Editing Spermatocyte

{{short description|Sperm precursor cell that undergoes meiosis}}
[[File:Figure 28 01 04.jpg|right|thumb|500px|[[Spermatogenesis]] as the cells progress from [[spermatogonia|spermatogium]], to primary spermatocytes, to secondary spermatocytes, to [[spermatids]] and to [[sperm]].]]

'''Spermatocytes''' are a type of [[male]] [[gametocyte]] in animals. They derive from immature [[germ cells]] called [[spermatogonia]]. They are found in the [[testis]], in a structure known as the [[seminiferous tubules]].<ref name="Med phy">{{cite book |last1=Boron |first1=Walter |first2=Emile L. |last2=Boulpaep |title=Medical physiology a cellular and molecular approach |location=Philadelphia |publisher=Saunders Elsevier |year=2012 |type=Print |isbn=978-1-4377-1753-2 |chapter=54 |edition=Updated second|url=https://archive.org/details/medicalphysiolog0000unse_a0b3/|pages=1129, 1133-1134, 1137-1138}}<!--p1129--></ref> There are two types of spermatocytes, primary and secondary spermatocytes. Primary and secondary spermatocytes are formed through the process of [[spermatocytogenesis]].<ref name=sperm />

Primary spermatocytes are [[diploid]] (2N) cells. After [[meiosis I]], two secondary spermatocytes are formed. Secondary spermatocytes are [[haploid]] (N) cells that contain half the number of chromosomes.<ref name="Med phy" /><!--p1137-1138-->

In all animals, [[Male|males]] produce spermatocytes, even [[hermaphrodites]] such as [[Caenorhabditis elegans|''C. elegans'']], which exist as a male or hermaphrodite. In hermaphrodite ''C. elegans'', sperm production occurs first and is then stored in the [[spermatheca]]. Once the [[egg cell|eggs]] are formed, they are able to self-fertilize and produce up to 350 [[offspring|progeny]].<ref>{{cite book|editor-last1=Riddle |editor-first1=DL | editor-last2=Blumenthal |editor-first2=T |editor-last3=Meyer  |editor-first3=B.J.|display-editors = 3 |editor-last4=Priess|editor-first4=J.R. |title=C. elegans II |edition=2nd |location=Cold Spring Harbor. NY |publisher=[[Cold Spring Harbor Laboratory Press]] |year=1997 |section=I, The Biological Model |url=https://www.ncbi.nlm.nih.gov/books/NBK20086/ |access-date=April 13, 2014}}</ref>

==Development==
[[File:Mitosis (263 06) Grasshopper testes (Spermatogonia).jpg|thumb|[[Spermatogonia]] going through [[mitosis]] to form primary spermatocytes in Grasshopper [[testes]].|alt=|left]][[File:Spermatocytogenesis.png|thumb|200px|[[Spermatocytogenesis]]|alt=]]At [[puberty]], [[spermatogonia]] located along the walls of the [[seminiferous tubules]] within the [[testis]] will be initiated and start to divide [[mitotically]], forming two types of A cells that contain an oval shaped nucleus with a nucleolus attached to the nuclear envelope; one is dark (Ad) and the other is pale (Ap). The Ad cells are spermatogonia that will stay in the basal compartment (outer region of the tubule); these cells are reserve [[Spermatogonial Stem Cells|spermatogonial stem cells]] that do not usually undergo mitosis. Type Ap are actively-dividing [[Spermatogonial Stem Cells|spermatogonial stem cells]] which begin differentiation to type B spermatogonia, which have round nuclei and heterochromatin attached to the nuclear envelope and the center of nucleolus.<ref>{{Cite journal|last1=Boitani|first1=Carla|last2=Di Persio|first2=Sara|last3=Esposito|first3=Valentina|last4=Vicini|first4=Elena|date=2016-03-05|title=Spermatogonial cells: mouse, monkey and man comparison|journal=Seminars in Cell & Developmental Biology|doi=10.1016/j.semcdb.2016.03.002|issn=1096-3634|pmid=26957475|volume=59|pages=79–88}}</ref> Type B cells will move on to the adluminal compartment (towards the inner region of tubule) and become primary spermatocytes; this process takes about 16 days to complete.<ref name="sperm">{{cite web|last1=Schöni-Affolter|first1=Franzisk|last2=Dubuis-Grieder|first2=Christine|last3=Strauch|first3=Erik Strauch|title=Spermatogenesis|url=http://www.embryology.ch/anglais/cgametogen/spermato03.html#entwicklung|access-date=22 March 2014}}</ref><ref name="Type A and B (JA)">{{cite journal|first=Y|last=Clermont|title=Renewal of spermatogonia in man|year=1966|volume=118|issue=2|journal=American Journal of Anatomy|pages=509–524|doi=10.1002/aja.1001180211|pmid=5917196}}</ref>

