{{Infobox medical condition | name = | synonym = '''Round-headed sperm syndrome'''<ref name=":0">{{Cite journal|last1=De Braekeleer|first1=Marc|last2=Nguyen|first2=Minh Huong|last3=Morel|first3=Frédéric|last4=Perrin|first4=Aurore|date=2015-04-01|title=Genetic aspects of monomorphic teratozoospermia: a review|journal=Journal of Assisted Reproduction and Genetics|volume=32|issue=4|pages=615–623|doi=10.1007/s10815-015-0433-2|issn=1058-0468|pmc=4380889|pmid=25711835}}</ref> | image = Globozoospermia.png | width = | alt = | caption = Figure 1: Diagram representing the morphology of normal sperm. Areas surrounded by an orange box represent areas changed in the sperm of an individual with globozoospermia. Orange boxes highlight the specifics of the changed areas in globozoospermia. | pronounce = | field = <!-- from Wikidata, can be overwritten --> | symptoms = | onset = | duration = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | frequency = | deaths = }} '''Globozoospermia''' is a rare and severe form of monomorphic [[Teratospermia|teratozoospermia]]. This means that the [[Spermatozoon|spermatozoa]] show the same abnormality, and over 85% of spermatozoa in sperm have this abnormality.<ref name=":0" /> Globozoospermia is responsible for less than 0.1% of male infertility.<ref name=":1">{{Cite journal|last1=Dam|first1=A. H. D. M.|last2=Feenstra|first2=I.|last3=Westphal|first3=J. R.|last4=Ramos|first4=L.|last5=van Golde|first5=R. J. T.|last6=Kremer|first6=J. a. M.|date=2007-02-01|title=Globozoospermia revisited|journal=Human Reproduction Update|volume=13|issue=1|pages=63–75|doi=10.1093/humupd/dml047|issn=1355-4786|pmid=17008355|doi-access=free}}</ref> It is characterised by round-headed spermatozoa without [[acrosome]]s, an abnormal [[nuclear membrane]] and midpiece defects.<ref name=":0" /> Affected males therefore suffer from either reduced fertility or infertility.<ref name=":1" /> Studies suggest that globozoospermia can be either total (100% round-headed spermatozoa without acrosomes) or partial (20-60% round acrosomeless spermatozoa with normal sperm also identified in the sperm count),<ref name=":3" /> however it is unclear whether these two forms are variations on the same syndrome, or actually different syndromes.<ref name=":1" />
Infertility in this condition results from the sperm heads missing their [[acrosome]]. These sperm, therefore, have a characteristic round or spherically shaped head. Given the absence of the acrosome, these sperm are unable to penetrate the oocyte and are unable to achieve fertilization through conventional means; however, these sperm are able to fertilize the egg through in vitro fertilization with intracytoplasmic sperm injection, which is the treatment of choice for these patients.<ref name="pmid17460092">{{cite journal| author=Meacham RB, Chemes H, Carrell D, Goldstein M| title=Globozoospermia: is there a role for varicocele repair? | journal=J Androl | year= 2007 | volume= 28 | issue= 4 | page= 490 | pmid=17460092 | doi=10.2164/jandrol.107.002907 | doi-access=free }}</ref>
Studies have suggested mutations or deletions in three genes are responsible for this condition: SPATA16, PICK1 and DPY19L2.<ref name=":0" /> ICSI ([[intracytoplasmic sperm injection]]) has previously been used to assist reproduction in globozoospermic patients, however it has not been particularly effective in all patients, due to low fertilisation rates.<ref name=":1" />
== Types of globozoospermia == There are two types of globozoospermia:
*Type 1 globozoospermia exhibits a complete lack of acrosome and acrosomal enzymes and spherical arrangement of the [[chromatin]].<ref name=":5" /> This makes the sperm completely unable to penetrate the zona pellucida.<ref name=":2">{{Cite journal|last1=Stone|first1=S.|last2=O'Mahony|first2=F.|last3=Khalaf|first3=Y.|last4=Taylor|first4=A.|last5=Braude|first5=P.|date=2000-01-01|title=A normal livebirth after intracytoplasmic sperm injection for globozoospermia without assisted oocyte activation: Case Report|journal=Human Reproduction|language=en|volume=15|issue=1|pages=139–141|doi=10.1093/humrep/15.1.139|issn=0268-1161|pmid=10611203}}</ref> *The sperm in Type 2 globozoospermia has some acrosomal covering surrounded by large droplets of cytoplasmic material, suggesting secondary degenerative changes. There is also a conical nucleus.<ref name=":5">{{Cite journal|last1=Vicari|first1=Enzo|last2=Perdichizzi|first2=Anna|last3=Palma|first3=Adele De|last4=Burrello|first4=Nunziatina|last5=D'Agata|first5=Rosario|last6=Calogero|first6=Aldo E.|date=2002-08-01|title=Globozoospermia is associated with chromatin structure abnormalities: Case report|journal=Human Reproduction|language=en|volume=17|issue=8|pages=2128–2133|doi=10.1093/humrep/17.8.2128|issn=0268-1161|pmid=12151448|doi-access=free}}</ref> It is thought that infertility in this type of globozoospermia is due to incorrect chromatin packaging which prevents proper fertilization.
