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SPERMATOGENESISSTAGES, MECHANISM AND CONTROL

Spermatogenesis is the biological process of gradual transformation of germ cells into spermatozoa over an extensive period of time within the boundaries of the seminiferous tubules of the testis. This process involves cellular proliferation by repeated mitotic divisions, duplication of chromosomes, and genetic recombinations through crossover reduction division by meiotic division to produce haploid spermatids and terminal differentiation of the spermatids into spermatozoa. Thus spermatogenesis can be divided into three phases of proliferation, reduction-division (meiosis) and differentiation. These phases are also associated with specific germ cell types, i e spermatogonia, spermatocytes and spermatids respectively.

Spermatogenesis occurs within extensive seminiferous tubular structures, the testes. Seminiferous tubules are lined by the seminiferous epithelium and contain a fluid filled lumen; into which fully formed spermatozoa are released. The seminiferous epithelium consists of two basic cells types, somatic and germinal cells. The germ cells are found at different levels from the base of the epithelium tubules to the lumen and are surrounded by cytoplasm of somatic cell, the sertoli cells. Sertoli cell cytoplasm extends the entire height of the epithelium because the cell serves to nurture the germ cells through their cycles of development. As the germ cells divide and develop into different types of cells, they move from the basement membrane region through tight functional complexes of adjacent sertoli cells until they reside in the adluminal compartment. The Sertoli-Sertoli cell junctions form the blood-testis barrier, which helps to protect the developing germ cells from potentially harmful blood borne chemicals. The germ cells develop as syncytium or clonal unit connected to one another by intercellular bridges after cell division. This unique process of incomplete division ensures synchronous development and permits rapid communication between the cells. Synchrony of germ cell development results in large number of cells at the same level of development, the specific identification of which scientists refer to as stages.

PHASES OF SPERMATOGENESISProliferationProliferation spermatogonia, which constitute the first phase, are the most immature cells and are located along the base of the seminiferous epithelium. They proliferate by mitotic division and multiply repeatedly continually replenish the germinal epithelium. Spermatogonia are capable of self-renewal and thus also produce stem cells that remain along the base as well as committed cells that are on one-way tract leading to spermatozoa. In most species, the B spermatogonium is the last one to divide by mitosis. Its division produces the first cell of the second phase, the preleptotene spermatocyte, which migrates upwards away from the base of the seminiferous tubule and crosses through the sertoli-sertoli junction.

MeiosisReduction division by meiosis involves numerous types of spermatocytes that range in size from cells smaller than a red blood cell to very large that occupy portions of every cross section of seminiferous tubules. Reduction division is a biological mechanism by which a single germ cell can increase its DNA content, then divide twice to produce

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four individual germ cells containing a single strand of each chromosome or half the number of chromosomes normally found in cells of the body. The process of meiosis is extended over a long period of time; therefore' spermatocytes are found in every stage of spermatogenesis, and in some stages two different types; of spermatocytes are observed. During meiosis, the changes that take place in the chromosomes are easily recognized .DNA synthesis occurs in pre-leptotene spermatocytes. Prophase of the first meiotic division may, last nearly 3 weeks; during which time other chromosomes first unravel as thin unpaired filaments. Homologous chromosomes become paired in the zygote cell, forming the synaptonemal complex Pachytene spermatocytes begin as small cells but their nuclei enlarge greatly as the chromosomes become shorter and thicken. Genetic recombination occurs through crossover between paired chromosomes. Pachytene cells also exhibit an increase in RNAs and protein synthesis in preparation for the next phase. Diplotene spermatocytes separate the synaptonemal complexes and the chromosomes are spread apart in the nucleus. In diakinesis the nuclear envelope disappears and chromosomes condense. Both meiotic divisions occur rapidly, thus limiting these cell to one stage. Small secondary spermatocytes (2N) are produced by meiosis I which then rapidly divide again by meiosis II, with unique metaphase formations by the chromatin. Meiosis II produces very small haploid (1N) cells called round spermatids that enter the next phase called differentiation.DifferentiationThe haploid germ cells undergo a prolonged phase of terminal differentiation known as spermiogenesis. The cells undergo dramatic changes including the following three major modifications: (1) the nucleus elongates and chromatin condenses into a very dark staining structure having unique shapes that are species specific. (II) The Golgi apparatus produces a lysosome-like granule that elaborates over the nucleus to form the future acrosome. The acrosomic system contains the hydrolytic enzymes required for sperm-egg interaction and fertilization. and (III) the cells forms a long tail lined with mitochondria in the proximal region and it loses excess cytoplasm, which is added first as the cytoplasmic lobe that eventually is phagocytized by the sertoli cell as the residual body. Recognizable changes in the differentiation of a spermatid are called "steps" of spermiogenesis. In the rat, the first step is the small round step spermatid produced by meiosis II. Step I occurs in the first stage of the cycle. In all species, the tail elongate spermatids, steps 15-19 in the rat, overlap with the younger round spermatids thus, in some stages tow generation of spermatids are present in the same tubule cross section

