Spermatogenesis

2 Location

Spermatogenesis is the process in which spermatozoa

are produced from male primordial germ cells by way of
mitosis and meiosis. The initial cells in this pathway are
called spermatogonia, which yield primary spermatocytes
by mitosis. The primary spermatocyte divides meiotically (Meiosis I) into two secondary spermatocytes; each
secondary spermatocyte divides into two spermatids by
Meiosis II. These develop into mature spermatozoa, also
known as sperm cells. Thus, the primary spermatocyte
gives rise to two cells, the secondary spermatocytes, and
the two secondary spermatocytes by their subdivision
produce four spermatozoa.[1]

Spermatogenesis takes place within several structures of

the male reproductive system. The initial stages occur within the testes and progress to the epididymis
where the developing gametes mature and are stored until
ejaculation. The seminiferous tubules of the testes are the
starting point for the process, where stem cells adjacent
to the inner tubule wall divide in a centripetal direction
beginning at the walls and proceeding into the innermost
part, or lumento produce immature sperm. Maturation
occurs in the epididymis. The location [Testes/Scrotum]
is specically important as the process of spermatogenesis requires a lower temperature to produce viable sperm,
specically 18 C lower than normal body temperature of 37 C (98.6 F).[3] Clinically, small uctuations in
temperature such as from an athletic support strap, causes
no impairment in sperm viability or count.[4]

Spermatozoa are the mature male gametes in many sexually reproducing organisms. Thus, spermatogenesis is
the male version of gametogenesis, of which the female
equivalent is oogenesis. In mammals it occurs in the
seminiferous tubules of the male testes in a stepwise fashion. Spermatogenesis is highly dependent upon optimal
conditions for the process to occur correctly, and is essential for sexual reproduction. DNA methylation and
histone modication have been implicated in the regu- 3 Duration
lation of this process.[2] It starts at puberty and usually
continues uninterrupted until death, although a slight deFor humans, the entire process of spermatogenesis is
crease can be discerned in the quantity of produced sperm
variously estimated as taking 74 days[5][6] (according to
with increase in age (see Male infertility).
tritium-labelled biopsies) and approximately 120 days[7]
(according to DNA clock measurements). Including the
transport on ductal system, it takes 3 months. Testes produce 200 to 300 million spermatozoa daily.[8] However,
1 Purpose
only about half or 100 million of these become viable
sperm.[9]
Spermatogenesis produces mature male gametes, commonly called sperm but specically known as spermatozoa, which are able to fertilize the counterpart female ga- 4 Stages
mete, the oocyte, during conception to produce a singlecelled individual known as a zygote. This is the cornerThe entire process of spermatogenesis can be broken up
stone of sexual reproduction and involves the two gametes
into several distinct stages, each corresponding to a parboth contributing half the normal set of chromosomes
ticular type of cell in human. In the following table,
(haploid) to result in a chromosomally normal (diploid)
ploidy, copy number and chromosome/chromatid counts
zygote.
are for one cell, generally prior to DNA synthesis and diTo preserve the number of chromosomes in the ospring vision (in G1 if applicable). The primary spermatocyte is
which diers between species each gamete must have arrested after DNA synthesis and prior to division.
half the usual number of chromosomes present in other
body cells. Otherwise, the ospring will have twice the
normal number of chromosomes, and serious abnormal- 4.1 Spermatocytogenesis
ities may result. In humans, chromosomal abnormalities
arising from incorrect spermatogenesis results in congeni- Main article: Spermatocytogenesis
Spermatocytogenesis is the male form of
tal defects and abnormal birth defects (Down Syndrome,
Klinefelters Syndrome) and in most cases, spontaneous gametocytogenesis and results in the formation of
abortion of the developing fetus.
spermatocytes possessing half the normal complement
1

STAGES

Each cell division from a spermatogonium to a spermatid

is incomplete; the cells remain connected to one another
by bridges of cytoplasm to allow synchronous development. It should also be noted that not all spermatogonia
divide to produce spermatocytes; otherwise, the supply
of spermatogonia would run out. Instead, certain types
of spermatogonia divide mitotically to produce copies of
themselves, ensuring a constant supply of spermatogonia
to fuel spermatogenesis.[10]

4.2 Spermatidogenesis
The process of spermatogenesis as the cells progress from primary spermatocytes, to secondary spermatocytes, to spermatids,
to Sperm

Main article: Spermatidogenesis

Spermatidogenesis is the creation of spermatids from secondary spermatocytes. Secondary spermatocytes produced earlier rapidly enter meiosis II and divide to produce haploid spermatids. The brevity of this stage
means that secondary spermatocytes are rarely seen in
histological studies.

