Long-term effect of in vitro culture of mouse embryos with serum on mRNA expression of imprinting genes, development, and behavior
Open accessAbstract
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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In vitro fertilization and ovulation induction can result in abnormal methylation and dysregulation of imprinted genes.
“in vitro fertilization and ovulation induction can result in abnormal methylation and dysregulation of imprinted genes”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [77]
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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
- Publisher
- National Academy of Sciences
- Published
- 2004-04-12
- Volume
- 101
- Issue
- 16
- Pages
- 5880-5885
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC395892
- 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
- green
- europepmc.org
- 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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