PROCESSOnce the vertebrate primordial germ cells (PGC) arrive at the genital ridge of male in embryonic stage of development, they become incorporated in to the sex cords. They remain there until maturity, at which time the sex cords hollow out to form the

seminiferous tubules, and the epithelium of the tubules differentiates into the sertoli cells. These sertoli cells nourish and protect the developing sperm cells, and SPERMATOGENESIS- meiotic divisions giving rise to the sperm-occurs in the recesses of the sertoli cells. The process by which the PGCs generate sperm has been studied in detail in several organisms, but it shall be focused here on spermatogenesis in mammals. After reaching the gonad, the PGCs divide to form TYPE A1 SPERMATOGONIA. These cells

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are smaller than the PGCs and are characterized by an ovoid nucleus that contains chromatin associated with the nuclear membrane. The A1 spermatogonia are found adjacent to the outer basement membrane of the sex cords. At maturity, these spermatogonia are thought to divide so as to make another type A1 spermatogonium as well as a second, paler type of cell, the TYPE A2 SPERMATOGONIUM. Thus, each type A1 spermatogonium is a stem cell capable of regenerating itself as well as of producing a new cell type. The A2 spermatogonia divide to produce the A3 spermatogonia, which then beget the type A4 spermatogonia divide to form the TYPE B SPERMATOGONIA, and these cells divide mitotically to generate the PRIMARY SPERMATOCYTES-the cells that enter meiosis.

It is found that during the spermatogonial divisions, cytokinesis is not complete. Rather, the cells form a syncytium whereby each cell communicates to the other via. cytoplasmic bridges about 1 micron in diameter (Dym and Fawcett, 1971). The successive divisions produce clones of interconnected cells, and because ions and molecules readily pass through these intercellular bridges, each cohort, row of soldiers, matures synchronously.

Each primary spermatocyte undergoes the first meiotic division to yield a pair of SECONDARY SPERMATOCYTES, which complete the second division of meiosis. The haploid cells formed are called spermatids, and they are still connected to each other through their cytoplasmic bridges.

The spermatids that are connected in this manner have haploid nuclei, but are functionally diploid, since the gene product made in one cell can readily diffuse into the cytoplasm of its neighbors (Braun et al., 1989a). During the divisions from typeA1 spermatogonium to spermatids, the cells move farther and farther away from the basement membrane of the seminiferous tubule and closer to its lumen. Thus, each type of cell can be found in a particular layer of the tubule. The spermatids are located at the border of the lumen, and here they lose their cytoplasmic connections and differentiate into sperm cells.

SPERMIOGENESISThe haploid spermatid is a round, unflagellated cell that looks nothing like the mature vertebrate sperm. The next step in sperm maturation, then, is SPERMIOGENESIS (or SPERMATELIOSIS), the differentiation of the sperm cell. IN order for fertilization to occur, the sperm has to meet and bind with the egg, and spermiogenesis differentiates the sperm for these functions of motility and interaction. The first steps involve the construction of the acrosomal vesicle from the Golgi apparatus. The acrosome forms a cap that covers the sperm nucleus. As the cap is formed, the nucleus rotates so that the acrosomal cap will then be facing the basal membrane of the seminiferous tubule. This rotation is necessary because the flagellum is beginning to form from the centrioles on the other side of the nucleus, and this flagellum will extend into the lumen. During the last stage of spermiogenesis, the nucleus flattens and condenses, the remaining cytoplasm (the “cytoplasmic droplet”) is jettisoned, and the

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mitochondria from a ring around the base of the flagellum. The resulting sperm then enter the lumen of the tubule.

In the mouse, the entire development from stem cell to spermatozoan takes 34.5 days. The spermatogonial stages last 8 days, meiosis lasts 13 days, and spermiogenesis takes up another 13.5 days. In humans, spermatic development takes 74 days to complete. Because the type A1 spermatogonia are ///stem cells, spermatogenesis can occur continuously. Each hour, some 100 million sperm are made in each human testicle, and each ejaculation releases 200 million sperm. Unused sperm is either reabsorbed or passed out of the body in urine.

