Globozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).

Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility.

Globozoospermia is a rare condition that is estimated to affect 1 in 65,000 men. It is most common in North Africa, where it accounts for approximately 1 in 100 cases of male infertility.

Globozoospermia is most commonly caused by mutations in the DPY19L2 gene, which are found in about 70 percent of men with this condition. Mutations in other genes likely also cause globozoospermia.

The DPY19L2 gene provides instructions for making a protein that is found in developing sperm cells. The DPY19L2 protein is involved in the development of the acrosome and elongation of the sperm head, which are integral steps in sperm cell maturation. Mutations in the DPY19L2 gene result in a loss of functional DPY19L2 protein. As a result, sperm cells have no acrosome and do not elongate properly. Without an acrosome, the abnormal sperm are unable to get through the outer membrane of an egg cell to fertilize it, leading to infertility in affected men. Researchers have described other characteristics of the abnormal sperm cells that make fertilization of an egg cell difficult, although it is not clear how changes in the DPY19L2 gene are involved in development of these characteristics.

Genetic Testing Information

• Genetic Testing Registry: Globozoospermia

Genetic and Rare Diseases Information Center

• Male infertility due to globozoospermia

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• SPERMATOGENIC FAILURE 9; SPGF9

Scientific Articles on PubMed

• PubMed

• Coutton C, Zouari R, Abada F, Ben Khelifa M, Merdassi G, Triki C, Escalier D, Hesters L, Mitchell V, Levy R, Sermondade N, Boitrelle F, Vialard F, Satre V, Hennebicq S, Jouk PS, Arnoult C, Lunardi J, Ray PF. MLPA and sequence analysis of DPY19L2 reveals point mutations causing globozoospermia. Hum Reprod. 2012 Aug;27(8):2549-58. doi: 10.1093/humrep/des160. Epub 2012 May 24. Citation on PubMed
• Escoffier J, Yassine S, Lee HC, Martinez G, Delaroche J, Coutton C, Karaouzene T, Zouari R, Metzler-Guillemain C, Pernet-Gallay K, Hennebicq S, Ray PF, Fissore R, Arnoult C. Subcellular localization of phospholipase Czeta in human sperm and its absence in DPY19L2-deficient sperm are consistent with its role in oocyte activation. Mol Hum Reprod. 2015 Feb;21(2):157-68. doi: 10.1093/molehr/gau098. Epub 2014 Oct 29. Citation on PubMed or Free article on PubMed Central
• Harbuz R, Zouari R, Pierre V, Ben Khelifa M, Kharouf M, Coutton C, Merdassi G, Abada F, Escoffier J, Nikas Y, Vialard F, Koscinski I, Triki C, Sermondade N, Schweitzer T, Zhioua A, Zhioua F, Latrous H, Halouani L, Ouafi M, Makni M, Jouk PS, Sele B, Hennebicq S, Satre V, Viville S, Arnoult C, Lunardi J, Ray PF. A recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation. Am J Hum Genet. 2011 Mar 11;88(3):351-61. doi: 10.1016/j.ajhg.2011.02.007. Citation on PubMed or Free article on PubMed Central
• Koscinski I, Elinati E, Fossard C, Redin C, Muller J, Velez de la Calle J, Schmitt F, Ben Khelifa M, Ray PF, Kilani Z, Barratt CL, Viville S. DPY19L2 deletion as a major cause of globozoospermia. Am J Hum Genet. 2011 Mar 11;88(3):344-50. doi: 10.1016/j.ajhg.2011.01.018. Erratum In: Am J Hum Genet. 2011 Apr 8;88(4):517. Ray, Pierre [corrected to Ray, Pierre F]. Citation on PubMed or Free article on PubMed Central
• Ounis L, Zoghmar A, Coutton C, Rouabah L, Hachemi M, Martinez D, Martinez G, Bellil I, Khelifi D, Arnoult C, Faure 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
• Perrin A, Coat C, Nguyen MH, Talagas M, Morel F, Amice J, De Braekeleer M. Molecular cytogenetic and genetic aspects of globozoospermia: a review. Andrologia. 2013 Feb;45(1):1-9. doi: 10.1111/j.1439-0272.2012.01308.x. Epub 2012 May 10. Citation on PubMed
• Pierre V, Martinez G, Coutton C, Delaroche J, Yassine S, Novella C, Pernet-Gallay K, Hennebicq S, Ray PF, Arnoult C. Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus. Development. 2012 Aug;139(16):2955-65. doi: 10.1242/dev.077982. Epub 2012 Jul 4. Citation on PubMed
• Yassine S, Escoffier J, Martinez G, Coutton C, Karaouzene T, Zouari R, Ravanat JL, Metzler-Guillemain C, Lee HC, Fissore R, Hennebicq S, Ray PF, Arnoult C. Dpy19l2-deficient globozoospermic sperm display altered genome packaging and DNA damage that compromises the initiation of embryo development. Mol Hum Reprod. 2015 Feb;21(2):169-85. doi: 10.1093/molehr/gau099. Epub 2014 Oct 29. Citation on PubMed or Free article on PubMed Central