4.3 Spermiogenesis
Main article: Spermiogenesis
During spermiogenesis, the spermatids begin to form a
tail by growing microtubules on one of the centrioles,
which turns into basal body. These microtubules form an
axoneme. The anterior part of the tail (called midpiece)
thickens because mitochondria are arranged around the
axoneme to ensure energy supply. Spermatid DNA also
undergoes packaging, becoming highly condensed. The
DNA is packaged rstly with specic nuclear basic proteins, which are subsequently replaced with protamines
during spermatid elongation. The resultant tightly packed
chromatin is transcriptionally inactive. The Golgi apparatus surrounds the now condensed nucleus, becoming the
acrosome.
Schematic diagram of Spermatocytogenesis

of genetic material. In spermatocytogenesis, a diploid

spermatogonium, which resides in the basal compartment of the seminiferous tubules, divides mitotically,
producing two diploid intermediate cells called primary
spermatocytes. Each primary spermatocyte then moves
into the adluminal compartment of the seminiferous
tubules and duplicates its DNA and subsequently undergoes meiosis I to produce two haploid secondary
spermatocytes, which will later divide once more into
haploid spermatids. This division implicates sources of
genetic variation, such as random inclusion of either
parental chromosomes, and chromosomal crossover, to
increase the genetic variability of the gamete.

Maturation then takes place under the inuence of

testosterone, which removes the remaining unnecessary
cytoplasm and organelles. The excess cytoplasm, known
as residual bodies, is phagocytosed by surrounding Sertoli cells in the testes. The resulting spermatozoa are now
mature but lack motility, rendering them sterile. The mature spermatozoa are released from the protective Sertoli
cells into the lumen of the seminiferous tubule in a process called spermiation.
The non-motile spermatozoa are transported to the
epididymis in testicular uid secreted by the Sertoli cells
with the aid of peristaltic contraction. While in the epididymis the spermatozoa gain motility and become capable of fertilization. However, transport of the mature
spermatozoa through the remainder of the male reproductive system is achieved via muscle contraction rather
than the spermatozoons recently acquired motility.

Role of Sertoli cells

Protect spermatids from the immune system of the

male, via the blood-testis barrier

8
7

5
7

4
3
2
1

Labelled diagram of the organisation of Sertoli cells (red) and

spermatocytes (blue) in the testis. Spermatids which have not yet
undergone spermination are attached to the lumenal apex of the
cell

Main article: Sertoli cell

The intercellular adhesion molecules ICAM-1 and

soluble ICAM-1 have antagonistic eects on the tight
junctions forming the blood-testis barrier.[12] ICAM-2
molecules regulate spermatid adhesion on the apical side
of the barrier (towards the lumen).[12]

6 Inuencing factors
The process of spermatogenesis is highly sensitive to uctuations in the environment, particularly hormones and
temperature. Testosterone is required in large local concentrations to maintain the process, which is achieved via
the binding of testosterone by androgen binding protein
present in the seminiferous tubules. Testosterone is produced by interstitial cells, also known as Leydig cells,
which reside adjacent to the seminiferous tubules.
Seminiferous epithelium is sensitive to elevated temperature in humans and some other species, and will be adversely aected by temperatures as high as normal body
temperature. Consequently, the testes are located outside
the body in a sack of skin called the scrotum. The optimal
temperature is maintained at 2 C (man)8 C (mouse)
below body temperature. This is achieved by regulation
of blood ow[13] and positioning towards and away from
the heat of the body by the cremasteric muscle and the
dartos smooth muscle in the scrotum.

