Arias Álvarez, MaríaAlfonso Gutiérrez-AdanEva PericuestaBermejo Álvarez, PabloMillán Pastor, María PilarMaría RodríguezLorenzo González, Pedro LuisPilar García RebollarGarcía García, Rosa María2026-04-292026-04-292026Arias-Alvarez, M., Gutiérrez-Adan, A., Pericuesta, E., Bermejo-Alvarez, P., Millán, P., Rodríguez, M., Lorenzo, P. L., Rebollar, P. G., & García-García, R. M. (2026). Maternal undernutrition reprograms reproductive and metabolic phenotypes in female offspring of the rabbit model. PloS one, 21(3), e0345066. https://doi.org/10.1371/journal.pone.0345066https://doi.org/10.1371/journal.pone.0345066https://hdl.handle.net/20.500.14352/136434Author contributions Conceptualization: Maria Arias Alvarez, Pedro Luis Lorenzo, Pilar García Rebollar, Rosa Maria Garcia Garcia. Data curation: Maria Arias Alvarez, Pilar García Rebollar, Rosa Maria Garcia Garcia. Formal analysis: Maria Arias Alvarez, Pilar García Rebollar, Rosa Maria Garcia Garcia. Funding acquisition: Maria Arias Alvarez, Pedro Luis Lorenzo, Pilar García Rebollar, Rosa Maria Garcia Garcia. Investigation: Maria Arias Alvarez, Pilar García Rebollar, Rosa Maria Garcia Garcia. Methodology: Maria Arias Alvarez, Alfonso Gutiérrez-Adan, Eva Pericuesta, Pablo Bermejo-Alvarez, Pilar Millán, María Rodríguez, Pedro Luis Lorenzo, Pilar García Rebollar, Rosa Maria Garcia Garcia. Project administration: Maria Arias Alvarez, Rosa Maria Garcia Garcia. Resources: Maria Arias Alvarez, Pilar García Rebollar, Rosa Maria Garcia Garcia. Supervision: Maria Arias Alvarez, Pilar García Rebollar, Rosa Maria Garcia Garcia. Writing – original draft: Maria Arias Alvarez, Pilar García Rebollar, Rosa Maria Garcia Garcia. Writing – review & editing: Maria Arias Alvarez, Alfonso Gutiérrez-Adan, Eva Pericuesta, Pablo Bermejo-Alvarez, Pilar Millán, Pedro Luis Lorenzo, Pilar García Rebollar, Rosa Maria Garcia Garcia.Maternal undernutrition during pregnancy in mammals can induce long-term effects in offspring health through molecular programming of the gametes. Using the rabbit model, this study investigates whether maternal food restriction (FR) during the first two-thirds of gestation induces effects on ovarian follicular, oocyte, and early embryo developmental markers in F1 female offspring at the onset of reproductive life. Additionally, body composition, metabolic profile, and growth trajectory from birth to sexual maturity (16 weeks) were assessed to evaluate potential impacts on overall health. Pregnant females (F0) were fed either ad libitum (Control group) or a restricted diet covering 60% of nutritional requirements (FR group). Offspring from both groups were fed ad libitum. Maternal FR had no significant effects on birth weight and survival of progeny, growth trajectory, feed intake or glycemic profile during the juvenile phase. Body weight, body composition, lipid, and glycemic profiles in F1 sexually mature females were similar. However, serum aminotransferase levels were significantly elevated in the F1 females from FR group (P<0.05) Serum anti-Müllerian hormone levels, ovulation rate, apoptosis rate, and in vitro embryo development did not differ between groups. These findings suggest that re-feeding after maternal food restriction can attenuate adverse long-term effects on offspring growth and metabolism, while modulating the expression of genes related to oxidative stress, apoptosis and fatty acid uptake in the oocytes of F1 females. This modulation may reflect the activation of compensatory intracellular mechanisms that support early embryonic development in juvenile females at the onset of their reproductive lifeengAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1932-6203https://doi.org/10.1371/journal.pone.034506641886523https://pubmed.ncbi.nlm.nih.gov/41886523/open access61:57Ciencias Biomédicas31 Ciencias Agrarias