Demonstration of the deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model
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1
Université Paul Sabatier, Toulouse 3, Laboratoire d'immunogénétique moléculaire (EA3034), France
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2
CHU de Toulouse, Laboratoire d'Immunologie, France
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3
National Institute for Biological Standards and Control, Division of Virology, United Kingdom
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4
Université Paul Sabatier, Toulouse 3, Institut de Mathématiques, France
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 (1). We decided to explore the impact of MHC feto-maternal compatibility on reproduction in a cynomolgus macaque breeding unit composed of animals originating from Mauritius Island. The Mauritian macaque population presents a very restricted MHC polymorphism (only seven founding haplotypes) due to a strong founding bottleneck (2, 3, 4, 5). The MHC polymorphism was investigated in 237 trios (male, female and offspring) using 17 microsatellite markers distributed across the MHC (Figure 1) (6). Haplotypes were confirmed by segregation analysis. We evaluated the relative frequencies of offspring MHC-compatible and MHC-semicompatible with their mother. Among the 237 trios, 106 offsprings were semi-compatible and 47 offsprings were fully compatible with their mother for all MHC markers. This repartition is incompatible with a random distribution with an interval of confidence of 99,9 %. In a second step, we selected 42 trios for which the identity of the father is certain and for which the theoretical probabilities of full compatible and semi-compatible offsprings were equals. We found 11 offsprings fully compatible and 31 offsprings semi-compatible with their respective mother (Figure 2). Again, the observed repartition was clearly outside the interval of confidence of 99 %, and therefore most probably resulted from a selection of the semi-compatible foetuses during pregnancy. We concluded that MHC fully compatible cynomolgus macaque foetuses have a selective survival disadvantage in comparison with foetuses inheriting a paternal MHC haplotype differing from maternal haplotypes. We analysed separately the compatibility of offspring with their mother for MHC class II (5 markers) or MHC class I and III regions (12 markers) in trios for which compatibility and semi-compatibility offspring were equi-probable. For the MHC class II region, among the 87 informative trios, 42 offsprings were full compatible and 45 were semi-compatible with their mother. This repartition does not differ significantly from a random distribution. We deduced that the MHC class II region is not responsible of this selective survival disadvantage of MHC fully compatible foetuses with their mother. For the MHC class I and III region, among the 48 informative trios, only 15 offsprings were full compatible with their mother. This repartition (15-33) is incompatible with a random distribution with an interval of confidence of 98 %. We concluded that the offspring/mother compatibility in the MHC class I and III region, influences the chance of foetus birth. The low density and low polymorphism of markers in MHC class IA, class IB and class III regions did not allow delineating more precisely the most influent region.
References
1. Beydoun H, and Saftlas AF. Association of human leucocyte antigen sharing with recurrent spontaneous abortions. Tissue Antigens (2005) 65(2): 123-35.
2 Bonhomme M, Blancher A, Cuartero S, Chikhi L, and Crouau-Roy B. Origin and number of founders in an introduced insular primate: estimation from nuclear genetic data. Mol Ecol (2008) 17(4): 1009-19.
3. Blancher A, Bonhomme M, Crouau-Roy B, Terao K, Kitano T, and Saitou N. Mitochondrial DNA sequence phylogeny of 4 populations of the widely distributed cynomolgus macaque (Macaca fascicularis fascicularis). J Hered (2008) 99(3): 254-64.
4. Blancher A, Aarnink A, Savy N, and Takahata N. Use of Cumulative Poisson Probability Distribution as an Estimator of the Recombination Rate in an Expanding Population: Example of the Macaca fascicularis Major Histocompatibility Complex. G3 (Bethesda) 2012 2(1): 123-30.
5. Aarnink A, Bonhomme M, and Blancher A. Positive selection in the major histocompatibility complex class III region of cynomolgus macaques (Macaca fascicularis) of the Philippines origin. Tissue Antigens (2013) 81(1): 12-8.
6. Mee ET, Badhan A, Karl JA, Wiseman RW, Cutler K, Knapp LA, Almond N, O'Connor DH, and Rose NJ. MHC haplotype frequencies in a UK breeding colony of Mauritian cynomolgus macaques mirror those found in a distinct population from the same geographic origin. J Med Primatol (2009) 38(1): 1-14.
7. Watanabe A, Shiina T, Shimizu S, Hosomichi K, Yanagiya K, Kita YF, Kimura T,
Soeda E, Torii R, Ogasawara K, Kulski JK, and Inoko H. A BAC-based contig map of the cynomolgus macaque (Macaca fascicularis) major histocompatibility complex genomicregion. Genomics (2007) 89(3): 402-12.
Keywords:
feto-maternal compatibility,
MHC,
microsatellites,
cynomolgus macaque,
captive breeding unit
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Aarnink
A,
Mee
E,
Savy
N,
Rose
N and
Blancher
A
(2013). Demonstration of the deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00904
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Received:
28 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Antoine Blancher, Université Paul Sabatier, Toulouse 3, Laboratoire d'immunogénétique moléculaire (EA3034), Toulouse cedex09, 31059, France, blancher.antoine@neuf.fr