Globozoospermia

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Globozoospermia
Other namesRound-headed sperm syndrome [1]
Globozoospermia.png
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.

Globozoospermia 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 is characterised by round-headed spermatozoa without acrosomes, 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 without acrosomes) or partial (20-60% round acrosomeless spermatozoa with normal sperm also identified in the sperm count), [3] however it is unclear whether these two forms are variations on the same syndrome, or actually different syndromes. [2]

Contents

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. [4]

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]

Types of globozoospermia

There are two types of globozoospermia:

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. [3]

Genetics

Genes mutated in globozoospermiaGene product and its normal functionMutation's effect on sperm in globozoospermia
DPY19L2 – most frequent mutation in globozoospermiaTransmembrane 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. [7]

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

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. [8]

Treatment

Until 1995, the only options for people with globozoospermia who wished to conceive were adoption or sperm donation. [9] With the advancement of assisted reproductive techniques (ART) it is now possible for those with globozoospermia to conceive using their own sperm. [10] The main technique used is intracytoplasmic sperm injection (ICSI) where fertilisation is achieved by a single sperm being injected into the egg. [11] Some studies have shown it is possible for a viable embryo to be created with this technique alone, [6] 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 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. [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 previously mentioned genes being found to play a role. [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 and Csnka2. [13] [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]

Related Research Articles

<span class="mw-page-title-main">Spermatozoon</span> Motile sperm cell

A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote.

<span class="mw-page-title-main">Fertilisation</span> Union of gametes of opposite sexes during the process of sexual reproduction to form a zygote

Fertilisation or fertilization, also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a zygote and initiate its development into a new individual organism or offspring. While processes such as insemination or pollination, which happen before the fusion of gametes, are also sometimes informally referred to as fertilisation, these are technically separate processes. The cycle of fertilisation and development of new individuals is called sexual reproduction. During double fertilisation in angiosperms, the haploid male gamete combines with two haploid polar nuclei to form a triploid primary endosperm nucleus by the process of vegetative fertilisation.

<span class="mw-page-title-main">Intracytoplasmic sperm injection</span> In vitro fertilization procedure

Intracytoplasmic sperm injection is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg. This technique is used in order to prepare the gametes for the obtention of embryos that may be transferred to a maternal uterus. With this method, the acrosome reaction is skipped.

<span class="mw-page-title-main">Acrosome</span> Organelle of sperm cells

The acrosome is an organelle that develops over the anterior (front) half of the head in the spermatozoa of humans, and many other animals. It is a cap-like structure derived from the Golgi apparatus. In placental mammals, the acrosome contains degradative enzymes. These enzymes break down the outer membrane of the ovum, called the zona pellucida, allowing the haploid nucleus in the sperm cell to join with the haploid nucleus in the ovum. This shedding of the acrosome, or acrosome reaction, can be stimulated in vitro by substances a sperm cell may encounter naturally such as progesterone or follicular fluid, as well as the more commonly used calcium ionophore A23187. This can be done to serve as a positive control when assessing the acrosome reaction of a sperm sample by flow cytometry or fluorescence microscopy. This is usually done after staining with a fluoresceinated lectin such as FITC-PNA, FITC-PSA, FITC-ConA, or fluoresceinated antibody such as FITC-CD46.

<span class="mw-page-title-main">Acrosome reaction</span> Sperm-meets-egg process

For fertilization to happen between a sperm and egg cell, a sperm must first fuse with the plasma membrane and then penetrate the female egg cell to fertilize it. While the fusion of the sperm cell with the egg cell's plasma membrane is relatively straightforward, penetrating the egg's protective layers, such as the zona pellucida, presents a significant challenge. Therefore, sperm cells go through a process known as the acrosome reaction, which is the reaction that occurs in the acrosome of the sperm as it approaches the egg.

Hyperactivation is a type of sperm motility. Hyperactivated sperm motility is characterised by a high amplitude, asymmetrical beating pattern of the sperm tail (flagellum). This type of motility may aid in sperm penetration of the zona pellucida, which encloses the ovum.

<span class="mw-page-title-main">A23187</span> Chemical compound

A23187 is a mobile ion-carrier that forms stable complexes with divalent cations. A23187 is also known as Calcimycin, Calcium Ionophore, Antibiotic A23187 and Calcium Ionophore A23187. It is produced at fermentation of Streptomyceschartreusensis.

Azoospermia factor (AZF) is one of several proteins or their genes, which are coded from the AZF region on the human male Y chromosome. Deletions in this region are associated with inability to produce sperm. Subregions within the AZF region are AZFa, AZFb and AZFc. AZF microdeletions are one of the major causes of male infertility for azoospermia and severe oligozoospermia males. AZF is the term used by the HUGO Gene Nomenclature Committee.

