Wikipedia

User:Edinburghstudent/sandbox

< User:Edinburghstudent

Globozoospermia

edit

Introduction/Abstract

edit

Globozoospermia (also known as ‘round-headed sperm syndrome’[1] is a rare and severe form of monomorphic teratozoospermia. This means that the spermatozoa show the same abnormality, and over 85% of spermatozoa in sperm have this abnormality[1]. Globozoospermia is responsible for less than 0.1% of male infertility[2]. It characterised by round-headed spermatozoa with no acrosome, an abnormal nuclear membrane and midpiece defects[1]. Affected males therefore suffer from either reduced fertility or infertility[2]. Studies suggest that globozoospermia can be either total (100% round-headed spermatozoa with no acrosomes) or partial (<100% of spermatozoa affected), however it is unclear whether these two forms are variations on the same syndrome, or actually different syndromes[2].

Studies have suggested mutations or deletions in three genes are responsible for this condition: SPATA16, PICK1 and DPY19L2[1]. 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[2].

Tables and Figures

edit
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.
SPATA 16 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.

Table 1: Gene mutations that have been identified in globozoospermia and the impact these mutations have on sperm function and successful fertilization [3].

 
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[4].

Genetic contribution

A mutation in the spermatogenesis specific gene SPATA16 is responsible for globozoospermia. The gene was first identified in a family where three out of six brother were homozygous for the mutation, their sperm was acrosomeless and showed round headedness. [5]

Types of globozoospermia

Type 1= lack of acrosome and acrosomal enzymes and spherical arrangement of the chromatin.

Type 2= some acrosomal covering with a conical nucleus. Some large cytoplasmic droplets indicating secondary degenerative changes.[6]

Characteristics of globozoospermia

Globozoospermia is typically round headed sperm that lacks an acrosome and a rounded nucleus[2]. Two types of globozoospermia have been characterised. Type I is a complete lack of acrosome and acrosomal enzymes meaning the sperm is completely unable to penetrate the Zona pellucida. Type II is sperm that has some acrosomal covering surrounded by large droplets of cytoplasmic material suggesting secondary degenerative changes. Infertility in type II is thought to be due to poor mobility of the sperm resulting in slow movement and difficulty to fertilise the egg [7].

Partial globozoospermia is defined at patients that have 20-60% of round acrosomeless spermatozoa but normal sperm is also identified in the sperm count. [3]

Symptoms of globozoospermia

Aside from the affect on male fertility globozoospermia is symptomless. Males with globozoospermia have normal physical and mental development normal clinical features and normal hormonal profile [3]

Medical Treatment for Globozoospermia

The presence if round headed sperm in a semen analysis sample confirms the diagnosis of globozoospermia. The lack of acrosome (another morphological feature of globozoospermia) can be ascertained by a technique known as immunofluorescence.[8]

Until 1995, the only option for men with globozoospermia to have children was through adoption or sperm donation.[9] With the advancement of assisted reproductive techniques (ART) it is now possible for those with globozoospermia to have their own children. [10] The main technique used is intracytoplasmic sperm injection (ICSI) where fertilisation is achieved by a single sperm being injected into the egg[11] (Wong and Ledger., 2013). Some studies have shown it is possible for a viable embryo to be created with this technique alone[7], however others have found it necessary to also use calcium ionophore treatment for fertilisation to be successful.[10] 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[10].

The treatment options currently available focus on overcoming the prognosis of infertility which is associated with globozoospermia. So far there doesn’t seem to be any treatment options to prevent or cure globozoospermia.

Globozoospermia: Current Research

Research into globozoospermia is aimed at improving understanding of its cause and developing treatment options[3].

Genetics:

The observation has been made many times that globozoospermia arises in siblings which points towards an underlying genetic cause[3]. Recent progress has been made into determining what genes could be implicated in this pathology, with the following genes being identified as having a possible role: DPY19L2, PICK1, SPATA 16[1]. 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[12], Hrb[13] and Csnka2[14]. 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[1].

ICSI:

The development of intracytoplasmic sperm injection made conception a possibility for patients with a variety of male infertility conditions, including globozoospermia[15]. However, fertility rates with this approach are still low, and research is ongoing into how this can be improved[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[16]) is more likely to result in conception than ICSI alone[17]. 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)[18].