== Symptoms == Aside from the effect on fertility globozoospermia is symptomless. People with globozoospermia have normal physical and mental development, normal clinical features and normal hormonal profile.<ref name=":3" />
== Genetics == {| class="wikitable" ! Genes mutated in globozoospermia ! Gene product and its normal function ! Mutation's effect on sperm in globozoospermia |- |'''[[DPY19L2]]''' – most frequent mutation in globozoospermia |Transmembrane protein localised on the acrosome of spermatids. It contributes to normal acrosome formation by anchoring the acrosome to the spermatozoa nucleus. |Sperm head elongation and acrosome formation fails causing a round-headed sperm to form so sperm are unable to bind the [[zona pellucida]] and fertilise the oocyte. Sperm concentration in the semen also reduces. |- |'''[[PICK1]]''' |Cytosolic protein found in the proacrosomal vesicles of round spermatids. It functions during protein trafficking. |Proacrosomal vesicles fail to merge causing a round-headed sperm to form so sperm are unable to bind the zona pellucida and fertilise the oocyte. |- |'''[[SPATA16]]''' |A protein:protein interaction domain located in proacrosomal vesicles and golgi apparatus. It plays a role in spermatogenesis and acrosome formation. |Acrosome is absent creating round-headed sperm unable to bind the zona pellucida and fertilise the oocyte. The gene was first identified in a family with three out of six brothers being homozygous for the mutation; their sperm was acrosomeless and showed round headedness.<ref>{{Cite journal|title=Homozygous Mutation in SPATA16 Is Associated with Male Infertility in Human Globozoospermia|journal=The American Journal of Human Genetics|volume=81|issue=4|pages=813–820|doi=10.1086/521314|pmid=17847006|pmc=2227931|date=October 2007|last1=Dam|first1=Anika H.D.M.|last2=Koscinski|first2=Isabelle|last3=Kremer|first3=Jan A.M.|last4=Moutou|first4=Céline|last5=Jaeger|first5=Anne-Sophie|last6=Oudakker|first6=Astrid R.|last7=Tournaye|first7=Herman|last8=Charlet|first8=Nicolas|last9=Lagier-Tourenne|first9=Clotilde|last10=Van Bokhoven|first10=Hans|last11=Viville|first11=Stéphane}}</ref> |} '''''Table 1:''''' [[Gene]] mutations that have been identified in globozoospermia and the impact these mutations have on sperm function and successful fertilization.<ref name=":3">{{Cite journal|last1=Chansel-Debordeaux|first1=L.|last2=Dandieu|first2=S.|last3=Bechoua|first3=S.|last4=Jimenez|first4=C.|date=2015-11-01|title=Reproductive outcome in globozoospermic men: update and prospects|journal=Andrology|volume=3|issue=6|pages=1022–1034|doi=10.1111/andr.12081|issn=2047-2927|pmid=26445006|doi-access=free}}</ref>