The primary spermatocytes within the adluminal compartment will continue on to [[meiosis I]] and divide into two daughters cells, known as secondary spermatocytes, a process which takes 24 days to complete. Each secondary spermatocyte will form two [[spermatids]] after [[meiosis II]].<ref name="Med phy" /><!--p1137-->

Although spermatocytes that divide mitotically and meiotically are sensitive to [[radiation]] and [[cancer]], [[spermatogonial stem cells]] are not. Therefore, after termination of [[radiation therapy]] or [[chemotherapy]], the spermatognia stems cells may re-initiate the formation of spermatogenesis.<ref name="type a and b">{{cite book|url=https://www.inkling.com/read/histology-cell-biology-kierszenbaum-tres-3rd/chapter-20/the-testes|title=Histology and cell biology : an introduction to pathology|last=Tres|first=Abraham L.|last2=Kierszenbaum|first2=Laura L.|publisher=Saunders|year=2012|isbn=9780323078429|edition=3rd|location=Philadelphia, PA|pages=Chapter 20}}</ref>

[[File:1810 Major Pituitary Hormones.jpg|thumb|Hormones produced by the Pituitary gland. GnRH is secreted by the hypothalamus, which induces anterior pituitary to produce FSH and LH upon puberty.]]

===Role of hormones===
The formation of primary spermatocytes (a process known as [[spermatocytogenesis]]) begins in humans when a male is sexually matured at [[puberty]], around the age of 10 through 14.<ref name=gbook>{{cite book|last=Starr|first=Cecie|last2=Taggart|first2=Ralph|last3=Evers|first3=Christine|last4=Starr|first4=Lisa|title=Animal Structure & Function|date=January 1, 2012|publisher=Cengage Learning|isbn=9781133714071|pages=736}}</ref> Formation is initiated upon the pulsated surges of [[gonadotropin-releasing hormone]] (GnRH) from the [[hypothalamus]], which leads to the secretion of [[follicle-stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH) produced by the [[anterior pituitary gland]]. The release of FSH into the testes will enhance spermatogenesis and lead to the development of [[Sertoli cells]], which act as nursing cells where [[spermatids]] will go to mature after [[meiosis II]]. LH promotes [[Leydig cell]] secretion of [[testosterone]] into the testes and blood, which induce spermatogenesis and aid the formation of secondary sex characteristics. From this point on, the secretion of FSH and LH (inducing production of testosterone) will stimulate [[spermatogenesis]] until the male dies.<ref name="human Phys book">{{cite book|last=Sherwood|first=Lauralee|title=Human physiology : from cells to systems|year=2010|publisher=Brooks/Cole, Cengage Learning|location=Australia|isbn=978-0495391845|page=751|edition=7th}}</ref> Increasing the [[hormones]] FSH and LH in males will not increase the rate of spermatogenesis. However, with age, the rate of production will decrease, even when the amount of hormone that is secreted is constant; this is due to higher rates of degeneration of [[germ cells]] during [[meiotic]] [[prophase]].<ref name="Med phy" /><!--p1133-1134-->

===Cell type summary===
In the following table, ploidy, copy number and chromosome/chromatid counts listed are for a single cell, generally prior to DNA synthesis and division (in G<sub>1</sub> if applicable). Primary spermatocytes are arrested after DNA synthesis and prior to division.<ref name="Med phy" /><!--p1137-1138--><ref name=sperm /> 
{| class="wikitable"
|-
!Cell !! Type !! Ploidy/[[Chromosomes]] in human  !!  DNA copy number/[[Chromatids]] in human  !!  Process entered by cell  !!  Duration
 |- 
 |[[spermatogonium]] (types Ad, Ap and B) ||[[germ cells]]|| diploid (2N) / 46 || 2C / 46 || [[spermatocytogenesis]] ([[mitosis]]) || 16 days
 |- 
 | primary spermatocyte ||male [[gametocyte]]|| diploid (2N) / 46 || 4C / 2x46 || [[spermatocytogenesis]] ([[meiosis I]]) || 24 days
 |- 
 | secondary spermatocyte ||male gametocyte|| haploid (N) / 23 || 2C / 46 || [[spermatidogenesis]] ([[meiosis II]]) || A few hours
 |- 
 | [[spermatid]]s ||male [[gametid]]|| haploid (N) / 23  || 1C / 23 || [[spermiogenesis]] ||24 days
 |- 
 |[[spermatozoid]]s ||[[sperm]]|| haploid (N) / 23 || 1C / 23 || spermiation || 64 days (total)
|}

