Macrozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).
In affected males, almost all sperm cells have abnormally large and misshapen heads. The head of the sperm cell contains the male's genetic information that is to be passed on to the next generation. Normally, the head of a sperm cell contains one copy of each chromosome. In men with macrozoospermia, the sperm cell head contains extra chromosomes, usually four copies of each instead of the usual one. This additional genetic material accounts for the larger head size of the sperm cell. Additionally, instead of having one tail (flagellum) per sperm cell, affected sperm have multiple flagella, most often four.
Because of the additional genetic material, if one of these abnormal sperm cells combines with an egg cell, the embryo will not develop or the pregnancy will result in miscarriage.
Macrozoospermia is estimated to affect 1 in 10,000 males in North Africa. The prevalence of the condition outside this region is unknown.
Mutations in the AURKC gene cause macrozoospermia. The AURKC gene provides instructions for making a protein called aurora kinase C. This protein is abundant in male testes, which are the male reproductive organs in which sperm are produced and stored. In the testes, this protein regulates the division of sperm cells. Aurora kinase C ensures that the mechanisms for cell division are in place and helps chromosomes properly align with each other so that every new sperm cell contains one copy of each chromosome after cell division.
AURKC gene mutations that cause macrozoospermia lead to the production of a nonfunctional protein or a protein that is quickly broken down. This lack of aurora kinase C blocks cell division in sperm cells. Without cell division, the chromosomes are not split among multiple new sperm cells. As a result, affected sperm cells contain extra chromosomes, usually four copies of each instead of the usual one.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- infertility associated with multi-tailed spermatozoa and excessive DNA
- large-headed multiflagellar polyploid spermatozoa
- spermatogenic failure 5
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Ben Khelifa M, Coutton C, Blum MG, Abada F, Harbuz R, Zouari R, Guichet A, May-Panloup P, Mitchell V, Rollet J, Triki C, Merdassi G, Vialard F, Koscinski I, Viville S, Keskes L, Soulie JP, Rives N, Dorphin B, Lestrade F, Hesters L, Poirot C, Benzacken B, Jouk PS, Satre V, Hennebicq S, Arnoult C, Lunardi J, Ray PF. Identification of a new recurrent aurora kinase C mutation in both European and African men with macrozoospermia. Hum Reprod. 2012 Nov;27(11):3337-46. doi: 10.1093/humrep/des296. Epub 2012 Aug 11. Citation on PubMed
- Ben Khelifa M, Zouari R, Harbuz R, Halouani L, Arnoult C, Lunardi J, Ray PF. A new AURKC mutation causing macrozoospermia: implications for human spermatogenesis and clinical diagnosis. Mol Hum Reprod. 2011 Dec;17(12):762-8. doi: 10.1093/molehr/gar050. Epub 2011 Jul 6. Citation on PubMed or Free article on PubMed Central
- Dieterich K, Soto Rifo R, Faure AK, Hennebicq S, Ben Amar B, Zahi M, Perrin J, Martinez D, Sèle B, Jouk PS, Ohlmann T, Rousseaux S, Lunardi J, Ray PF. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet. 2007 May;39(5):661-5. Epub 2007 Apr 15. Citation on PubMed
- Dieterich K, Zouari R, Harbuz R, Vialard F, Martinez D, Bellayou H, Prisant N, Zoghmar A, Guichaoua MR, Koscinski I, Kharouf M, Noruzinia M, Nadifi S, Sefiani A, Lornage J, Zahi M, Viville S, Sèle B, Jouk PS, Jacob MC, Escalier D, Nikas Y, Hennebicq S, Lunardi J, Ray PF. The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population. Hum Mol Genet. 2009 Apr 1;18(7):1301-9. doi: 10.1093/hmg/ddp029. Epub 2009 Jan 15. Citation on PubMed
- Eloualid A, Rouba H, Rhaissi H, Barakat A, Louanjli N, Bashamboo A, McElreavey K. Prevalence of the Aurora kinase C c.144delC mutation in infertile Moroccan men. Fertil Steril. 2014 Apr;101(4):1086-90. doi: 10.1016/j.fertnstert.2013.12.040. Epub 2014 Jan 30. Citation on PubMed
- Ounis L, Zoghmar A, Coutton C, Rouabah L, Hachemi M, Martinez D, Martinez G, Bellil I, Khelifi D, Arnoult C, Fauré J, Benbouhedja S, Rouabah A, Ray PF. Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men. Asian J Androl. 2015 Jan-Feb;17(1):68-73. doi: 10.4103/1008-682X.136441. Citation on PubMed or Free article on PubMed Central