== Diagnosis== The presence of round headed sperm in a [[semen analysis]] sample confirms the diagnosis of globozoospermia. The lack of acrosome can be ascertained by either morphology staining or [[immunofluorescence]].<ref>{{Cite journal|last1=Koscinski|first1=Isabelle|last2=ElInati|first2=Elias|last3=Fossard|first3=Camille|last4=Redin|first4=Claire|last5=Muller|first5=Jean|last6=Velez de la Calle|first6=Juan|last7=Schmitt|first7=Françoise|last8=Ben Khelifa|first8=Mariem|last9=Ray|first9=Pierre|date=2011-03-11|title=DPY19L2 Deletion as a Major Cause of Globozoospermia|journal=American Journal of Human Genetics|volume=88|issue=3|pages=344–350|doi=10.1016/j.ajhg.2011.01.018|issn=0002-9297|pmc=3059416|pmid=21397063}}</ref>
==Treatment== Until 1995, the only options for people with globozoospermia who wished to conceive were adoption or sperm donation.<ref>{{Cite journal|last1=Taylor|first1=SL|last2=Yoon|first2=SY|last3=Morshedi|first3=MS|last4=Lacey|first4=DR|last5=Jellerette|first5=T|last6=Fissore|first6=RA|last7=Oehninger|first7=S|date=2010-04-01|title=Complete globozoospermia associated with PLCζ deficiency treated with calcium ionophore and ICSI results in pregnancy|journal=Reproductive Biomedicine Online|volume=20|issue=4|pages=559–564|doi=10.1016/j.rbmo.2009.12.024|issn=1472-6483|pmc=2847674|pmid=20133201}}</ref> With the advancement of [[Assisted reproductive technology|assisted reproductive techniques]] (ART) it is now possible for those with globozoospermia to conceive using their own sperm.<ref name=":4">{{Cite journal|last1=Tejera|first1=Alberto|last2=Mollá|first2=Marta|last3=Muriel|first3=Lourdes|last4=Remohí|first4=Jose|last5=Pellicer|first5=Antonio|last6=De Pablo|first6=Jose Luis|date=2008-10-01|title=Successful pregnancy and childbirth after intracytoplasmic sperm injection with calcium ionophore oocyte activation in a globozoospermic patient|journal=Fertility and Sterility|volume=90|issue=4|pages=1202.e1–5|doi=10.1016/j.fertnstert.2007.11.056|issn=1556-5653|pmid=18359025|doi-access=free}}</ref> The main technique used is [[intracytoplasmic sperm injection]] (ICSI) where fertilisation is achieved by a single sperm being injected into the egg.<ref>{{Cite journal|last1=Wong|first1=May Y. W.|last2=Ledger|first2=William L.|date=2013-01-01|title=Is ICSI Risky?|journal=Obstetrics and Gynecology International|volume=2013|article-number=473289|doi=10.1155/2013/473289|issn=1687-9589|pmc=3600334|pmid=23577031|doi-access=free}}</ref> Some studies have shown it is possible for a viable embryo to be created with this technique alone,<ref name=":2" /> however others have found it necessary to also use calcium [[ionophore]] treatment for fertilisation to be successful.<ref name=":4" /> Calcium ionophore treatment is used to artificially activate the oocyte. This treatment may be necessary as globozoospermic sperm can be less likely to activate the oocyte, an important stage in fertilisation.<ref name=":4" />
The treatment options currently available focus on overcoming the prognosis of infertility which is associated with globozoospermia. So far there are no treatment options to prevent or cure globozoospermia.