GENE EXPRESSION DURING SPERM DEVELOPMENTGene transcription during spermatogenesis takes place predominantly during the diplotene stage of meiotic prophase. This transcription has been observed in many organisms, but the documented case is probably that of Y chromosome transcription in Drosophila hydei. Here, RNA transcripts originating from the Y-chromosome are seen to be essential for controlling spermiogenesis. When we recall the function of the Y chromosome in Drosophila, this is not surprising, for the Y chromosome is not involved in sex determination here. Rather, it is needed for the formation of viable sperm. The difference between XY Drosophila and XO Drosophila is that the latter are sterile. Both are male. In Drosophila hydei, the Y chromosome extends five prominent loops of DNA .If any of these loops is deleted; the organization of the sperm tail will be abnormal. All the component parts of the sperm will be present, but not properly organized (Hess, 1973). It appears, then, that Y-specific RNA made during meiotic prophase is utilized later during spermiogenesis.

The genes that are transcribed specifically during spermatogenesis are often those whose products are necessary to sperm motility or binding to the egg. In Drosophila melanogaster, one of the sperm –specific genes transcribed is for b2-tubulin. This isoform of b-tubulin is only seen during spermatogenesis, and it is responsible for forming the meiotic spindles, the axoneme, and the microtubules associated with the lengthening mitochondria. Hoyle and Raff (1990) have shown that another b-tubulin isoform; b3-tubulin (which is normally expressed in mesodermal cells and epidermis) cannot substitute for the b2-tubulin. When this gene was expressed in the absence of the b2-tubulin gene, the resulting germ cells failed to undergo meiosis, axoneme assembly, or nuclear shaping. Only the mitochondrial elongation occurred. This indicates that the formation of the meiotic spindles and axoneme of sperm cells cannot be accomplished by just any b-tubulin and that the transcription of sperm-specific isoform is important.

Those genes whose products are necessary for the binding of the sperm and the extra cellular matrices of the egg are also transcribed during spermatogenesis. The gene for sea urchin bindin is transcribed relatively late in spermatogenesis and its m’RNA is translated into bindin shortly after being made (Nishioka et al., 1990). The bindin accumulates in vesicles that fuse together to form the single acrosomal vesicle of the mature sea urchin sperm.

Like the oocyte, the spermatid can store m’RNA for later use. In mammals and birds, a specific form of lactate dehydrogenate – SDH-X – is made during spermatogenesis. (This protein enables the developing sperm to utilize can be identified in spermatocyte cytoplasm during meiotic prophase (Blanco, 1980). Similarly, in many species, small proteins called PROTAMINES appear in the nucleus during the final stages of spermiogenesis. These proteins contain about 32 amino acids, all but four or five of which are arginine residues. They replace the nuclear histones and cause the DNA to form a compact, almost crystalline, array (Marushige and Dixon, 1969). DNA complementary to trout protamine m’RNA can detect protamine m’RNA can detect protamine message sequences in the primary spermatocyte. However, these messages are stored in ribonucleoprotein particles. Only during the spermatid stage, approximately a month after its synthesis is the protamine message translated into

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protein (Itarou et al., 1978). The regulation of this m’RNA appears to be controlled by its 3 untranslated region. If placed onto another message, this 3 untranslated region will give the new message, the same translational regulation as the protamines m’RNA. We find, then, that just like the oocyte, which can synthesize RNA in the diplotene stage and store it for late use, the sperm can also package messages for later translation.

In addition to gene transcription during meiotic prophase, there is also evidence that certain genes are transcribed in the spermatids (reviewed in Palmiter et al., 1984). This evidence for HAPLOID GENE EXPRESSION comes from studies involving heterozygous mice in which two different populations of sperm are seen to exist – one population expressing the mutant phenotype and one population expressing the wild-type trait. If the synthesis of the RNA or protein were to occur while the cells were still diploid, all the sperm would show the same phenotype.

In some species, sperm provides important developmental information that cannot be compensated by the egg. We have discussed the imprinting of mammalian chromosomes wherein the sperm and egg DNA differ in their methylation pattern. There are also cases of paternal effect genes. Here, homozygous recessive alleles in the male cause abnormal development in the embryo even if the female is homozygous for the wild-type allele, while the reciprocal cross, where the father is wild-type and the mother is homozygous for the mutant allele, leads to normal embryos. One such paternal effect gene is spe-11 in C. elegans. The sperm containing mutant alleles at the locus are unable to direct chromosomal movements that orient the mitotic spindle of the embryo, suggesting that the mutation affects the microtubule organizing regions such as centrioles.

