Sexual Reproduction and Immunity


Sexual reproduction is a highly complicated process shaped in part by the need to optimise reproductive investment, which can differ and evolve antagonistically between the sexes. Sexual reproduction is also intimately linked with immunity through a variety of means. Combining these seemingly disparate biological functions has led to the emergence of the new field of reproductive immunity. One striking parallel between reproduction and immunity is the detection of ‘other’. Failure to detect pathogens results in disease. Failure to ignore self causes autoimmunity. Similarly, individuals, as well as gametes, must choose appropriate partners avoiding interspecific mating on one extreme or reproducing with kin to avoid inbreeding, on the other. The relationship between reproduction and immunity is likely affected by the mating system and the degree of sexual conflict. Reproduction and immunity seem connected in three ways by resource trade‐offs among life‐history traits, by disease reduction due to mate choice of healthy mates and protective genes for the offspring and by mating‐induced immunity to reduce infection risk.

Key Concepts

  • Mating and sexual reproduction can be linked to immunity in three ways:
    • Reproduction and immunity can trade‐off.
    • Choosing a healthy partner can result in protection for the actor and its offspring.
    • Mating can directly result in immune responses.
  • This immune activation may be a much older association between the immune system and sexual reproduction.
  • Both immune activation and sexual reproduction involve recognising self from nonself.
  • Immune responses upon mating can serve to protect females from infection and play a role in sperm selection.
  • Mating system likely dictates the intensity and costs of these immune responses on mating.

Keywords: genital microbes; immunity to sperm; reproductive organs; sexually transmitted infections; gamete recognition


Adamo SA (2008a) Bidirectional connections between the immune system and the nervous system in insects. In: Beckage NE (ed.) Insect Immunology, pp 129–149. Academic Press: San Diego.

Adamo SA (2008b) Norepinephrine and octopamine: linking stress and immune function across phyla. Invertebrate Survival Journal 5: 12–19.

Adamo SA (2014) The effects of stress hormones on immune function may be vital for the adaptive reconfiguration of the immune system during fight‐or‐flight behavior. Integrative and Comparative Biology 54: 419–426. DOI: 10.1093/icb/icu005.

Afzelius BA , Alberti G , Godula DJ and Witalinski W (1989) Virus‐ and Rickettsia‐infected sperm cells in arthropods. Journal of Invertebrate Pathology 53: 365–377.

Andersson MB (1994) Sexual Selection. Princeton University Press: Princeton.

Antonovics J (2005) Plant venereal diseases: insights from a messy metaphor. The New Phytologist 165: 71–80. DOI: 10.1111/j.1469‐8137.2004.01215.x.

Barribeau S and Schmid‐Hempel P (2017) Sexual healing: mating induces a protective immune response in bumblebees. Journal of Evolutionary Biology 30: 202–209. DOI: 10.1111/jeb.12964.

Bellinvia S , Johnston PR , Mbedi S and Otti O (2019) Mating changes the genital microbiome in both sexes of the common bedbug Cimex lectularius across populations. bioRxiv: 819300. DOI: 10.1101/819300.

Bellinvia S , Johnston PR , Reinhardt K and Otti O (2020) Bacterial communities of the reproductive organs of virgin and mated common bedbugs Cimex lectularius . Ecological Entomology. DOI: 10.1111/een.12784.

Birkhead TR and Møller AP (1998) Sperm competition, sexual selection and different routes to fitness. In: Birkhead TR and Møller AP (eds) Sperm Competition and Sexual Selection, pp 1–10. Academic Press: San Diego.

Blaxter M and Sunnucks P (2011) Velvet worms. Current Biology 21: R268–R240. DOI: 10.1016/j.cub.2011.02.017.

Boehm T (2006a) Quality control in self/nonself discrimination. Cell 125: 845–858. DOI: 10.1016/j.cell.2006.05.017.

Boehm T (2006b) Co‐evolution of a primordial peptide‐presentation system and cellular immunity. Nature Reviews Immunology 6: 79–84. DOI: 10.1038/nri1749.

