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Supplementation of culture medium with quercetin improves mouse blastocyst quality and increases the expression of HIF-1α protein

Published online by Cambridge University Press:  27 February 2023

Nuria Hernández-Rollán*
Assisted Reproduction Unit, Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain Cryopreservation Facility, Instituto de Biomedicina de Sevilla (IBIs), Seville, Spain
Soledad Sánchez-Mateos
Assisted Reproduction Unit, Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain
Marta López-Morató
Assisted Reproduction Unit, Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain Genetics Unit, Hospital HLA Vistahermosa, Alicante, Spain
Francisco M. Sánchez-Margallo
Assisted Reproduction Unit, Centro de Cirugía de Mínima Invasión Jesús Usón, Cáceres, Spain
Ignacio S. Álvarez*
Department of Cell Biology, Universidad de Extremadura, Badajoz, Spain Instituto Extremeño de Reproducción Asistida (IERA), Badajoz, Spain
Author for correspondence: Nuria Hernández-Rollán. Centro de cirugía de mínima invasión Jesús Usón. C/ Carretera N-521, Km 41.8, 10071, Cáceres, Spain. E-mail: Ignacio S. Álvarez. Dpto. Biología Celular, Facultad de Medicina, Universidad de Extremadura, 06071, Badajoz, Spain. E-mail:
Author for correspondence: Nuria Hernández-Rollán. Centro de cirugía de mínima invasión Jesús Usón. C/ Carretera N-521, Km 41.8, 10071, Cáceres, Spain. E-mail: Ignacio S. Álvarez. Dpto. Biología Celular, Facultad de Medicina, Universidad de Extremadura, 06071, Badajoz, Spain. E-mail:


Regarding the low number of embryos that reach the blastocyst stage when cultured in vitro, this study aimed to evaluate the effects of quercetin on pre-implantation mouse (Mus musculus) embryos obtained using in vitro fertilization, especially during the passage from morula to blastocyst. Furthermore, we studied whether quercetin also affected the expression of hypoxia-inducible factor 1α (HIF-1α). The culture medium for the embryos was supplemented with quercetin, for long or short periods of time, and then the development potential, total cell number, apoptosis rates and expression of HIF-1α were studied to determine the effect of quercetin. Embryos failed to develop when cultured for long periods of time with quercetin, implying the possible toxic effects of this, alternatively antioxidant, compound. However, a short culture from morula to blastocyst significantly improved the development potential of in vitro produced embryos, increasing the final total cell number and reducing the apoptosis rate, observing similar results to those embryos cultured in low-oxygen concentrations or developed in utero. Furthermore, in embryos treated with quercetin for 2 or 4 h we found an increase in HIF-1α compared with untreated embryos. This work could imply a way to use quercetin in fertility clinics to improve the production of healthy blastocysts and, consequently, increase the success rates in assisted reproduction techniques.

Research Article
© The Author(s), 2023. Published by Cambridge University Press

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