== Research == Research into globozoospermia is aimed at improving understanding of its cause and developing treatment options.<ref name=":3" />
=== Genetics === The observation has been made many times that globozoospermia arises in siblings which points towards an underlying genetic cause.<ref name=":3" /> Recent progress has been made into determining what genes could be implicated in this pathology, with the previously mentioned genes being found to play a role.<ref name=":0" /> There are more genes which have been shown to be mutated in globozoospermia in mice, but these are yet to be connected to the human disease process. Examples of these include Gopc,<ref>{{Cite journal|last1=Yao|first1=Ryoji|last2=Ito|first2=Chizuru|last3=Natsume|first3=Yasuko|last4=Sugitani|first4=Yoshinobu|last5=Yamanaka|first5=Hitomi|last6=Kuretake|first6=Shoji|last7=Yanagida|first7=Kaoru|last8=Sato|first8=Akira|last9=Toshimori|first9=Kiyotaka|date=2002-08-20|title=Lack of acrosome formation in mice lacking a Golgi protein, GOPC|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=99|issue=17|pages=11211–11216|doi=10.1073/pnas.162027899|issn=0027-8424|pmc=123235|pmid=12149515|bibcode=2002PNAS...9911211Y|doi-access=free}}</ref> Hrb and Csnka2.<ref>{{Cite journal|last1=Kang-Decker|first1=N.|last2=Mantchev|first2=G. T.|last3=Juneja|first3=S. C.|last4=McNiven|first4=M. A.|last5=van Deursen|first5=J. M.|date=2001-11-16|title=Lack of acrosome formation in Hrb-deficient mice|journal=Science|volume=294|issue=5546|pages=1531–1533|doi=10.1126/science.1063665|issn=0036-8075|pmid=11711676|bibcode=2001Sci...294.1531K|s2cid=10442096}}</ref><ref>{{Cite journal|last1=Xu|first1=X.|last2=Toselli|first2=P. A.|last3=Russell|first3=L. D.|last4=Seldin|first4=D. C.|date=1999-09-01|title=Globozoospermia in mice lacking the casein kinase II alpha' catalytic subunit|journal=Nature Genetics|volume=23|issue=1|pages=118–121|doi=10.1038/12729|issn=1061-4036|pmid=10471512|s2cid=21363944}}</ref> There are thousands of genes which guide the process of spermatogenesis, and knowing how they're involved in globozoospermia is an important current area of research.<ref name=":0" />
=== ICSI === The development of intracytoplasmic sperm injection made conception a possibility for patients with a variety of male infertility conditions, including globozoospermia.<ref>{{Cite journal|last1=Neri|first1=Queenie V.|last2=Lee|first2=Bora|last3=Rosenwaks|first3=Zev|last4=Machaca|first4=Khaled|last5=Palermo|first5=Gianpiero D.|date=2014-01-01|title=Understanding fertilization through intracytoplasmic sperm injection (ICSI)|journal=Cell Calcium|volume=55|issue=1|pages=24–37|doi=10.1016/j.ceca.2013.10.006|issn=1532-1991|pmc=4046257|pmid=24290744}}</ref> However, fertility rates with this approach are still low, and research is ongoing into how this can be improved.<ref name=":3" />
It has been found that treating globozoospermia with ICSI along with oocyte activation by calcium ionophore (an ion carrier used to increase intracellular calcium<ref>{{Cite journal|last1=Dedkova|first1=E. N.|last2=Sigova|first2=A. A.|last3=Zinchenko|first3=V. P.|date=2000-01-01|title=Mechanism of action of calcium ionophores on intact cells: ionophore-resistant cells|journal=Membrane & Cell Biology|volume=13|issue=3|pages=357–368|issn=1023-6597|pmid=10768486}}</ref> is more likely to result in conception than ICSI alone.<ref>{{Cite journal|last1=Karaca|first1=Nilay|last2=Akpak|first2=Yasam Kemal|last3=Oral|first3=Serkan|last4=Durmus|first4=Tugce|last5=Yilmaz|first5=Rabiye|date=2015-01-01|title=A Successful Healthy Childbirth in a Case of Total Globozoospermia with Oocyte Activation by Calcium Ionophore|journal=Journal of Reproduction & Infertility|volume=16|issue=2|pages=116–120|issn=2228-5482|pmc=4386086|pmid=25927030}}</ref> Another promising treatment area also looks at causing oocyte activation in conjunction with ICSI, this time using spermatic binding-proteins, phospholipase C zeta (PLCζ) and postacrosomal sheath WW domain binding protein (PAWP).<ref>{{Cite journal|last1=Kamali-Dolat Abadi|first1=Majid|last2=Tavalaee|first2=Marziyeh|last3=Shahverdi|first3=Abdolhossein|last4=Nasr-Esfahani|first4=Mohammad Hossein|date=2016-01-01|title=Evaluation of PLCζ and PAWP Expression in Globozoospermic Individuals|journal=Cell Journal |volume=18|issue=3|pages=438–445|issn=2228-5806|pmc=5011332|pmid=27602326}}</ref>
== References ==
{{reflist|2}}
[[Category:Testicular infertility factors]]