Boots M , Donnelly R and White A (2013) Optimal immune defence in the light of variation in lifespan. Parasite Immunology 35: 331338. DOI: 10.1111/pim.12055.

Boots M and Best A (2018) The evolution of constitutive and induced defences to infectious disease. Proceedings of the Royal Society of London B 285: 20180658. DOI: 10.1098/rspb.2018.0658.

Bretscher P and Cohn M (1970) A theory of self‐nonself discrimination. Science 169: 1042–1049. DOI: 10.1126/science.169.3950.1042.

Broderick NA , Welchman DP and Lemaitre B (2009) Recognition and response to microbial infection in Drosophila . In: Rolff J and Reynolds SE (eds) Insect Infection and Immunity, pp 13–33. Oxford University Press: Oxford.

Brown MJ , Schmid‐Hempel R and Schmid‐Hempel P (2003) Strong context‐dependent virulence in a host–parasite system: reconciling genetic evidence with theory. The Journal of Animal Ecology 72: 994–1002. DOI: 10.1046/j.1365‐2656.2003.00770.x.

Chae E , Bomblies K , Kim S‐T , et al. (2014) Species‐wide genetic incompatibility analysis identifies immune genes as hotspots of deleterious epistasis. Cell 159: 1341–1351. DOI: 10.1016/j.cell.2014.10.049.

Chen C , Song X , Wei W , et al. (2017) The microbiota continuum along the female reproductive tract and its relation to uterine‐related diseases. Nature Communications 8: 875. DOI: 10.1038/s41467‐017‐00901‐0.

Clarke GN (2009) Etiology of sperm immunity in women. Fertility and Sterility 91: 639–643. DOI: 10.1016/j.fertnstert.2007.11.045.

Clutton‐Brock TH and Huchard E (2013) Social competition and selection in males and females. Philosophical Transactions of the Royal Society B 368: 20130074. DOI: 10.1098/rstb.2013.0074.

Drobnis EZ and Overstreet JW (1992) The natural history of spermatozoa in the female reproductive tract. Oxford Reviews of Reproductive Biology 14: 1–45.

Eberhard WG (1996) Female Control: Sexual selection and Cryptic Female Choice. Princeton University Press: Princeton.

Firman RC , Gasparini C , Manier MK and Pizzari T (2017) Postmating female control: 20 years of cryptic female choice. Trends in Ecology & Evolution 32: 368–382. DOI: 10.1016/j.tree.2017.02.010.

Flatt T , Tu M‐P and Tatar M (2005) Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. BioEssays 27: 999–1010. DOI: 10.1002/bies.20290.

Flatt T , Heyland A , Rus F , et al. (2008) Hormonal regulation of the humoral innate immune response in Drosophila melanogaster . The Journal of Experimental Biology 211: 2712–2724. DOI: 10.1242/jeb.014878.

Ghaderi D , Springer SA , Ma F , et al. (2011) Sexual selection by female immunity against paternal antigens can fix loss of function alleles. Proceedings of the National Academy of Sciences of the United States of America 108: 17743–17748. DOI: 10.1073/pnas.1102302108.

González‐Marín C , Roy R , López‐Fernández C , et al. (2011) Bacteria in bovine semen can increase sperm DNA fragmentation rates: a kinetic experimental approach. Anim. Reprod. Sci. 123: 139–148. DOI: 10.1016/j.anireprosci.2010.11.014.

Gwynne DT (2008) Sexual conflict over nuptial gifts in insects. Annual Review of Entomology 53: 83–101. DOI: 10.1146/annurev.ento.53.103106.093423.

Hamilton DG , Jones ME , Cameron EZ , et al. (2019) Rate of intersexual interactions affects injury likelihood in Tasmanian devil contact networks. Behavioral Ecology 30: 1087–1095. DOI: 10.1093/beheco/arz054.

Hangartner S , Michalczyk L , Gage MJG and Martin OY (2015) Experimental removal of sexual selection leads to decreased investment in an immune component in female Tribolium castaneum. Infection, Genetics and Evolution 33: 212–218. DOI: 10.1016/j.meegid.2015.05.005.

