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Deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model

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Abstract

The impact of feto-maternal histocompatibility on reproduction has inspired long-lasting debates. However, after the review of numerous articles, the impact of HLA allele sharing within couples on fecundity remains questionable. We decided to explore the impact of major histocompatibility complex (MHC) feto-maternal compatibility on reproduction in a cynomolgus macaque facility composed of animals of Mauritian descent. The Mauritian-derived macaque population presents a very restricted MHC polymorphism (only seven founding haplotypes) due to a strong founding bottleneck effect. The MHC polymorphism was investigated in 237 trios (male, female and offspring) using 17 microsatellite markers distributed across the MHC. Haplotypes were confirmed by segregation analysis. We evaluated the relative frequencies of MHC-compatible and MHC-semi-compatible offspring with the mothers. Among the 237 trios, we selected 42 trios for which the identity of the father is certain and for which the theoretical probabilities of fully compatible and semi-compatible offspring were equal. We found 11 offspring fully compatible and 31 offspring semi-compatible with their respective mother. The observed proportions were clearly outside the interval of confidence of 99 % and therefore most probably resulted from a selection of the semi-compatible offspring during pregnancy. We concluded that MHC fully compatible cynomolgus macaque offspring have a selective survival disadvantage in comparison with offspring inheriting a paternal MHC haplotype differing from maternal haplotypes.

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Acknowledgments

EM and NR were funded in part by the NIHR Centre for Research in Health Protection at the Health Protection Agency. AA, NC, NS and AB were funded in part by the French Ministry of Research (EA3034 contract) and University Paul Sabatier from Toulouse. We are pleased to thank Audrey Dauba and Sylvie Hébrard for their excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratoire d’Immunogénétique Moléculaire, EA 3034, Faculté de Médecine Purpan, Université Paul Sabatier, Toulouse 3, CHU de Toulouse, Toulouse, France

    Alice Aarnink, Nicolas Congy-Jolivet & Antoine Blancher

  2. Division of Virology, National Institute for Biological Standards and Control, Medicines and Healthcare Products Regulatory Agency, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK

    Edward T. Mee & Nicola J. Rose

  3. Institut de Mathématiques de Toulouse (IMT), Université Paul Sabatier, Toulouse 3, Toulouse, France

    Nicolas Savy

  4. Laboratoire d’Immunologie, Hôpital Rangueil, 1 avenue Jean Poulhes, TSA 50032, 31059, Toulouse Cedex 9, France

    Antoine Blancher

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  1. Alice Aarnink
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  2. Edward T. Mee
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  3. Nicolas Savy
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  4. Nicolas Congy-Jolivet
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  5. Nicola J. Rose
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  6. Antoine Blancher
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Correspondence to Antoine Blancher.

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Aarnink, A., Mee, E.T., Savy, N. et al. Deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model. Immunogenetics 66, 105–113 (2014). https://doi.org/10.1007/s00251-013-0752-3

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