Cited by 370Genetic Syndromes and ImprintingReproductive Biology and FertilityBirth, Development, and Health

Long-term effect of in vitro culture of mouse embryos with serum on mRNA expression of imprinting genes, development, and behavior

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Fernández-Gonzalez, Raúl, Moreira, Pedro, Bilbao, Ainhoa, Jiménez, Adela, Pérez-Crespo, Miriam, Ramírez, Miguel Angel, De Fonseca, Fernando Rodríguez, Pintado, Belén +1 more·2004·Proceedings of the National Academy of Sciences

Abstract

The long-term developmental and behavioral consequences of mammalian embryo culture are unknown. By altering the culture medium with the addition of FCS, we wanted to determine whether mouse embryos cultured under suboptimal conditions develop aberrant mRNA expression of imprinting genes at the blastocyst stage and whether fetal development, growth, and behavior of adult mice are affected. One-cell embryos obtained from superovulated female B6CBAF 1 mice were cultured for 4 days in K + -modified simplex optimized medium in the presence of either 10% FCS or 1 g/liter BSA. After embryo transfer, born animals were submitted to several developmental and behavior tests. The mRNA expression of some imprinting genes was significantly affected in blastocysts cultured in the presence of FCS. Two of the eight measures of preweaning development and some specific measures of neuromotor development, such as the walking activity, were delayed in the group originated with FCS. After 34 weeks, the weight of female mice cultured in vitro in the presence of FCS was significantly higher than controls. In addition, the locomotion activity of mice was altered at 5 and 15 months. Anatomopathological and histological analysis of animals at 20 months of age showed some large organs and an increase in pathologies. We have found that mice derived from embryos cultured with FCS exhibited specific behavioral alterations in anxiety and displayed deficiencies in implicit memories. Our data indicate that long-term programming of postnatal development, growth, and physiology can be affected irreversibly during the preimplantation period of embryo development by suboptimal in vitro culture.

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Crossref · 10.1073/pnas.0308560101

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Authors
Fernández-Gonzalez, R., Moreira, P., Bilbao, A., Jiménez, A., Pérez-Crespo, M., Ramírez, M. A., De Fonseca, F. R., Pintado, B., & Gutiérrez-Adán, A.
Affiliations
  • Departamento de Reproducción Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Carretera de la Coruña Km 5.9, 28040 Madrid, Spain; and Fundación Hospital Carlos Haya, Avenida Carlos Haya 82, 29010 Málaga, Spain
  • Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (ES)
Venue
Proceedings of the National Academy of Sciences
Published
2004-04-12
Volume
101
Issue
16
Pages
5880-5885
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2147536097
Cited by
370
References
47
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 8 · 2021: 9 · 2020: 18 · 2019: 12 · 2018: 17 · 2017: 22 · 2016: 16 · 2015: 18 · 2014: 25 · 2013: 11 · 2012: 27
FWCI
13.57
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
embryo culture, fetal bovine serum, genomic imprinting, imprinted genes, blastocyst, preimplantation embryo development, developmental programming, anxiety-like behavior, implicit memory, locomotor activity, growth, organ enlargement
MeSH terms
Animals, Behavior, Animal, Blood, Embryo, Mammalian, Growth, RNA, Messenger, Transcription, Genetic, Genomic Imprinting, Culture Techniques, Mice

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