Hart MW , Stover DA , Guerra V , et al. (2018) Positive selection on human gamete‐recognition genes. PeerJ 6: e4259. DOI: 10.7717/peerj.4259.

He J , Ma L , Kim S , Nakai J and Yu CR (2008) Encoding gender and individual information in the mouse vomeronasal organ. Science 320: 535–538. DOI: 10.1126/science.1154476.

Heifetz Y , Lindner M , Garini Y and Wolfner MF (2014) Mating regulates neuromodulator ensembles at nerve termini innervating the Drosophila reproductive tract. Current Biology 24: 731–737. DOI: 10.1016/j.cub.2014.02.042.

Hickey RJ , Zhou X , Pierson JD , Ravel J and Forney LJ (2012) Understanding vaginal microbiome complexity from an ecological perspective. Translational Research 160: 267–282.

Hirsh DC (1999) The genital tract as a microbial habitat. In: Hirsh DC and Zee YC (eds) Veterinary Microbiology, pp 190–191. Wiley‐Blackwell: Oxford.

Hosken DJ and Stockley P (2004) Sexual selection and genital evolution. Trends in Ecology & Evolution 19: 87–93. DOI: 10.1016/j.tree.2003.11.012.

Hupton G , Portocarrero S , Newman M and Westneat DF (2003) Bacteria in the reproductive tracts of red‐winged blackbirds. The Condor 105: 453–464.

Jarora V , Gandotra VK , Cheema RS , Bansal AK and Dhindsa SS (2014) Relationship of in vitro cervical mucus penetration assay with IgA and IgG type antibodies in cross‐bred cows. Advances in Animal and Veterinary Sciences 2: 606–611. DOI: 10.14737/journal.aavs/2014/2.11.606.611.

Jennions MD and Petrie M (1997) Variation in mate choice and mating preferences: a review of causes and consequences. Biological Reviews 72: 283–327. DOI: 10.1111/j.1469‐185X.1997.tb00015.x.

Kalbe M , Eizaguerre C , Dankert I , et al. (2009) Lifetime reproductive success is maximized with optimal MHC diversity. Proceedings of the Royal Society of London B 276: 934–925. DOI: 10.1098/rspb.2008.1466.

Kamimura Y (2007) Twin intromittent organs of Drosophila for traumatic insemination. Biology Letters 3: 401–404. DOI: 10.1098/rsbl.2007.0192.

Klein S (2000) Hormones and mating system affect sex and species differences in immune function among vertebrates. Behavioural Processes 51: 149–166. DOI: 10.1016/S0376‐6357(00)00125‐X.

Kurtz J and Franz K (2003) Evidence for memory in invertebrate immunity. Nature 425: 37–38. DOI: 10.1038/425037a.

Lawniczak MKN , Barnes AI , Linklater JR , et al. (2007) Mating and immunity in invertebrates. Trends in Ecology & Evolution 22: 48–55. DOI: 10.1016/j.tree.2006.09.012.

Lenz TL , Hafer N , Samonte IE , Yeates SE and Milinski M (2018) Cryptic haplotype‐specific gamete selection yields offspring with optimal MHC immune genes. Evolution 72: 2478–2490. DOI: 10.1111/evo.13591.

Lihoreau M , Zimmer C and Rivault C (2008) Mutual mate choice: when it pays both sexes to avoid inbreeding. PLoS ONE 3: e3365. DOI: 10.1371/journal.pone.0003365.

Lockhart AB , Thrall PH and Antonovics J (1996) Sexually transmitted diseases in animals: ecology and evolutionary implications. Biological Reviews of the Cambridge Philosophical Society 71: 415–471.

Lombardo MP and Thorpe PA (2000) Microbes in tree swallow semen. Journal of Wildlife Diseases 36: 460–468.

Losdat S , Richner H , Blount JD and Helfenstein F (2011) Immune activation reduces sperm quality in the great tit. PLoS ONE 6: e22221. DOI: 10.1371/journal.pone.0022221.

Løvlie H , Gillingham MAF , Worley K , Pizzari T and Richardson DS (2013) Cryptic female choice favours sperm from major histocompatibility complex‐dissimilar males. Proceedings of the Royal Society of London B 280: 20131296. DOI: 10.1098/rspb.2013.1296.

