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Stress during first gestation of ewes impairs memory and learning of male offspring

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Abstract

This study aimed to investigate the influence of gestational stress induced by lipopolysaccharide (LPS, Escherichia coli) on the physiological changes of ewes, as well as on the subsequent behavioral interaction between ewes and lambs and on the memory and learning of 30-day-old offspring in a T-maze. Thirty-six nulliparous pregnant crossbred Santa Ines ewes with an initial live weight of 45 ± 6 kg, age of 12 ± 2 months, and body condition score between 3 and 3.5 (on a scale of 1 to 5) were divided into two treatments: LPS treatment (E. coli; 0.8 μg.kg−1) and Control (placebo/saline) administered in late pregnancy (day 120). Blood samples were collected before (0 h at 5:00 h) and 1 h, 2 h, 4 h, 8 h, 12 h, 24 h after the administration of LPS or placebo to determine the cortisol release curve. Rectal temperature was measured at the same time points. After birth, male lambs (N = 19) were used to evaluate the maternal-offspring behavioral interaction, weight, and cognitive ability in a T-maze. Blood cortisol and rectal temperature of ewes increased after LPS administration and returned to baseline levels after 24 h. The activities facilitating and stimulating suckling were higher on LPS group (P < 0.05). Lambs whose mothers were challenged with LPS during late pregnancy showed greater learning and memory disabilities including fear behavior and the inability to make decisions at 30 days of age in the T-maze. In sheep, the immunological stress induced by LPS in late pregnancy promotes an inflammatory response characterized by specific rectal temperature and cortisol release profiles, improving maternal care that can increase offspring survival; however, the exposure of sheep fetuses to maternal inflammation causes cognitive impairment in lambs at 30 days of age, which could not be reduced by the behavioral interaction between the mother and offspring.

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Acknowledgements

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo [grant number 2016/17758-1]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [fellowship 0001], and Conselho Nacional de Desenvolvimento Científico e Tecnológico [fellowship 309337/2017-8].

Funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo [grant number 2016/17758-1]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior [fellowship 0001], and Conselho Nacional de Desenvolvimento Científico e Tecnológico [fellowship 309337/2017-8].

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Authors and Affiliations

  1. Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Duque de Caxias Norte Av., 225, Campus Fernando Costa, Pirassununga, SP, 13635-900, Brazil

    F. L. Henrique, H. V. A. Bezerra, H. Z. Polato, A. C. Fernandes, H. B. Hooper, L. F. Pulido-Rodríguez, E. A. L. Titto & C. G. Titto

  2. Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Duque de Caxias Norte Av., 225, Campus Fernando Costa, Pirassununga, SP, 13635-900, Brazil

    A. J. Zanella

  3. Mediterranean Institute for Agriculture, Environment and Development, Universidade de Évora, Apartado 94, 7006-554, Évora, Portugal

    A. M. F. Pereira

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  1. F. L. Henrique
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  2. A. J. Zanella
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  3. H. V. A. Bezerra
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  4. H. Z. Polato
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  5. A. C. Fernandes
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Contributions

Fábio Luís Henrique conceived and designed the study, together with Prof. Cristiane Gonçalves Titto (advisor) and Prof. Adroaldo José Zanella (co-advisor). Fábio Luís Henrique, Cristiane Gonçalves Titto, Helena Viel Alves Bezerra, Heloíse Zavatieri Polato, Arícia Christofaro Fernandes, Lina Pulido-Rodríguez and Henrique Barbosa Hooper acquired the experimental data, which lasted about 7 months. Fábio Luís Henrique, Prof. Cristiane Gonçalves Titto, Prof. Adroaldo José Zanella, Evaldo Titto and Alfredo Pereira performed the analysis and interpretation of the data. Fábio Luís Henrique, Helena Viel Alves Bezerra and Cristiane Gonçalves Titto prepared the manuscript and final draft.

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Correspondence to C. G. Titto.

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All procedures involving animals were in accordance with the Brazilian Law 11.794 of October 8, 2008, Decree 6899 of July 15, 2009, as well as with the rules issued by the National Council for Control of Animal Experimentation (CONCEA), and was approved by the Ethic Committee on Animal Use of the School of Animal Science and Food Engineering—(São Paulo University) (CEUA/FZEA) in the meeting of 10/21/2015 under protocol number 2296210915 at https://www.usp.br/ceuafzea/. Authors supplied detailed information on the ethical treatment of their animals in their submission, using ARRIVE checklist.

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We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who met the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all named authors. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property.

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Henrique, F.L., Zanella, A.J., Bezerra, H.V.A. et al. Stress during first gestation of ewes impairs memory and learning of male offspring. Vet Res Commun 45, 251–260 (2021). https://doi.org/10.1007/s11259-021-09805-3

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