Eventually, the haploid genome is condensed as the histones are replaced by protamines or by specifically modified histones. Many of the sperm histones become modified in the late spermatid stage during spermiogenesis. These modifications (such as dephosphorylating the N-terminal regions of certain histones) cause the chromatin to condense. Condensation results in severely reduced transcription. Thus, transcription from the male genome is not detected again until it is reactivated sometime during development (Poccia, 1986; Green and Poccia, 1988).

HORMONAL CONTROL OF SPERMATOGENESISThe production of spermatozoa and testosterone, is the primary functions of the adult mammalian testis, depends on stimulation of the testes by the gonadotropic hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Both hormones are produced by the pituitary gland in response to gonadotropin releasing hormone (GnRH) from the hypothalamus. In response to LH, testosterone is produced by the Leydig cells. It has been clear for decades that testosterone is a necessary prerequisite for the initiation of spermatogenesis in the peripubertal mammal, the maintenance of established spermatogenesis (and fertility) in adults induced experimentally to become oligospermic or azoospermic. It also is well established that FSH is involved in the peripubertal initiation of spermatogenesis. Whether or not FSH is also involved in regulating spermatogenesis in the adult mammal continues to be debated.

Although the effects of testosterone and FSH administration or with drawl on spermatogenesis have been studied for years, the mechanisms by which they regulate spermatogenesis remain uncertain. Androgen and FSH receptors are localized to sertoli cells, making it likely that the effects of both testosterone and FSH are mediated via. these cells. Over the past 10 years, it has become well established that the testosterone concentration normally present within the testis is very high relative to the concentration that should be required to saturate androgen receptors, and that although intratesticular testosterone concentration is also very high. There is no good explanation for this observation. Recent studies have shown that increased germ cell apoptosis occurs when testosterone is withdrawn from the mammalian testis, pointing

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to testosterone as a cell survival factor. The molecular mechanisms by which testosterone acts in this way only recently have begun to be considered. FSH also may act to prevent cell death, though this is less certain.

This article focuses on the roles of testosterone and FSH in mammalian spermatogenesis. Discussion will center on the relationship between intratesticular testosterone concentration and spermatogenesis, controversy regarding the requirement for FSH, and the possible mechanisms by which testosterone and FSH act to regulate spermatogenesis.

TESTOSTERONE AND FSH REQUIRED FOR SPERMATOGENESIS ?TestosteroneIn the rat, the concentration of testosterone in blood serum is approximately 2 ng/ml. Because Leydig cells are located in the interstitial compartment of the testis, it is not surprising that the concentrations of testosterone in the interstitial fluid (IF; 70ng/ml) and seminiferous tubule fluid (STF; 50ng/ml) of untreated rats are far greater than those in serum. Similar relationships between serum and intratesticular testosterone concentrations occur in the human. Interestingly, when testosterone is administered to rats in circumstances in which its local production by Leydig cells is suppressed, testosterone concentration does not equilibrate throughout the body, as might be expected; rather, a concentration gradient is established that is similar to the gradient that occurs normally, with testosterone concentration in IF>STF>serum. Thus, even when there is no local testosterone production, testosterone becomes concentrated within the testis. Whether or not administered testosterone also becomes concentrated in the human testis is not known

The average testosterone concentration in rat STF (50ng/ml; 1.7x10-7 M) is considerably higher than the Kp of testicular androgen receptors (3x10-9 M). This suggests that the testosterone concentration in the seminiferous tubules may be considerably in excess of that required to maintain established spermatogenesis in the adult rat. This was found experimentally to be the case. Zirkin and colleagues examined the quantitative relationship between intratesticular testosterone concentration and sperm number per testis in adult rats that received testosterone of increasing doses via testosterone filled Silastic capsules of increasing size. The administration of testosterone in this way suppresed Leydig cell testosterone production so that the only source of testosterone was from the capsules. Quantitatively complete spermatogenesis was maintained at a STF testosterone concentration of only 20 ng/ml resulted in graded reductions in sperm production, indicative of a dose response relationship between STF testosterone concentration and sperm produced by the testis. Similarly, in adult rats rendered azoospermic with a contraceptive dose of LH-suppressive testosterone, the intratesticular testosterone concentration found to be required for the restoration of quantitatively complete spermatogenesis also was 20 ng/ml. These observations indicate that spermatogenesis can be quantitatively maintained or restored at testosterone concentrations far lower than those normally present within the testis but still an order of magnitude greater than present in serum.