At all stages of dierentiation, the spermatogenic cells

are in close contact with Sertoli cells which are thought
to provide structural and metabolic support to the developing sperm cells. A single Sertoli cell extends from the
basement membrane to the lumen of the seminiferous
tubule, although the cytoplasmic processes are dicult
to distinguish at the light microscopic level.
Dietary deciencies (such as vitamins B, E and A),
Sertoli cells serve a number of functions during spermato- anabolic steroids, metals (cadmium and lead), x-ray exgenesis, they support the developing gametes in the fol- posure, dioxin, alcohol, and infectious diseases will also
adversely aect the rate of spermatogenesis. In addition,
lowing ways:
the male germ line is susceptible to DNA damage caused
Maintain the environment necessary for develop- by oxidative stress, and this damage likely has a signicant impact on fertilization and pregnancy.[14] Exposure
ment and maturation, via the blood-testis barrier
to pesticides also aects spermatogenesis.[15]
Secrete substances initiating meiosis
Secrete supporting testicular uid

7 Hormonal control

Secrete androgen-binding protein (ABP), which

concentrates testosterone in close proximity to the
Hormonal control of spermatogenesis varies among
developing gametes
species. In humans the mechanism is not completely
Testosterone is needed in very high quantities understood; however it is known that initiation of sperfor maintenance of the reproductive tract, and matogenesis occurs at puberty due to the interaction of
ABP allows a much higher level of fertility
the hypothalamus, pituitary gland and Leydig cells. If
Secrete hormones aecting pituitary gland con- the pituitary gland is removed, spermatogenesis can still
trol of spermatogenesis, particularly the polypeptide be initiated by follicle stimulating hormone (FSH) and
testosterone.[16] In contrast to FSH, LH appears to have
hormone, inhibin
little role in spermatogenesis outside of inducing gonadal
Phagocytose residual cytoplasm left over from testosterone production.[16][17]
spermiogenesis
FSH stimulates both the production of androgen binding
Secretion of anti-Mllerian hormone causes deteri- protein (ABP) by Sertoli cells, and the formation of the
oration of the Mllerian duct[11]
blood-testis barrier. ABP is essential to concentrating

testosterone in levels high enough to initiate and maintain spermatogenesis. Intratesticular testosterone levels
are 20100 or 50200 times higher than the concentration found in blood, although there is variation over a 5to 10-fold range amongst healthy men.[18][19] FSH may
initiate the sequestering of testosterone in the testes, but
once developed only testosterone is required to maintain spermatogenesis.[16] However, increasing the levels
of FSH will increase the production of spermatozoa by
preventing the apoptosis of type A spermatogonia. The
hormone inhibin acts to decrease the levels of FSH. Studies from rodent models suggest that gonadotropins (both
LH and FSH) support the process of spermatogenesis by
suppressing the proapoptotic signals and therefore promote spermatogenic cell survival.[20]
The Sertoli cells themselves mediate parts of spermatogenesis through hormone production. They are capable of producing the hormones estradiol and inhibin.
The Leydig cells are also capable of producing estradiol in addition to their main product testosterone. Estrogen has been found to be essential for spermatogenesis in animals.[21][22] However, a man with estrogen insensitivity syndrome (a defective ER) was found produce sperm with a normal sperm count, albeit abnormally low sperm viability; whether he was sterile or not
is unclear.[23] Levels of estrogen that are too high can
be detrimental to spermatogenesis due to suppression of
gonadotropin secretion and by extension intratesticular
testosterone production.[24] Prolactin also appears to be
important for spermatogenesis.[17]

See also
Anisogamy
Evolution of sexual reproduction
Folliculogenesis
Germ cells
Male infertility
Meiosis
Oncofertility
Oogenesis
Origin and function of meiosis
Sertoli cells
Sexual reproduction
Semen analysis