Manirajan AB , Ratering S , Rusch V , et al. (2016) Bacterial microbiota associated with flower pollen is influenced by pollination type, and shows a high degree of diversity and species‐specificity. Environmental Microbiology 18: 5161–5174. DOI: 10.1111/1462‐2920.13524.

Marius‐Jestin V , Le Menec M , Thibault E , et al. (1987) Normal phallus flora of the gander. Journal of Veterinary Medicine, Series B 34: 67–78.

Matzinger P (2002) The danger model: a renewed sense of self. Science 296: 301–305. DOI: 10.1126/science.1071059.

Mayer A , Mora T , Rivoire O and Walczak AM (2016) Diversity of immune strategies explained by adaptation to pathogen statistics. Proceedings of the National Academy of Sciences of the United States of America 113: 8630–8635. DOI: 10.1073/pnas.1600663113.

McKean KA and Nunney L (2005) Bateman's principle and immunity: phenotypically plastic reproductive strategies predict changes in immunological sex differences. Evolution 59: 1510–1517. DOI: 10.1554/04‐657.

Milinski M , Griffiths S , Wegner KM , et al. (2005) Mate choice decisions of stickleback females predictably modified by MHC peptide ligands. Proceedings of the National Academy of Sciences of the United States of America 102: 4414–4418. DOI: 10.1073/pnas.0408264102.

Milinski M (2006) The major histocompatibility complex, sexual selection, and mate choice. Annual Review of Ecology, Evolutionn and Systematics 37: 159–186. DOI: 10.1146/annurev.ecolsys.37.091305.110242.

Mondragón‐Palomino M , John‐Arputharaj A , Pallmann M and Dresselhaus T (2017) Similarities between reproductive and immune pistil transcriptomes of Arabidopsis species. Plant Physiology 174: 1559–1575. DOI: 10.1104/pp.17.00390.

Morrow EH and Innocenti P (2012) Female postmating immune responses, immune system evolution and immunogenic males. Biological Reviews 87: 631–638. DOI: 10.1111/j.1469‐185X.2011.00214.x.

Nunn CL , Lindenfors P , Pursall ER and Rolff J (2008) On sexual dimorphism in immune function. Philosophical Transactions of the Royal Society B: Biological Sciences 364: 61–69. DOI: 10.1098/rstb.2008.0148.

Oku K , Price TAR and Wedell N (2019) Does mating negatively affect female immune defences in insects? Animal Biology 69: 117–136. DOI: 10.1163/15707563‐20191082.

Orr TJ and Brennan PLR (2015) Sperm storage: distinguishing selective processes and evaluating criteria. Trends in Ecology & Evolution 30: 261–272. DOI: 10.1016/j.tree.2015.03.006.

Otti O (2015) Genitalia‐associated microbes in insects. Insect Science 22: 325–339. DOI: 10.1111/1744‐7917.12183.

Pamminger T , Botías C , Goulson D and Hughes WOH (2018) A mechanistic framework to explain the immunosuppressive effects of neurotoxic pesticides on bees. Functional Ecology 32: 1921–1930. DOI: 10.1111/1365‐2435.13119.

Pizzari T , Dean R , Pacey A , Moore H and Bonsall MB (2008) The evolutionary ecology of pre‐ and post‐meiotic sperm senescence. Trends in Ecology & Evolution 23: 131–140. DOI: 10.1016/j.tree.2007.12.003.

Poiani A (2002) Sperm competition promoted by sexually transmitted pathogens and female immune defences. Ethology Ecology and Evolution 14: 327–340. DOI: 10.1080/08927014.2002.9522734.

Ravel J , Gajer P , Abdo Z , et al. (2011) Vaginal microbiome of reproductive‐age women. Proceedings of the National Academy of Sciences of the United States of America 108 (Suppl. 1): 4680–4687.

Reinhardt K and Siva‐Jothy MT (2005) An advantage for young sperm in the house cricket Acheta domesticus . The American Naturalist 165: 718–723.