==Physiology==
===Damage, repair, and failure===
Spermatocytes regularly overcome double-strand breaks and other [[DNA damage (naturally occurring)|DNA damages]] in the prophase stage of [[meiosis]]. These damages can arise by the programmed activity of [[Spo11]], an enzyme employed in meiotic recombination, as well as by un-programmed breakages in DNA, such as those caused by [[oxidative stress|oxidative free radicals]] produced as products of normal metabolism. These damages are repaired by homologous recombination pathways and utilize [[RAD1 homolog|RAD1]] and γ[[H2AX]], which recognize double strand breaks and modify [[chromatin]], respectively. As a result, double strand breaks in meiotic cells, unlike mitotic cells, do not typically lead to [[apoptosis]], or cell death.<ref name="DNA damage">{{cite journal |vauthors=Matulis S, Handel MA |title=Spermatocyte responses in vitro to induced DNA damage |journal=Molecular Reproduction and Development |volume=73 |issue=8 |pages=1061–72 |date=August 2006  |pmid=16700071 |doi=10.1002/mrd.20508|s2cid=21185220 }}</ref> [[Homologous recombination]]al repair (HRR) of double-strand breaks occurs in mice during sequential stages of [[spermatogenesis]] but is most prominent in spermatocytes.<ref name="pmid16989005">{{cite journal |vauthors=Srivastava N, Raman MJ |title=Homologous recombination-mediated double-strand break repair in mouse testicular extracts and comparison with different germ cell stages |journal=Cell Biochem. Funct. |volume=25 |issue=1 |pages=75–86 |year=2007 |pmid=16989005 |doi=10.1002/cbf.1375 |s2cid=24830710 }}</ref> In spermatocytes, HRR events occur mainly in the pachytene stage of meiosis and the [[gene conversion]] type of HRR is predominant, whereas in other stages of spermatogenesis the reciprocal exchange type of HRR is more frequent.<ref name="pmid16989005" /> During mouse spermatogenesis, the [[mutation]] frequencies of cells at the different stages, including pachytene spermatocytes, are 5 to 10-fold lower than the mutation frequencies in [[somatic cell]]s.<ref name="pmid9707592">{{cite journal |vauthors=Walter CA, Intano GW, McCarrey JR, McMahan CA, Walter RB |title=Mutation frequency declines during spermatogenesis in young mice but increases in old mice |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue=17 |pages=10015–9 |year=1998 |pmid=9707592 |pmc=21453 |doi= 10.1073/pnas.95.17.10015|bibcode=1998PNAS...9510015W |doi-access=free }}</ref> Because of their elevated [[DNA repair]] capability, spermatocytes likely play a central role in the maintenance of these lower mutation rates, and thus in the preservation of the genetic integrity of the male germ line.

It is known that [[heterozygous]] chromosomal rearrangements lead to spermatogenic disturbance or failure; however the molecular mechanisms that cause this are not as well known. It is suggested that a passive mechanism involving asynaptic region clustering in spermatocytes is a possible cause. Asynaptic regions are associated with [[BRCA1]], kinase [[Ataxia telangiectasia and Rad3 related|ATR]] and γ[[H2AX]] presence in [[pachytene]] spermatocytes.<ref name="Spermato failure">{{cite journal |vauthors=Sciurano RB, Rahn MI, Rey-Valzacchi G, Coco R, Solari AJ |title=The role of asynapsis in human spermatocyte failure |journal=International Journal of Andrology |volume=35 |issue=4 |pages=541–9 |date=August 2012  |pmid=21977946 |doi=10.1111/j.1365-2605.2011.01221.x|doi-access=free }}</ref>

