FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Proceedings. Biological sciences2017; 284(1868); 20171824; doi: 10.1098/rspb.2017.1824

Major histocompatibility complex-linked social signalling affects female fertility.

Abstract: Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses () to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males ( = 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling.
© 2017 The Author(s).
Get Full Text
Publication Date: 2017-12-08 PubMed ID: 29212724PubMed Central: PMC5740280DOI: 10.1098/rspb.2017.1824Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study demonstrates the role of major histocompatibility complex (MHC) genes in social signalling and mate preferences in horses. It further illustrates that exposure to MHC-dissimilar males around the time of conception increases the probability of female horses getting pregnant. This suggests that early pregnancy failures might be attributed to life-history decisions made by the female horses, guided by MHC-linked social signalling.

Major Histocompatibility Complex (MHC)

  • The MHC is a set of genes involved in immune system regulation. Their function extends to social communication and mate choice in many species, inclusive of humans.
  • Interestingly, as per the results of this research, it now appears they might also influence female fertility.

Experimental Design and Testing

  • 191 female horses participated in this experiment where they were exposed to either an MHC-similar or an MHC-dissimilar male during their ovulation period.
  • To rule out the influence of non-MHC-linked male characteristics, a within-subject experimental design was used.
  • Moreover, the insemination was controlled instrumentally with sperm of other males (106 individuals), to avoid the effects of specific semen or embryo traits.

Key Findings

  • The study found that the likelihood of getting pregnant increased in females exposed to an MHC-dissimilar male in comparison to those exposed to an MHC-similar male.
  • The overall genetic difference with respect to the stimulus males, determined based on microsatellite markers on 20 chromosomes, did not show any impact on the results.
  • This suggests an intriguing hypothesis wherein early pregnancy failures could be attributed to ‘cryptic female choice’; that is, secretive life-history choices made by the female, conditioned by MHC-linked social signals.

Conclusion

  • This research lends significant understanding of the role MHC genes might play in reproductive success beyond choosing a suitable mate.
  • They apparently influence biological and behavioural responses in females, impacting life-history decisions leading to more effective reproductive outcomes.

Cite This Article

APA
Burger D, Thomas S, Aepli H, Dreyer M, Fabre G, Marti E, Sieme H, Robinson MR, Wedekind C. (2017). Major histocompatibility complex-linked social signalling affects female fertility. Proc Biol Sci, 284(1868), 20171824. https://doi.org/10.1098/rspb.2017.1824

Publication

Proceedings. Biological sciences
ISSN: 1471-2954
NlmUniqueID: 101245157
Country: England
Language: English
Volume: 284
Issue: 1868
PII: 20171824

Researcher Affiliations

Burger, D
  • Swiss Institute of Equine Medicine, Agroscope and University of Berne, 1580 Avenches, Switzerland.
Thomas, S
  • Swiss Institute of Equine Medicine, Agroscope and University of Berne, 1580 Avenches, Switzerland.
Aepli, H
  • Swiss Institute of Equine Medicine, Agroscope and University of Berne, 1580 Avenches, Switzerland.
Dreyer, M
  • Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne, Switzerland.
Fabre, G
  • Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne, Switzerland.
Marti, E
  • Department of Clinical Research, Vetsuisse Faculty, University of Berne, 3012 Bern, Switzerland.
Sieme, H
  • Clinic for Horses, Unit for Reproductive Medicine, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
Robinson, M R
  • Department of Computational Biology, Genopode, University of Lausanne, 1015 Lausanne, Switzerland.
Wedekind, C
  • Department of Ecology and Evolution, Biophore, University of Lausanne, 1015 Lausanne, Switzerland claus.wedekind@unil.ch.

MeSH Terms

  • Animals
  • Female
  • Fertility
  • Horses / physiology
  • Major Histocompatibility Complex
  • Mating Preference, Animal
  • Reproduction

Conflict of Interest Statement

We declare we have no competing interests.