REFERENCES

9 References
[1] The Spermatozon, in Grays Anatomy.
2010-10-07.

Retrieved

[2] Song, Ning; Liu, Jie; An, Shucai; Nishino, Tomoya; Hishikawa, Yoshitaka; Koji, Takehiko (2011).
Immunohistochemical Analysis of Histone H3 Modications in Germ Cells during Mouse Spermatogenesis. Acta Histochemica et Cytochemica 44 (4): 183
90. doi:10.1267/ahc.11027. PMC 3168764. PMID
21927517.
[3] scrotum. Encyclopdia Britannica. Encyclopdia Britannica Online. Encyclopdia Britannica Inc., 2015.
Web. 14 Jan. 2015 <http://www.britannica.com/
EBchecked/topic/530078/scrotum>.
[4] Wang C, McDonald V, Leung A, Superlano L, Berman
N, Hull L, Swerdlo RS (1997). Eect of increased
scrotal temperature on sperm production in normal men.
Fertil. Steril. 68 (2): 3349. doi:10.1016/s00150282(97)81525-7. PMID 9240266.
[5] Heller CG, Clermont Y (1964). Kinetics of the germinal
epithelium in man. Recent Prog Horm Res 20: 545571.
[6] Amann RP (2008). The cycle of the seminiferous epithelium in humans: a need to revisit?". J Androl 29
(5): 469487. doi:10.2164/jandrol.107.004655. PMID
18497337.
[7] Forster P, Hoho C, Dunkelmann B, Schrenkamp M,
Pfeier H, Neuhuber F, Brinkmann B (2015). Elevated
germline mutation rate in teenage fathers. Proc R Soc
B 282: 20142898. doi:10.1098/rspb.2014.2898. PMC
4345458. PMID 25694621.
[8] Padubidri, VG; Daftary, SN, eds. (2011). Shaws Textbook of Gynaecology (15th ed.). p. 201. ISBN 978-81312-2548-6.
[9] Johnson L, Petty CS, Neaves WB (1983). Further quantication of human spermatogenesis: germ cell loss during postprophase of meiosis and its relationship to daily
sperm production. Biol. Reprod. 29 (1): 20715.
doi:10.1095/biolreprod29.1.207. PMID 6615966.
[10] Fishelson, Lev; Gon, Ofer; Holdengreber, Vered; Delarea,
Yakob (2007). Comparative spermatogenesis, spermatocytogenesis, and spermato-zeugmata formation in males
of viviparous species of clinid shes (Teleostei: Clinidae,
Blennioidei)". The Anatomical Record 290 (3): 31123.
doi:10.1002/ar.20412. PMID 17525946.
[11] Hadley, Mac E.; Levine, Jon E. (2007). Endocrinology
(6th ed.). Upper Saddle River, NJ: Prentice Hall. p. 369.
ISBN 0-13-187606-6.
[12] Xiao, X.; Mruk, D. D.; Cheng, C. Y. (2013).
Intercellular adhesion molecules (ICAMs) and spermatogenesis. Human Reproduction Update 19 (2): 16786.
doi:10.1093/humupd/dms049. PMC 3576004. PMID
23287428.

[13] Harrison, RG; Weiner, JS (1949). Vascular patterns of

the mammalian testis and their functional signicance.
The Journal of Experimental Biology 26 (3): 30416, 2
pl. PMID 15407652.
[14] Lewis, SE; Aitken, RJ (2005). DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell
and tissue research 322 (1): 3341. doi:10.1007/s00441005-1097-5. PMID 15912407.
[15] Mehrpour, O; Karrari P (2014). Occupational exposure to pesticides and consequences on male semen
and fertility: A review.. Toxicol Lett 230: 146156.
doi:10.1016/j.toxlet.2014.01.029. PMID 24487096.
[16] William J. Kraemer; A. D. Rogol (15 April 2008). The
Encyclopaedia of Sports Medicine: An IOC Medical Commission Publication, The Endocrine System in Sports and
Exercise. John Wiley & Sons. pp. 286. ISBN 978-0470-75780-2.
[17] Fody EP, Walker EM (1985). Eects of drugs on the
male and female reproductive systems. Ann. Clin. Lab.
Sci. 15 (6): 4518. PMID 4062226.
[18] Wolf-Bernhard Schill; Frank H. Comhaire; Timothy B.
Hargreave (26 August 2006). Andrology for the Clinician.
Springer Science & Business Media. pp. 76. ISBN 9783-540-33713-3.
[19] Eberhard Nieschlag; Hermann M. Behre; Susan Nieschlag (26 July 2012). Testosterone: Action, Deciency,
Substitution. Cambridge University Press. pp. 130.
ISBN 978-1-107-01290-5.
[20] Pareek, Tej K.; Joshi, Ayesha R.; Sanyal, Amartya;
Dighe, Rajan R. (2007). Insights into male germ
cell apoptosis due to depletion of gonadotropins caused
by GnRH antagonists. Apoptosis 12 (6): 1085100.
doi:10.1007/s10495-006-0039-3. PMID 17268770.
[21] O'Donnell L, Robertson KM, Jones ME, Simpson ER
(2001). Estrogen and spermatogenesis. Endocr. Rev.
22 (3): 289318. doi:10.1210/edrv.22.3.0431. PMID
11399746.
[22] Carreau S, Bouraima-Lelong H, Delalande C (2012).
Role of estrogens in spermatogenesis. Front Biosci (Elite
Ed) 4: 111. PMID 22201851.
[23] Smith, Eric P.; Boyd, Je; Frank, Graeme R.; Takahashi, Hiroyuki; Cohen, Robert M.; Specker, Bonny;
Williams, Timothy C.; Lubahn, Dennis B.; Korach,
Kenneth S. (1994). Estrogen Resistance Caused by
a Mutation in the Estrogen-Receptor Gene in a Man.
New England Journal of Medicine 331 (16): 1056
1061. doi:10.1056/NEJM199410203311604. ISSN
0028-4793. PMID 8090165.
[24] Edmund S. Sabanegh, Jr. (20 October 2010). Male Infertility: Problems and Solutions. Springer Science & Business Media. pp. 83. ISBN 978-1-60761-193-6.