==Specific mutations==
[[File:Repro4 mutation in Spermatocytes.jpg|thumb|Wild-type spermatocyte progression compared to ''repro4'' mutated spermatocytes.|alt=]]
The gene Stimulated By Retinoic Acid 8 (''STRA8'') is required for the retinoic-acid signaling pathway in humans, which leads to [[meiosis]] initiation. ''STRA8'' expression is higher in preleptotene spermatocytes (at the earliest stage of [[prophase I]] in meiosis) than in [[spermatogonia]]. ''STRA8''-mutant spermatocytes have been shown to be capable of meiosis initiation; however, they cannot complete the process. Mutations in [[leptotene]] spermatocytes can result in premature chromosome condensation.<ref name=STRA8>{{cite journal|last=Mark|first=Manuel |author2=Hugues Jacobs |author3=Mustapha Oulad-Abdelghani |author4=Christine Dennefeld |author5=Betty Feret |author6=Nadege Vernet |author7=Carmen-Alina Codreanu |author8=Pierre Chambon |author9=Norbert Ghyselinck|title=STRA8-deficient spermatocytes initiate, but fail to complete, meiosis and undergo premature chromosome condensation|journal=Journal of Cell Science|date=7 July 2008|volume=121|pages=3233–3242 |issue=19|doi=10.1242/jcs.035071 |pmid=18799790|doi-access=free }}</ref>

Mutations in ''Mtap2'', a [[microtubule-associated protein]], as observed in ''repro4'' mutant spermatocytes, have been shown to arrest spermatogenesis progress during the prophase of [[meiosis I]]. This is observed by a reduction in [[spermatid]] presence in ''repro4'' mutants.<ref name=Mtap2>{{cite journal|last=Sun|first=Fengyun|author2=Mary Ann Handel |title=A Mutation in Mtap2 is Associated with Arrest of Mammalian Spermatocytes before the First Meiotic Division|journal=Genes|date=10 January 2011|volume=2|pages=21–35 |issue=1|doi=10.3390/genes2010021|pmid=24501684|pmc=3909985|doi-access=free}}</ref>

Recombinant-defective mutations can occur in ''[[Spo11]]'', [[DMC1 (gene)|''DMC1'']], [[Ataxia telangiectasia mutated|''ATM'']] and ''[[MSH5]]'' genes of spermatocytes. These mutations involve double strand break repair impairment, which can result in arrest of [[spermatogenesis]] at stage IV of the seminiferous epithelium cycle.<ref name="Recomb defects">{{cite journal|last=Barchi|first=Marco|author2=S. Mahadevaiah |author3=M. Di Giacomo |author4=F. Baudat |author5=D. de Rooij |author6=P. Burgoyne |author7=M. Jasin |author8=S. Keeney |title=Surveillance of Different Recombination Defects in Mouse Spermatocytes Yields Distinct Responses despite Elimination at an Identical Developmental Stage|journal=Molecular and Cellular Biology|date=August 2005|pages=7203–7215 |pmc=1190256 |pmid=16055729 |doi=10.1128/MCB.25.16.7203-7215.2005 |volume=25 |issue=16}}</ref>

==History==
[[File:Meiosis (248 23).jpg|thumb|Meiosis in Grasshopper testes (primary spermatocytes in zygotene, pachytene, prophase I).]]
The [[spermatogenesis]] process has been elucidated throughout the years by researchers who divided the process into multiple stages or phases, depending on [[intrinsic]] (germ and Sertoli cells) and [[extrinsic]] (FSH and LH) factors.<ref name="spermato and cycle of semi epit">{{cite book|editor-last=Cheng|editor-first=C. Yan|title=Molecular mechanisms in spermatogenesis|year=2008|publisher=Springer Science+Business Media|location=New York|isbn=978-0-387-79990-2|pages=Chapter 1, page 1|url=https://archive.org/details/molecularmechani00cych|url-access=registration}}</ref> The spermatogenesis process in mammals as a whole, involving cellular transformation, mitosis, and meiosis, has been well studied and documented from the 1950s to 1980s. However, during the 1990s and 2000s researchers have focused around increasing understanding of the regulation of spermatogenesis via genes, proteins, and signaling pathways, and the biochemical and molecular mechanisms involved in these processes. Most recently, the environmental effects on spermatogenesis have become a focus as [[male infertility]] in men has become more prevalent.<ref name="Spermatog history">{{cite journal|last=Cheng|first=C. Yan|author2=Dolores D. Mruk |title=The biology of spermatogenesis: the past, present and future|journal=Phil. Trans. R. Soc. B|date=19 April 2010|volume=365|series=1546|pages=1459–1463|issue=1546|doi=10.1098/rstb.2010.0024|pmid=20403863|pmc=2871927}}</ref>