References

This article includes 52 references
  1. Davies DM. 2013. The compatibility gene. London, UK: Allen Lane.
  2. Ruff JS, Nelson AC, Kubinak JL, Potts WK. MHC signaling during social communication.. Adv Exp Med Biol 2012;738:290-313.
    doi: 10.1007/978-1-4614-1680-7_17pmc: PMC4835215pubmed: 22399386google scholar: lookup
  3. Milinski M, Croy I, Hummel T, Boehm T. Major histocompatibility complex peptide ligands as olfactory cues in human body odour assessment.. Proc Biol Sci 2013 Mar 22;280(1755):20122889.
    doi: 10.1098/rspb.2012.2889pmc: PMC3574394pubmed: 23345577google scholar: lookup
  4. Kromer J, Hummel T, Pietrowski D, Giani AS, Sauter J, Ehninger G, Schmidt AH, Croy I. Influence of HLA on human partnership and sexual satisfaction.. Sci Rep 2016 Aug 31;6:32550.
    doi: 10.1038/srep32550pmc: PMC5006172pubmed: 27578547google scholar: lookup
  5. Burger D, Dolivo G, Marti E, Sieme H, Wedekind C. Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus).. Proc Biol Sci 2015 May 22;282(1807):20150407.
    doi: 10.1098/rspb.2015.0407pmc: PMC4424655pubmed: 25904670google scholar: lookup
  6. Burger D, Meuwly C, Marti E, Sieme H, Oberthür M, Janda J, Meinecke-Tillmann S, Wedekind C. MHC-correlated preferences in diestrous female horses (Equus caballus).. Theriogenology 2017 Feb;89:318-323.e1.
    doi: 10.1016/j.theriogenology.2016.09.015pubmed: 27842717google scholar: lookup
  7. Kamiya T, O'Dwyer K, Westerdahl H, Senior A, Nakagawa S. A quantitative review of MHC-based mating preference: the role of diversity and dissimilarity.. Mol Ecol 2014 Nov;23(21):5151-63.
    doi: 10.1111/mec.12934pubmed: 25251264google scholar: lookup
  8. Winternitz J, Abbate JL, Huchard E, Havlíček J, Garamszegi LZ. Patterns of MHC-dependent mate selection in humans and nonhuman primates: a meta-analysis.. Mol Ecol 2017 Jan;26(2):668-688.
    doi: 10.1111/mec.13920pubmed: 27859823google scholar: lookup
  9. Leclaire S, Strandh M, Mardon J, Westerdahl H, Bonadonna F. Odour-based discrimination of similarity at the major histocompatibility complex in birds.. Proc Biol Sci 2017 Jan 11;284(1846).
    doi: 10.1098/rspb.2016.2466pmc: PMC5247505pubmed: 28077776google scholar: lookup
  10. Leinders-Zufall T, Brennan P, Widmayer P, S PC, Maul-Pavicic A, Jäger M, Li XH, Breer H, Zufall F, Boehm T. MHC class I peptides as chemosensory signals in the vomeronasal organ.. Science 2004 Nov 5;306(5698):1033-7.
    doi: 10.1126/science.1102818pubmed: 15528444google scholar: lookup
  11. Milinski M, Griffiths S, Wegner KM, Reusch TB, Haas-Assenbaum A, Boehm T. Mate choice decisions of stickleback females predictably modified by MHC peptide ligands.. Proc Natl Acad Sci U S A 2005 Mar 22;102(12):4414-8.
    doi: 10.1073/pnas.0408264102pmc: PMC555479pubmed: 15755811google scholar: lookup
  12. Spehr M, Kelliher KR, Li XH, Boehm T, Leinders-Zufall T, Zufall F. Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands.. J Neurosci 2006 Feb 15;26(7):1961-70.
    doi: 10.1523/jneurosci.4939-05.2006pmc: PMC6674934pubmed: 16481428google scholar: lookup
  13. Penn DJ, Potts WK. The Evolution of Mating Preferences and Major Histocompatibility Complex Genes.. Am Nat 1999 Feb;153(2):145-164.
    doi: 10.1086/303166pubmed: 29578757google scholar: lookup
  14. Wedekind C, Walker M, Little TJ. The course of malaria in mice: major histocompatibility complex (MHC) effects, but no general MHC heterozygote advantage in single-strain infections.. Genetics 2005 Jul;170(3):1427-30.
    doi: 10.1534/genetics.105.040683pmc: PMC1451180pubmed: 15911576google scholar: lookup
  15. Penn DJ, Damjanovich K, Potts WK. MHC heterozygosity confers a selective advantage against multiple-strain infections.. Proc Natl Acad Sci U S A 2002 Aug 20;99(17):11260-4.
    doi: 10.1073/pnas.162006499pmc: PMC123244pubmed: 12177415google scholar: lookup