Reinhardt K (2007) Evolutionary consequences of sperm cell aging. The Quarterly Review of Biology 82: 375–393. DOI: 10.1086/522811.

Reinhardt K , Naylor RA and Siva‐Jothy MT (2009) Situation exploitation: higher male mating success when female resistance is reduced by feeding. Evolution 63: 29–39. DOI: 10.1111/j.1558‐5646.2008.00502.x.

Reinhardt K , Anthes N and Lange R (2015) Copulatory wounding and traumatic insemination. Cold Spring Harbor Perspectives in Biology 7: a017582. DOI: 10.1101/cshperspect.a017582.

Risvanli A (2011) Reproductive immunology in mares. Asian Journal of Animal and Veterinary 6: 547–554. DOI: 10.3923/ajava.2011.547.554.

Rolff J (2002) Bateman's principle and immunity. Proceedings of the Royal Society of London B 269: 867–872. DOI: 10.1098/rspb.2002.1959.

Rolff J and Siva‐Jothy MT (2002) Copulation corrupts immunity: a mechanism for a cost of mating in insects. Proceedings of the National Academy of Sciences of the United States of America 99: 9916–9918. DOI: 10.1073/pnas.152271999.

Sadd BM and Schmid‐Hempel P (2006) Insect immunity shows specificity in protection upon secondary pathogen exposure. Current Biology 16: 1206–1210. DOI: 10.1016/j.cub.2006.04.047.

Sadd BM and Siva‐Jothy MT (2006) Self‐harm caused by an insect's innate immunity. Proceedings of the Royal Society of London B 273: 2571–2574. DOI: 10.1098/rspb.2006.3574.

Sakaluk SK , Campbell MTH , Clark AP , Johnson JC and Keorpes PA (2004) Hemolymph loss during nuptial feeding constrains male mating success in sagebrush crickets. Behavioral Ecology 15: 845–849. DOI: 10.1093/beheco/arh113.

Sanabria N , Goring D , Nürnberger T and Dubery I (2008) Self/nonself perception and recognition mechanisms in plants: a comparison of self‐incompatibility and innate immunity. The New Phytologist 178: 503–514. DOI: 10.1111/j.1469‐8137.2008.02403.x.

Sasu MA , Wall KL and Stephenson G (2010) Antimicrobial nectar inhibits a florally transmitted pathogen of a wild Cucurbita pepo (Cucurbitaceae). American Journal of Botany 97: 1025–1030. DOI: 10.3732/ajb.0900381.

Schwenke RA , Lazzaro BP and Wolfner MF (2016) Reproduction‐immunity trade‐offs in insects. Annual Review of Entomology 61: 239–256. DOI: 10.1146/annurev‐ento‐010715‐023924.

Schwenke RA and Lazzaro BP (2017) Juvenile hormone suppresses resistance to infection in mated female Drosophila melanogaster . Current Biology 27: 596–601. DOI: 10.1016/j.cub.2017.01.004.

Sheldon BC and Verhulst S (1996) Ecological immunology: costly parasite defences and trade‐offs in evolutionary ecology. Trends in Ecology & Evolution 11: 317–321. DOI: 10.1016/0169‐5347(96)10039‐2.

Siva‐Jothy MT (2009) Reproductive immunity. In: Rolff J and Reynolds SE (eds) Insect Infection and Immunity: Evolution, Ecology, and Mechanisms, pp 1–10. Oxford University Press: Oxford.

Siva‐Jothy MT , Zhong W , Naylor R , et al. (2019) Female bed bugs (Cimex lectularius L) anticipate the immunological consequences of traumatic insemination via feeding cues. Proceedings of the National Academy of Sciences of the United States of America 116: 14682–14687. DOI: 10.1073/pnas.1904539116.

Skau PA and Folstad I (2003) Do bacterial infections cause reduced ejaculate quality? A meta‐analysis of antibiotic treatment of male infertility. Behavioral Ecology 14: 40–47.

Suri A (2004) Sperm specific proteins‐potential candidate molecules for fertility control. Reproductive Biology and Endocrinology 2: 10. DOI: 10.1186/1477‐7827‐2‐10.