  1. ^ a b c d e f De Braekeleer, Marc; Nguyen, Minh Huong; Morel, Frédéric; Perrin, Aurore (2015-04-01). "Genetic aspects of monomorphic teratozoospermia: a review". Journal of Assisted Reproduction and Genetics. 32 (4): 615–623. doi:10.1007/s10815-015-0433-2. ISSN 1058-0468. PMC 4380889. PMID 25711835.
  2. ^ a b c d e Dam, A. H. D. M.; Feenstra, I.; Westphal, J. R.; Ramos, L.; van Golde, R. J. T.; Kremer, J. a. M. (2007-02-01). "Globozoospermia revisited". Human Reproduction Update. 13 (1): 63–75. doi:10.1093/humupd/dml047. ISSN 1355-4786. PMID 17008355.
  3. ^ a b c d e f Chansel-Debordeaux, L.; Dandieu, S.; Bechoua, S.; Jimenez, C. (2015-11-01). "Reproductive outcome in globozoospermic men: update and prospects". Andrology. 3 (6): 1022–1034. doi:10.1111/andr.12081. ISSN 2047-2927. PMID 26445006.
  4. ^ "Acrosome". Wikipedia, the free encyclopedia. 2016-09-28.
  5. ^ "Homozygous Mutation in SPATA16 Is Associated with Male Infertility in Human Globozoospermia". {{cite journal}}: Cite journal requires |journal= (help)
  6. ^ Vicari, Enzo; Perdichizzi, Anna; Palma, Adele De; Burrello, Nunziatina; D'Agata, Rosario; Calogero, Aldo E. (2002-08-01). "Globozoospermia is associated with chromatin structure abnormalities: Case report". Human Reproduction. 17 (8): 2128–2133. doi:10.1093/humrep/17.8.2128. ISSN 0268-1161. PMID 12151448.
  7. ^ a b Stone, S.; O'Mahony, F.; Khalaf, Y.; Taylor, A.; Braude, P. (2000-01-01). "A normal livebirth after intracytoplasmic sperm injection for globozoospermia without assisted oocyte activation: Case Report". Human Reproduction. 15 (1): 139–141. doi:10.1093/humrep/15.1.139. ISSN 0268-1161. PMID 10611203.
  8. ^ Koscinski, Isabelle; ElInati, Elias; Fossard, Camille; Redin, Claire; Muller, Jean; Velez de la Calle, Juan; Schmitt, Françoise; Ben Khelifa, Mariem; Ray, Pierre (2011-03-11). "DPY19L2 Deletion as a Major Cause of Globozoospermia". American Journal of Human Genetics. 88 (3): 344–350. doi:10.1016/j.ajhg.2011.01.018. ISSN 0002-9297. PMC 3059416. PMID 21397063. {{cite journal}}: no-break space character in |last6= at position 6 (help); no-break space character in |last8= at position 4 (help)
  9. ^ Taylor, SL; Yoon, SY; Morshedi, MS; Lacey, DR; Jellerette, T; Fissore, RA; Oehninger, S (2010-04-01). "Complete globozoospermia associated with PLCζ deficiency treated with calcium ionophore and ICSI results in pregnancy". Reproductive biomedicine online. 20 (4): 559–564. doi:10.1016/j.rbmo.2009.12.024. ISSN 1472-6483. PMC 2847674. PMID 20133201.
  10. ^ a b c Tejera, Alberto; Mollá, Marta; Muriel, Lourdes; Remohí, Jose; Pellicer, Antonio; De Pablo, Jose Luis (2008-10-01). "Successful pregnancy and childbirth after intracytoplasmic sperm injection with calcium ionophore oocyte activation in a globozoospermic patient". Fertility and Sterility. 90 (4): 1202.e1–5. doi:10.1016/j.fertnstert.2007.11.056. ISSN 1556-5653. PMID 18359025.
  11. ^ Wong, May Y. W.; Ledger, William L. (2013-01-01). "Is ICSI Risky?". Obstetrics and Gynecology International. 2013. doi:10.1155/2013/473289. ISSN 1687-9589. PMC 3600334. PMID 23577031.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ^ Yao, Ryoji; Ito, Chizuru; Natsume, Yasuko; Sugitani, Yoshinobu; Yamanaka, Hitomi; Kuretake, Shoji; Yanagida, Kaoru; Sato, Akira; Toshimori, Kiyotaka (2002-08-20). "Lack of acrosome formation in mice lacking a Golgi protein, GOPC". Proceedings of the National Academy of Sciences of the United States of America. 99 (17): 11211–11216. doi:10.1073/pnas.162027899. ISSN 0027-8424. PMC 123235. PMID 12149515.
  13. ^ Kang-Decker, N.; Mantchev, G. T.; Juneja, S. C.; McNiven, M. A.; van Deursen, J. M. (2001-11-16). "Lack of acrosome formation in Hrb-deficient mice". Science (New York, N.Y.). 294 (5546): 1531–1533. doi:10.1126/science.1063665. ISSN 0036-8075. PMID 11711676.
  14. ^ Xu, X.; Toselli, P. A.; Russell, L. D.; Seldin, D. C. (1999-09-01). "Globozoospermia in mice lacking the casein kinase II alpha' catalytic subunit". Nature Genetics. 23 (1): 118–121. doi:10.1038/12729. ISSN 1061-4036. PMID 10471512.
  15. ^ Neri, Queenie V.; Lee, Bora; Rosenwaks, Zev; Machaca, Khaled; Palermo, Gianpiero D. (2014-01-01). "Understanding fertilization through intracytoplasmic sperm injection (ICSI)". Cell Calcium. 55 (1): 24–37. doi:10.1016/j.ceca.2013.10.006. ISSN 1532-1991. PMC 4046257. PMID 24290744.
  16. ^ Dedkova, E. N.; Sigova, A. A.; Zinchenko, V. P. (2000-01-01). "Mechanism of action of calcium ionophores on intact cells: ionophore-resistant cells". Membrane & Cell Biology. 13 (3): 357–368. ISSN 1023-6597. PMID 10768486.
  17. ^ Karaca, Nilay; Akpak, Yasam Kemal; Oral, Serkan; Durmus, Tugce; Yilmaz, Rabiye (2015-01-01). "A Successful Healthy Childbirth in a Case of Total Globozoospermia with Oocyte Activation by Calcium Ionophore". Journal of Reproduction & Infertility. 16 (2): 116–120. ISSN 2228-5482. PMC 4386086. PMID 25927030.
  18. ^ Kamali-Dolat Abadi, Majid; Tavalaee, Marziyeh; Shahverdi, Abdolhossein; Nasr-Esfahani, Mohammad Hossein (2016-01-01). "Evaluation of PLCζ and PAWP Expression in Globozoospermic Individuals". Cell Journal (Yakhteh). 18 (3): 438–445. ISSN 2228-5806. PMC 5011332. PMID 27602326.
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Edinburghstudent/sandbox&oldid=741578949"