  16. McClelland EE, Penn DJ, Potts WK. Major histocompatibility complex heterozygote superiority during coinfection.. Infect Immun 2003 Apr;71(4):2079-86.
    doi: 10.1128/IAI.71.4.2079-2086.2003pmc: PMC152037pubmed: 12654829google scholar: lookup
  17. Løvlie H, Gillingham MA, Worley K, Pizzari T, Richardson DS. Cryptic female choice favours sperm from major histocompatibility complex-dissimilar males.. Proc Biol Sci 2013 Oct 22;280(1769):20131296.
    doi: 10.1098/rspb.2013.1296pmc: PMC3768299pubmed: 24004935google scholar: lookup
  18. Firman RC, Gasparini C, Manier MK, Pizzari T. Postmating Female Control: 20 Years of Cryptic Female Choice.. Trends Ecol Evol 2017 May;32(5):368-382.
    doi: 10.1016/j.tree.2017.02.010pmc: PMC5511330pubmed: 28318651google scholar: lookup
  19. Wedekind C, Chapuisat M, Macas E, Rülicke T. Non-random fertilization in mice correlates with the MHC and something else.. Heredity (Edinb) 1996 Oct;77 ( Pt 4):400-9.
    doi: 10.1038/hdy.1996.160pubmed: 8885381google scholar: lookup
  20. Firman RC, Simmons LW. Gametic interactions promote inbreeding avoidance in house mice.. Ecol Lett 2015 Sep;18(9):937-43.
    doi: 10.1111/ele.12471pubmed: 26154782google scholar: lookup
  21. Rülicke T, Chapuisat M, Homberger FR, Macas E, Wedekind C. MHC-genotype of progeny influenced by parental infection.. Proc Biol Sci 1998 Apr 22;265(1397):711-6.
    doi: 10.1098/rspb.1998.0351pmc: PMC1689024pubmed: 9608731google scholar: lookup
  22. Stearns SC. Evolutionary medicine: its scope, interest and potential.. Proc Biol Sci 2012 Nov 7;279(1746):4305-21.
    doi: 10.1098/rspb.2012.1326pmc: PMC3479795pubmed: 22933370google scholar: lookup
  23. Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE, Armstrong EG, Nisula BC. Incidence of early loss of pregnancy.. N Engl J Med 1988 Jul 28;319(4):189-94.
    doi: 10.1056/nejm198807283190401pubmed: 3393170google scholar: lookup
  24. Ober C, Elias S, Kostyu DD, Hauck WW. Decreased fecundability in Hutterite couples sharing HLA-DR.. Am J Hum Genet 1992 Jan;50(1):6-14.
    pmc: PMC1682532pubmed: 1729895
  25. Hedrick PW, Thomson G. Evidence for balancing selection at HLA.. Genetics 1983 Jul;104(3):449-56.
    pmc: PMC1202087pubmed: 6884768doi: 10.1093/genetics/104.3.449google scholar: lookup
  26. Newcombe J. 2011. Human chorionic gonadotropin. In Equine reproduction (eds McKinnon AO, Squires EL, Vaala WE, Varner DD), pp. 1804–1810, 2nd edn Chichester, UK: Wiley-Blackwell.
  27. Betteridge KJ. Equine embryology: an inventory of unanswered questions.. Theriogenology 2007 Sep 1;68 Suppl 1:S9-21.
    doi: 10.1016/j.theriogenology.2007.04.037pubmed: 17532037google scholar: lookup
  28. McCue PM, McKinnon AO. 2011. Pregnancy examination. In Equine reproduction (eds McKinnon AO, Squires EL, Vaala WE, Varner DD), pp. 2245–2261, 2nd edn Chichester, UK: Wiley-Blackwell.
  29. Wang J. An estimator for pairwise relatedness using molecular markers.. Genetics 2002 Mar;160(3):1203-15.
    pmc: PMC1462003pubmed: 11901134doi: 10.1093/genetics/160.3.1203google scholar: lookup
  30. Kraemer P, Gerlach G. Demerelate: calculating interindividual relatedness for kinship analysis based on codominant diploid genetic markers using R.. Mol Ecol Resour 2017 Nov;17(6):1371-1377.
    doi: 10.1111/1755-0998.12666pubmed: 28281323google scholar: lookup
  31. R Development Core Team. 2011. nR: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. See http://www.r-project.org/.
  32. Bates D, Maechler M, Bolker B. n2011. nlme4: linear mixed-effects models using S4 classes. R package version 0.999375-39 See http://lme4.r-forge.r-project.org.
  33. Bowling AT, Touchberry RW. Parentage of Great-Basin feral horses. J. Wildl. Manag. 54, 424–429.
    doi: 10.2307/3809652google scholar: lookup
  34. Linklater WL, Cameron EZ. Social dispersal but with philopatry reveals incest avoidance in a polygynous ungulate. Anim. Behav. 77, 1085–1093.