The cation channels of sperm also known as Catsper channels or CatSper, are ion channels that are related to the two-pore channels and distantly related to TRP channels. The four members of this family form voltage-gated Ca2+ channels that seem to be specific to sperm. As sperm encounter the more alkaline environment of the female reproductive tract, CatSper channels become activated by the altered ion concentration. These channels are required for proper fertilization. The study of these channels has been slow because they do not traffic to the cell membrane in many heterologous systems.

<span class="mw-page-title-main">In vitro maturation</span> Artificial maturation of harvested immature egg cells

In vitro maturation (IVM) is the technique of letting the contents of ovarian follicles and the oocytes inside mature in vitro. It can be offered to women with infertility problems, combined with In Vitro Fertilization (IVF), offering women pregnancy without ovarian stimulation.

The Genetics & IVF Institute (GIVF) is an international provider of infertility and genetics services and products, and also engages in biomedical research in these fields. The Institute was founded in 1984 by Dr. Joseph D. Schulman and associates. GIVF headquarters are in Fairfax, VA, US, and its facilities include locations in Pennsylvania, Minnesota, California, and Texas in the United States, as well as in China, Mexico, and several other countries.

Teratospermia or teratozoospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males.

Oocyteactivation is a series of processes that occur in the oocyte during fertilization.

Jacques Cohen is a Dutch embryologist based in New York, U.S. He is currently a Director at Reprogenetics LLC, Laboratory Director at ART Institute of Washington at Walter Reed National Military Medical Center, and Scientific Director of R & D at IVF-online.

The history of in vitro fertilisation (IVF) goes back more than half a century. In 1959 the first birth in a nonhuman mammal resulting from IVF occurred, and in 1978 the world's first baby conceived by IVF was born. As medicine advanced, IVF was transformed from natural research to a stimulated clinical treatment. There have been many refinements in the IVF process, and today millions of births have occurred with the help of IVF all over the world.

Antisperm antibodies (ASA) are antibodies produced against sperm antigens.

<span class="mw-page-title-main">Intracytoplasmic morphologically selected sperm injection</span>

The intracytoplasmic morphologically selected sperm injection (IMSI) is a laboratory technique used for In vitro fertilisation treatments. High-quality sperms are injected into the egg for fertilization, it is an advanced version of ICSI.

Spermatogenesis-associated protein 16 is a mammalian protein encoded by the SPATA16 gene. SPATA16, also known as NYD-SP12, is a developmental protein that aids in differentiation of germ cells for spermatogenesis and participates in acrosome formation for appropriate sperm-egg fusion. SPATA16 is located on chromosome 3 at position 26.31 and is a member of the tetratricopeptide repeat-like superfamily, which facilitate interactions and assemblies between proteins and protein complexes.

Sarah Martins da SilvaFRCOG is a British gynaecologist and researcher specialising in male infertility. Martins da Silva is a Clinical Reader in reproductive medicine at the University of Dundee. She also works as an honorary consultant gynaecologist at Ninewells Hospital in Dundee, specialising in fertility problems and assisted conception. She was named one of the BBC's "100 Women of 2019" for her contribution to fertility science.

Dmitri Dozortsev is a Russian-American physician scientist, inventor and researcher. Dozortsev's contributions in research and publications are mostly in the areas of human reproductive medicine and biology. In particular, he is best known for his studies of in vitro fertilisation and embryo transfer. Dozortsev currently serves as President of the American College of Embryology and as Director of Omni-Med laboratories.

References

  1. 1 2 3 4 5 6 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. 1 2 3 4 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. 1 2 3 4 5 6 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. ↑ Meacham RB, Chemes H, Carrell D, Goldstein M (2007). "Globozoospermia: is there a role for varicocele repair?". J Androl. 28 (4): 490. doi: 10.2164/jandrol.107.002907 . PMID   17460092.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. 1 2 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.
  6. 1 2 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.
  7. ↑ Dam, Anika H.D.M.; Koscinski, Isabelle; Kremer, Jan A.M.; Moutou, Céline; Jaeger, Anne-Sophie; Oudakker, Astrid R.; Tournaye, Herman; Charlet, Nicolas; Lagier-Tourenne, Clotilde; Van Bokhoven, Hans; Viville, Stéphane (October 2007). "Homozygous Mutation in SPATA16 Is Associated with Male Infertility in Human Globozoospermia". The American Journal of Human Genetics. 81 (4): 813–820. doi:10.1086/521314. PMC   2227931 . PMID   17847006.
  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.
  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. 1 2 3 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: 473289. doi: 10.1155/2013/473289 . ISSN   1687-9589. PMC   3600334 . PMID   23577031.
  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. Bibcode:2002PNAS...9911211Y. 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. 294 (5546): 1531–1533. Bibcode:2001Sci...294.1531K. doi:10.1126/science.1063665. ISSN   0036-8075. PMID   11711676. S2CID   10442096.
  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. S2CID   21363944.
  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. 18 (3): 438–445. ISSN   2228-5806. PMC   5011332 . PMID   27602326.
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