An important discovery in the spermatogenesis process was the identification of the seminiferous epithelial cycle in mammals—work by C.P. Leblound and Y. Clermont in 1952 that studied the spermatogonia, spermatocyte layers and spermatids in rat seminiferous tubules. Another critical discovery was that of the hypothalamic-pituitary-testicular hormone chain, which plays a role in spermatogenesis regulation; this was studied by R. M. Sharpe in 1994.<ref name="Spermatog history" />

==Other animals==
[[File:Mesostoma ehrenbergii.jpg|thumb|right|''[[Mesostoma ehrenbergii]]'']]Primary [[cilia]] are common [[organelles]] found in [[eukaryotic cells]]; they play an important role in development of animals. ''Drosophila'' have unique properties in their spermatocyte primary cilia—they are assembled by four [[centrioles]] independently in the [[G2 phase]] and are sensitive to [[microtubule]]-targeting drugs. Normally, primary cilia will develop from one centriole in the G0/G1 phase and are not affected by microtubule targeting drugs.<ref name="Unique">{{cite journal |vauthors=Riparbelli MG, Cabrera OA, Callaini G, Megraw TL |title=Unique properties of Drosophila spermatocyte primary cilia |journal=Biology Open |volume=2 |issue=11 |pages=1137–47 |year=2013 |pmid=24244850 |pmc=3828760 |doi=10.1242/bio.20135355}}</ref>

''[[Mesostoma ehrenbergii]]'' is a [[Rhabdocoela|rhabdocoel]] [[flatworm]] with a distinctive male [[meiosis]] stage within the formation of spermatocytes. During the pre-anaphase stage, cleavage furrows are formed in the spermatocyte cells containing four univalent [[chromosomes]]. By the end of the [[anaphase]] stage, there is one at each pole moving between the spindle poles without actually having physical interactions with one another (also known as distance segregation). These unique traits allow researchers to study the force created by the spindle poles to allow the chromosomes to move, cleavage furrow management and distance segregation.<ref name="Meiosis in Mesostoma e">{{cite journal |vauthors=Ferraro-Gideon J, Hoang C, Forer A |title=Meiosis-I in Mesostoma ehrenbergii spermatocytes includes distance segregation and inter-polar movements of univalents, and vigorous oscillations of bivalents |journal=Protoplasma |volume=251 |issue=1 |pages=127–43 |date=January 2014  |pmid=23921676 |doi=10.1007/s00709-013-0532-9|s2cid=59941923 }}</ref><ref name="Mesostoma e spermatocyte">{{cite journal |vauthors=Ferraro-Gideon J, Hoang C, Forer A |title=Mesostoma ehrenbergii spermatocytes--a unique and advantageous cell for studying meiosis |journal=Cell Biology International |volume=37 |issue=9 |pages=892–8 |date=September 2013  |pmid=23686688 |doi=10.1002/cbin.10130|hdl=10315/38106 |s2cid=13210761 |hdl-access=free }}</ref>

== See also ==
*[[Germ cells]]
*[[Gametes]]
*[[Gametocytogenesis (disambiguation)|Gametocytogenesis]]
*[[Leydig]]
*[[Mitosis]]
*[[Meiosis]]
*[[Sertoli cells]]
*[[Spermatogenesis]]
*[[Spermatogonia]]
*[[Spermatid]]
*[[Spermatocytogenesis]]
*[[Spermatidogenesis]]
*[[Sperm]]

==References==
{{Reflist}}

==External links==
*[http://www.embryology.ch/anglais/cgametogen/spermato01.html Spermatogenesis]
*[https://web.archive.org/web/20140419215338/http://wps.aw.com/bc_goodenough_boh_3/104/26721/6840825.cw/content/index.html The Male Reproductive System]
*[http://classes.midlandstech.edu/carterp/Courses/bio211/Chap27/Reproductive_System.html The Reproductive System]
{{Male reproductive system}}

[[Category:Germ cells]]
[[Category:Mammal male reproductive system]]