    doi: 10.1006/anbe.1999.1155google scholar: lookup
  35. Boyd L, Keiper R. 2005. Behavioral ecology of feral horses. In The domestic horse: the origins, development, and management of its behaviour (eds Mills DS, McDonnell SM), pp. 55–82. Cambridge, UK: Cambridge University Press.
  36. Pischedda A, Rice WR. Partitioning sexual selection into its mating success and fertilization success components.. Proc Natl Acad Sci U S A 2012 Feb 7;109(6):2049-53.
    doi: 10.1073/pnas.1110841109pmc: PMC3277537pubmed: 22308337google scholar: lookup
  37. Cameron EZ, Linklater WL. Extreme sex ratio variation in relation to change in condition around conception.. Biol Lett 2007 Aug 22;3(4):395-7.
    doi: 10.1098/rsbl.2007.0089pmc: PMC2390657pubmed: 17439844google scholar: lookup
  38. Bartos L, Bartosova J, Pluhacek J, Sindelarova J. Promiscuous behaviour disrupts pregnancy block in domestic horse mares. Behav. Ecol. Sociobiol. 65, 1567–1572.
    doi: 10.1007/s00265-011-1166-6google scholar: lookup
  39. Roberts SC, Gosling LM. Genetic similarity and quality interact in mate choice decisions by female mice.. Nat Genet 2003 Sep;35(1):103-6.
    doi: 10.1038/ng1231pubmed: 12937417google scholar: lookup
  40. Sherborne AL, Thom MD, Paterson S, Jury F, Ollier WE, Stockley P, Beynon RJ, Hurst JL. The genetic basis of inbreeding avoidance in house mice.. Curr Biol 2007 Dec 4;17(23):2061-6.
    doi: 10.1016/j.cub.2007.10.041pmc: PMC2148465pubmed: 17997307google scholar: lookup
  41. Yamazaki K, Beauchamp GK, Wysocki CJ, Bard J, Thomas L, Boyse EA. Recognition of H-2 types in relation to the blocking of pregnancy in mice.. Science 1983 Jul 8;221(4606):186-8.
    doi: 10.1126/science.6857281pubmed: 6857281google scholar: lookup
  42. BRUCE HM. An exteroceptive block to pregnancy in the mouse.. Nature 1959 Jul 11;184:105.
    doi: 10.1038/184105a0pubmed: 13805128google scholar: lookup
  43. Marashi V, Rülicke T. The Bruce effect in Norway rats.. Biol Reprod 2012 Jan;86(1):1-5.
    doi: 10.1095/biolreprod.111.093104pubmed: 21957190google scholar: lookup
  44. Roberts EK, Lu A, Bergman TJ, Beehner JC. A Bruce effect in wild geladas.. Science 2012 Mar 9;335(6073):1222-5.
    doi: 10.1126/science.1213600pubmed: 22362878google scholar: lookup
  45. Hausfater G, Hrdy SB. 2008. Infanticide: comparative and evolutionary perspectives. New York, NY: Aldine.
  46. Berger J. Induced abortion and social factors in wild horses.. Nature 1983 May 5-11;303(5912):59-61.
    doi: 10.1038/303059a0pubmed: 6682487google scholar: lookup
  47. Pluhácek J, Bartos L. Male infanticide in captive plains zebra, Equus burchelli.. Anim Behav 2000 Apr;59(4):689-694.
    doi: 10.1006/anbe.1999.1371pubmed: 10792924google scholar: lookup
  48. Rülicke T, Guncz N, Wedekind C. Early maternal investment in mice: no evidence for compatible-genes sexual selection despite hybrid vigor.. J Evol Biol 2006 May;19(3):922-8.
    doi: 10.1111/j.1420-9101.2005.01039.xpubmed: 16674588google scholar: lookup
  49. Vanderwall DK. Early embryonic loss in the mare. J. Equine Vet. Sci. 28, 691–702.
    doi: 10.1016/j.jevs.2008.10.001google scholar: lookup
  50. Beydoun H, Saftlas AF. Association of human leucocyte antigen sharing with recurrent spontaneous abortions.. Tissue Antigens 2005 Feb;65(2):123-35.
    doi: 10.1111/j.1399-0039.2005.00367.xpubmed: 15713211google scholar: lookup
  51. Meuleman T, Lashley LE, Dekkers OM, van Lith JM, Claas FH, Bloemenkamp KW. HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis.. Hum Immunol 2015 May;76(5):362-73.
    doi: 10.1016/j.humimm.2015.02.004pubmed: 25700963google scholar: lookup
  52. Burger D, Thomas S, Aepli H, Dreyer M, Fabre G, Marti E, Sieme H, Robinson MR, Wedekind C. Major histocompatibility complex-linked social signalling affects female fertility.. Proc Biol Sci 2017 Dec 6;284(1868).
    doi: 10.5061/dryad.04k5qpmc: PMC5740280pubmed: 29212724google scholar: lookup

