embryo quality under the tested conditions.
Conclusion: SB431542 and PD0325901, when applied during preimplantation embryo culture, do not significantly improve developmental progression or reduce degeneration and apoptosis. The observed decrease in ICM cells suggests limited benefit for embryo culture protocols designed to support early development. Further studies are needed to evaluate their relevance in stem cell derivation contexts.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 24 February 2026

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