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The Developmental Process of Spermatogenesis

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Dalia Khalife Ali Khalil

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Avens Publishing Group Goetz Egloff1*, Isabella Bender2, and Jasmin
Open Access Review Article
Invi t ing Innova t ions
J Androl Gynaecol Roemer3
October 2019 Vol.:7, Issue:1
© All rights are reserved by Ghina. Journal of
Andrology &
The Developmental Pro- Gynaecology
cess of Spermatogen- Dalia K1, Ali K2 and Ghina G1*

esis
1Department of Obstetrics and Gynecology, American University of
Beirut Medical Center, Lebanon
2Division of Gynecologic Oncology, American University of Beirut
Medical Center, Lebanon

Keywords: Spermatogenesis; Spermiation; Spermiogenesis; Sertoli *Address for Correspondence

cells Ghazeeri G, Division of Reproductive Endocrinology and Infertility,
Department of Obstetrics & Gynecology, American University of Beirut
Abstract Medical Center, Hamra, Beirut, PO BOX: 113-6044 Lebanon, Telephone:
01-350000, E-mail: [email protected]
The multiplication and development of germ cells in the
seminiferous tubules of the testiclesoccur through a complex series of Submission: 25 September, 2019
cellular events that are controlled by multiple signals. It is composed of Accepted: 9 October, 2019
6 stages in humans (Figure 1). Published: 18 October, 2019
Copyright: © 2019 Dalia K. This is an open access article distributed
Spermatogonial stem cells are self-renewed via mitosis, meiosis under the Creative Commons Attribution License, which permits
and contribute to the formation of haploid spermatids from diploid unrestricted use, distribution, and reproduction in any medium, provided
spermatocytes. Through the process of spermiogenesis, spermatids the original work is properly cited.
undergo maturation and are transformed into functional spermatozoa
which are released at spermiation after the breakage of intercellular
bridges attaching the spermatids to Sertoli cells. Spermatogenesis is
spermatogenesis [7].
a continuous process requiring the contribution of numerous cell and
regulatory factors. Its understanding is essential in order to advance
The Blood-Testis Barrier (BTB) is situated within the basement
research for treatment of male infertility. The different stages of membrane of the ST, providing the microenvironment for the
spermatogenesis along with the main roles of Sertoli cell and BTB will emergence of spermatids [8]. This barrier is well established at
be reviewed. Some emerging fields in research regarding the new puberty, concomitantly with the onset of meiosis [9]. The basal and
classification was briefly examined for a better understanding of the
complexity of the process. the ad-luminal compartments are the compartments found in the
Seminiferous Epithelium (SE) which are separated by the BTB. The
basal compartment includes undifferentiated spermatogonia (A and
B) and preleptotene spermatocytes. The ad-luminal compartment
Introduction is inhabited by the primary, secondary spermatocytes, haploid
spermatids and spermatozoa. During the 6 stages of spermatogenesis,
Spermatogenesis is a process occurring in the Seminiferous
the junctions between Sertoli cells and reproductive cells are in a
Tubules (ST) of the testicles. The multiplication and development of
constant remodeling process to allow transportation through the
germ cells occur through a complex series of cellular events that are
SE. It is in the ad-luminal compartment that meiosis I and II, the
controlled by multiple signals. While fourteen stages are found in rats,
formation up to the spermatozoa stage and spermiation take place
the seminiferous epithelial cycle is composed of 6 stages in humans
[10].
[1]. Spermatogonial stem cells are self-renewed via mitosis, meiosis
(I and II) and contribute to the formation of haploid spermatids The different stages of the epithelial cycle
from diploid spermatocytes. Through the process of spermiogenesis,
In humans, spermatogonia enter spermatogenesis every 16
spermatids undergo maturation and are transformed into functional
days, divide in a continuous way through mitosis to produce
spermatozoa which are released at spermiation after the breakage of
different variety of cells. This is entitled “cycle of the seminiferous
intercellular bridges attaching the spermatids to Sertoli cells [2,3].
epithelium” [11]. The detail inspection of cross sections of tubules
Intra-testicular and extra-testicular regulatory hormones involving
over the years uncovered 6 main stages of spermatogenesis or cellular
the release of Follicle Stimulating Hormone (FSH) from pituitary and
associations[12].
testosterone from leydig cells are the prime components of a well-
organized spermatogenesis [4]. Sertoli cells control the milieu within Cycle of the Seminiferous Epithelium
the seminiferous tubules in order to facilitate the progression of germ
The epithelial cycle is composed of 6 different stages along the
cells to spermatozoa. Hense, spermatogenesis is regulated through
SE of the testis [13]. A stage refers to a specific segment of the SE
the control of FSH on Sertoli cells and LH on Leydig cells.
over time [14]. The duration of spermatogenesis is around 64 days in
The seminiferous epithelium and hormonal regulation which a type A spermatogonia is transformed into multiple haploid
spermatozoa [15]. In this context, an epithelial cycle takes 16 days to
The testis is composed of 400 to 600 ST, which is the functional
be completed, yet it takes four cycles for a spermatogonia to become
unit of the test is where 300 million sperms per day are produced
a spermatid along the section of a tubule (74 days).
after puberty [5]. Sertoli cells have a significant role in supporting the
growth of the gonadal cells and thus are known as the ‘nurse’ cells Spermatogonial proliferation and spermatocytes formation
[6]. Leydig cells in return, under the influence of LH, supports the
Two types of spermatogonia (A and B) are present in the basal
production of testosterone necessarily for the step by step process of

Citation: Dalia K, Ali K, Ghina G. The Developmental Process of Spermatogenesis. J Androl Gynaecol. 2019;7(1): 3.
Citation: Dalia K, Ali K, Ghina G. The Developmental Process of Spermatogenesis. J Androl Gynaecol. 2019;7(1): 3.