Citations

This article has been cited 12 times.
  1. Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T. High-Resolution Genotyping of Expressed Equine MHC Reveals a Highly Complex MHC Structure. Genes (Basel) 2023 Jul 10;14(7).
    doi: 10.3390/genes14071422pubmed: 37510326google scholar: lookup
  2. Auer KE, Primus J, Istel S, Dahlhoff M, Rülicke T. Mate genetic similarity affects mating behaviour but not maternal investment in mice. Sci Rep 2023 Jun 29;13(1):10536.
    doi: 10.1038/s41598-023-37547-6pubmed: 37386286google scholar: lookup
  3. Miyamae J, Okano M, Katakura F, Kulski JK, Moritomo T, Shiina T. Large-Scale Polymorphism Analysis of Dog Leukocyte Antigen Class I and Class II Genes (DLA-88, DLA-12/88L and DLA-DRB1) and Comparison of the Haplotype Diversity between Breeds in Japan. Cells 2023 Mar 6;12(5).
    doi: 10.3390/cells12050809pubmed: 36899945google scholar: lookup
  4. Ando A, Matsubara T, Suzuki S, Imaeda N, Takasu M, Shigenari A, Miyamoto A, Ohshima S, Kametani Y, Shiina T, Kulski JK, Kitagawa H. Genetic Association between Farrowing Rates and Swine Leukocyte Antigen Alleles or Haplotypes in Microminipigs. Cells 2022 Oct 5;11(19).
    doi: 10.3390/cells11193138pubmed: 36231100google scholar: lookup
  5. Tang Y, Liu G, Zhao S, Li K, Zhang D, Liu S, Hu D. Major Histocompatibility Complex (MHC) Diversity of the Reintroduction Populations of Endangered Przewalski's Horse. Genes (Basel) 2022 May 23;13(5).
    doi: 10.3390/genes13050928pubmed: 35627313google scholar: lookup
  6. Huang W, Pemberton JM. Within-trio tests provide little support for post-copulatory selection on major histocompatibility complex haplotypes in a free-living population. Proc Biol Sci 2021 Feb 24;288(1945):20202862.
    doi: 10.1098/rspb.2020.2862pubmed: 33622127google scholar: lookup
  7. Murray DR, Moran JB, Prokosch ML, Kerry N. No evidence for a relationship between MHC heterozygosity and life history strategy in a sample of North American undergraduates. Sci Rep 2020 Jun 23;10(1):10140.
    doi: 10.1038/s41598-020-67406-7pubmed: 32576939google scholar: lookup
  8. Grogan KE, Harris RL, Boulet M, Drea CM. Genetic variation at MHC class II loci influences both olfactory signals and scent discrimination in ring-tailed lemurs. BMC Evol Biol 2019 Aug 22;19(1):171.
    doi: 10.1186/s12862-019-1486-0pubmed: 31438845google scholar: lookup
  9. Wedekind C. A predicted interaction between odour pleasantness and intensity provides evidence for major histocompatibility complex social signalling in women. Proc Biol Sci 2018 May 16;285(1878).
    doi: 10.1098/rspb.2017.2714pubmed: 29743250google scholar: lookup
  10. Burger D, Meuwly C, Thomas S, Sieme H, Oberthür M, Wedekind C, Meinecke-Tillmann S. Cycle-specific female preferences for visual and non-visual cues in the horse (Equus caballus). PLoS One 2018;13(2):e0191845.
    doi: 10.1371/journal.pone.0191845pubmed: 29466358google scholar: lookup
  11. Wilkinson LRB, Try H, Robertson SA, Brooks RC, Garratt M. Prior mating without fertilization increases subsequent litter size in mice. Biol Lett 2025 Apr;21(4):20240659.
    doi: 10.1098/rsbl.2024.0659pubmed: 40199343google scholar: lookup
  12. Ando A, Matsubara T, Suzuki S, Imaeda N, Takasu M, Shigenari A, Miyamoto A, Ohshima S, Kametani Y, Shiina T, Kulski JK, Kitagawa H. Genetic Links between Reproductive Traits and Amino Acid Pairwise Distances of Swine Leukocyte Antigen Alleles among Mating Partners in Microminipigs. Int J Mol Sci 2024 Jul 4;25(13).
    doi: 10.3390/ijms25137362pubmed: 39000468google scholar: lookup
Subscribe to our newsletter
Join 99,928 horse owners like you who receive our email updates on horse health and nutrition.