Tarín JJ , Pérez‐Albalá S and Cano A (2000) Consequences on offspring of abnormal function in ageing gametes. Human Reproduction Update 6: 532–549. DOI: 10.1093/humupd/6.6.532.

Tian L , Guo E , Diao Y , et al. (2010) Genome‐wide regulation of innate immunity by juvenile hormone and 20‐hydroxyecdysone in the Bombyx fat body. BMC Genomics 11: 549. DOI: 10.1186/1471‐2164‐11‐549.

Tremellen K (2008) Oxidative stress and male infertility – a clinical perspective. Human Reproduction Update 14: 243–258. DOI: 10.1093/humupd/dmn004.

Van Haren MM , Liljestrand Rönn J , Schilthuizen M and Arnqvist G (2017) Postmating sexual selection and the enigmatic jawed genitalia of Callosobruchus subinnotatus . Biology Open 6: 1008–1012. DOI: 10.1242/bio.025684.

Virecoulon F , Wallet F , Fruchart‐Flamenbaum A , et al. (2005) Bacterial flora of the low male genital tract in patients consulting for infertility. Andrologia 37: 160–165.

Westra ER , van Houte S , Oyesiku‐Blakemore S , et al. (2015) Parasite exposure drives selective evolution of constitutive versus inducible defense. Current Biology 25: 1043–1049. DOI: 10.1016/j.cub.2015.01.065.

White BA , Creedon DJ , Nelson KE and Wilson BA (2011) The vaginal microbiome in health and disease. Trends in Endocrinology & Metabolism 22: 389–393.

Wigby S , Suarez SS , Lazzaro BP , Pizzari T and Wolfner MF (2019) Chapter eight – Sperm success and immunity. Current Topics in Developmental Biology 135: 287–313. DOI: 10.1016/bs.ctdb.2019.04.002.

Wira CR , Rodriguez‐Garcia M and Patel MV (2015) The role of sex hormones in immune protection of the female reproductive tract. Nature Reviews Immunology 15: 217–230. DOI: 10.1038/nri3819.

Ylönen H and Haapakoski M (2016) Risk of inbreeding: problem of mate choice and fitness effects? Israel Journal of Ecology and Evolution 62: 155–161. DOI: 10.1080/15659801.2015.1073452.

Zhang X , Liu W , Nagae TT , et al. (2017) Structural basis for receptor recognition of pollen tube attraction peptides. Nature Communications 8: 1331. DOI: 10.1038/s41467‐017‐01323‐8.

Zhong W , McClure CD , Evans CR , et al. (2013) Immune anticipation of mating in Drosophila: Turandot M promotes immunity against sexually transmitted fungal infections. Proceedings of the Royal Society of London B 280: 20132018. DOI: 10.1098/rspb.2013.2018.

Zhou Y , Li M , Zhao F , et al. (2016) Floral nectary morphology and proteomic analysis of nectar of Liriodendron tulipifera Linn. Frontiers in Plant Science 7: 826. DOI: 10.3389/fpls.2016.00826.

Ziegler A , Kentenich H and Uchanska‐Ziegler B (2005) Female choice and the MHC. Trends in Immunology 26: 496–502. DOI: 10.1016/

Further Reading

Otti O , Naylor RA , Siva‐Jothy MT and Reinhardt K (2009) Bacteriolytic activity in the ejaculate of an insect. The American Naturalist 174: 292–295.

Otti O , McTighe AP and Reinhardt K (2013) In vitro antimicrobial sperm protection by an ejaculate‐like substance. Functional Ecology 27: 219–226. DOI: 10.1111/1365‐2435.12025.

Otti O , Deines P , Hammerschmidt K and Reinhardt K (2017) Regular wounding in a natural system: bacteria associated with reproductive organs of bedbugs and their quorum sensing abilities. Frontiers in Immunology 8: 1855. DOI: 10.3389/fimmu.2017.01855.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Barribeau, Seth M, and Otti, Oliver(Jul 2020) Sexual Reproduction and Immunity. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0028146]