10 Further reading
The testes and spermatogenesis. University of
Wisconsin. 1998. Retrieved 2006-11-27.
Johnson, L.; Blanchard, T.L.; Varner, D.D.;
Scrutcheld, W.L. (1997). Factors aecting spermatogenesis in the stallion. Theriogenology 48 (7):
1199216. doi:10.1016/S0093-691X(97)00353-1.
PMID 16728209.
Bardin, C.W. (1991). Pituitary-testicular axis. In
Yen, S.S.C.; Jaee, R.B. Reproductive Endocrinology (3rd ed.). Philadelphia: WB Saunders. ISBN
0721632068.
Chambers, CV; Shafer, MA; Adger, H; Ohm-Smith,
M; Millstein, SG; Irwin Jr, CE; Schachter, J; Sweet,
R (1987). Microora of the urethra in adolescent
boys: Relationships to sexual activity and nongonococcal urethritis. The Journal of Pediatrics 110
(2): 31421. doi:10.1016/S0022-3476(87)801804. PMID 3100755.
Czyba, J.C.; Girod, C. (1980). Development of
normal testis. In Hafez, E.S.E. Descended and
Cryptorchid Testis. The Hague: Martinus Nijho.
ISBN 9024723337.
Whitmore Wf, 3rd; Karsh, L; Gittes, RF (1985).
The role of germinal epithelium and spermatogenesis in the privileged survival of intratesticular
grafts. The Journal of Urology 134 (4): 7826.
PMID 2863395.

11 External links
Spermatogenesis male reproductive physiology
Spermatogenesis animation

12

12
12.1

TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

Text and image sources, contributors, and licenses

Text

Spermatogenesis Source: https://en.wikipedia.org/wiki/Spermatogenesis?oldid=725919574 Contributors: Lexor, Julesd, Andres, Tristanb, Robbot, Yelyos, Caknuck, Diberri, GreatWhiteNortherner, Matt Gies, Kandar, Jutta, Roberdin, Rich Farmbrough, Bender235, Arcadian, Obradovic Goran, Abstraktn, Alansohn, Riana, Caesura, RyanGerbil10, 2004-12-29T22:45Z, Magister Mathematicae, Rjwilmsi,
Mirmillon, Klortho, FlavrSavr, Gsp, FlaBot, YurikBot, Wavelength, Chanlyn, RussBot, Chris Capoccia, Rsrikanth05, Voyevoda, D.
Wu, Nephron, Alex43223, Mieciu K, User27091, Lt-wiki-bot, Jonathan.s.kt, KnightRider~enwiki, Jrockley, Eskimbot, Bluebot, RDBrown, Octahedron80, Cregox, Richard0612, Mitsuki152, SashatoBot, Deepankar s, AmiDaniel, Heimstern, Lazylaces, LestatdeLioncourt,
TheAmelianator, Serephine, Citicat, Novangelis, MTSbot~enwiki, Grothmag, Andreas Rejbrand, High Elf, Dgw, DanielRigal, Shanew2,
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File:Figure_28_01_04.jpg Source: https://upload.wikimedia.org/wikipedia/commons/b/b1/Figure_28_01_04.jpg License: CC BY 3.0

Contributors: Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Original artist: OpenStax
College
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