ISSN: 2332-3442

over of homologous chromosomes [17]. Lactate is the main energy

source of spermatocytes which is metabolized by the Sertoli cells
via glucose transporters (GLUT1). This mechanism is controlled by
a close regulation between gonadotrophins, steroids and paracrine
factors [22].
Spermatids, spermiogenesis and spermiation
Four haploid spermatids are the products of the two meiotic
divisions of each spermatocyte.
Spermiogenesis is the process during which spermatids are
transformed into spermatozoa. Different techniques of staining were
used over the years to describe the formation of human spermatids
[11]. Nuclear characteristics of spermatids were described by Holstein
& Roosen by using glutaraldehyde fixation and toluidine blue stain.
Subsequently, they were able to detect 6 main stages (Sa, Sb1, Sb2, Sc,
Sd1, and Sd2) including morphological changes during which an
acrosomic granule is produced in the Golgi apparatus and grows
Figure 1: The six stages of the seminiferous epithelial cycle (I-VI) in the
human testis (Picture copied from Chen et al. 2017). over the nucleus. Additional changes happen, including: acrosome
formation, condensation of nuclear chromatin, detachment of
the cytoplasm forming the residual body, which is subsequently
compartment of the ST. Spermatogonia Ad (A dark type) and Ap
digested by Sertoli cells via phagocytosis, and finally the formation
(A pale type) represent type A spermatogonia. Spermatogonia
of a mature spermatozoon [23]. Any disruption at the level of the
Ap have a self-renewal property and thus are predominant while
acrosome formation, nucleus and/or flagellum maturation may lead
spermatogonia Ad are observed as the regenerative reserve of stem
to maturational arrest or hypospermatogenesis [24]. All these stages
cells [12,16]. On the other hand, B type spermatogonia characterize
are still within the premises of the human testis.
the beginning of reproductive cell growth up to the spermatids stage.
The multiplication of spermatogonia is synchronous through mitosis Spermiation is the final process during which mature spermatozoa
where the divided cells communicate via cytoplasmic bridges that are delivered into the lumen of ST for their subsequent maturation in
dissolve at the spermatids stages [17]. the epididymis. The delivery of matured spermatids is achieved via
the Sertoli cells during which they separate from their connections
The multiplication and differentiation of these cells is regulated by
and become spermatozoa [25]. Residual bodies including parts
the tyrosine kinase receptor (cKIT) protein which is only manifested
of the spermatids are digested into the Sertoli cells. The molecular
in spermatogonia, round spermatids and spermatozoa. Its ligand
mechanism is still poorly understood yet, it is dependent on FSH and
(cKIT ligand) is found at the level of Sertoli cells [18]. Retinoic acid
testosterone [26].
is involved in the commencement of meiosis and the conversion of
undifferentiated spermatogonia into type A spermatogonia [19]. Spermatozoa
Data in the literature is inconsistent about the stage of appearance The final product of spermatogenesis is the spermatozoa. The
of spermatogonia B. Clermont documented that that these cells were unique shape of spermatozoa permits its precise contact with the
formed between stages VI and I, evident in stages I and II and divide oocyte: nucleus is condensed, protected by an acrosome and attached
into preleptotene spermatocytes in the late stage II [11]. After the to a flagellum to allow progressive motility. The motility is acquired
ultimate spermatogonial division, cells undergo 2 stages of meiosis. during the transport in the epididymal ducts, depending on the
A pair of spermatogonia Ap produces 8 preleptotene spermatocytes normal development of axonemes, presence of mitochondria and
[20]. implantation of flagellum at the nucleus [23]. To note that the highly
condensed spermatozoa has a particular form of DNA packaging in
Stage III of the epithelial cycle represents the differentiation
the sperm nuclei where loops are packed as doughnuts, thus allowing
of spermatogonia B into preleptotene spermatocytes, which are
the transfer of the genome in a compacted form to the zygote [27].
shifted past the BTB while converting to leptotene spermatocytes.
Thus, after the initiation of meiosis at puberty, spermatocytes are Generations of differentiated germ cells are illustrated from the
located in the SE at different stages: leptotene, zygotene, pachytene, basement membrane upward to the tubule lumen. Spermatogonia
and diplotene [21]. During meiosis I, diplotene spermatocytes are are established in stage V, present in all cellular associations. The
transformed into secondary spermatocytes (1N:2C) which are then preleptotene spermatocytes appear during stage III, are transported
transformed into two round spermatids (1N:1C) via meiosis II. To through the BTB, to undergo meiosis during the stage IV of the
note that primary spermatocytes start their meiosis in the basal cycle. Newly formed spermatids are present in stage I with spherical
compartment of SE at the leptotene stage and reach the adluminal nucleus. It is till the end of stage II that spermiation is noted.
compartment through the BTB to proceed with further stages of
Different methods were used to precisely characterize the
division into secondary spermatocytes. Meiosis I involve DNA
morphology of germ cells within the SE. The present descriptions
replication, condensation of chromosomes, pairing and crossing
are based on initial studies done during the early 60s [11]. Although,

J Androl Gynaecol 7(1): 3 (2019) Page - 02

Citation: Dalia K, Ali K, Ghina G. The Developmental Process of Spermatogenesis. J Androl Gynaecol. 2019;7(1): 3.

ISSN: 2332-3442

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