FSHThough the involvement of FSH in spermatogenesis has been studied extensively, considerable controversy remains about the circumstances in which it is required and what it does. The uncertainty stems in part from apparent species differences in the effects of FSH on spermatogenesis and in part from the time during the life cycle during which FSH is either administered or withdrawn. Numerous studies have shown that FSH is required (in addition to testosterone) for quantitatively normal spermatogenesis in adult nonhuman primates and humans and for testicular recrudescence in seasonally breeding rodents. There is also agreement that FSH is integrally involved in initiating spermatogenesis in immature rats. The receptor for FSH resides with the Sertoli cell. Given the effect of FSH on spermatogenesis initiation, it is not surprising that FSH elicits dramatic camp production by sertoli cells from

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prepubertal rat testes. Adult sertoli cells to FSH as rats approach adulthood. The altered sensitivity to FSH has been attributed in part to age related induction of phosphodiesterases, increased activity of G1 proteins, or induction of protein kinase inhibitors. Whatever the mechanism, it is apparent that the response of sertoli cells to FSH changes from the prepubertal to the adult period.

Controversy about the involvement of FSH in maintaining or restoring adult spermatogenesis has come largely from studies of the adult rat. The administration of testosterone to rats at the time of hypophysectomy, or after hypophysectomy-induced testicular regression, fails to maintain or restore spermatogenesis quantitatively, suggesting that pituitary factors in addition to LH may participate in the regulation of spermatogenesis. A number of studies of this kind have concluded that it is the absence of FSH, rather than the absence of other pituitary factors, that explains the inability of testosterone to sustain or restore spermatogenesis after hypophysectomy. Such a conclusion is consistent with studies showing synergy between FSH and testosterone effects in the adult. For example, the administration of recombinant FSH, by itself or together with testosterone, to hypophysectomized adult rats has been shown in some studies to prevent germ cell loss and in others to restore spermatogenesis (qualitatively) to germ cell depleted testes. The conclusion from such studies, taken together is that FSH can affect adult

Does FSH affect adult spermatogenesis under non-experimental conditions? Dym and colleagues reported that the administration of FSH antiserum to adult rats did not affect testis weight or germ cell number, concluding that FSH has little or no effect on spermatogenesis. Consistent with this, Awoniyi and colleagues reported that the administration of testosterone to adult rats at the time of their active immunization against GnRH maintained spermatogenesis quantitatively and, similarly, that testosterone alone, when administered to rats made azoospermic by active immunization against GnRH, restored spermatogenesis quantitatively in both cases in the absence of detectable FSH. If FSH remained suppressed throughout these immunization experiments, as Awoniyi and colleagues reported, these studies provide conclusive evidence that FSH is not required for the maintenance or restoration of spermatogenesis in adult rats. However, others have reported that at least some FSH is restored by testosterone treatment of GnRH-immunized rats. The issue has yet to be resolved.The arguments for and against a role for FSH in the adult rat might be reconciled by the thesis that under conditions in which intratesticular testosterone levels are high, FSH may not be required for either the maintenance of spermatogenesis or its restoration. In normal circumstances, total intratesticular testosterone concentration in fact is very high, typically more than twice the concentration found to be required to quantitatively maintain or restore spermatogenesis. In summary, available data suggest (1) that FSH may not be required for spermatogenesis in the normal adult rat because intratesticular testosterone concentrations normally are very high; but (2) that FSH can have significant effects on spermatogenesis when intratesticular testosterone concentrations fall. However, Griswold and colleagues reported that immunization of adult rats against the FSH receptor resulted in reduced sperm number, presumably despite normal high levels of testosterone. Moreover, in a setting in which there are defects in the genes encoding FSH and its receptor, spermatogenesis and fertility are possible. Thus, although the controversy regarding the role of FSH continues, it is becoming apparent that complete spermatogenesis can occur, and fertility can be realized, in the absence of FSH.

SPERMATOGENESIS IN A NUT SHELL WITH RESPECT TO HUMANS Spermatogenesis (sper’-ma-to-JEN-e-sis)In humans, spermatogenesis takes about 74 days. The seminiferous tubules are lined with immature cells called spermatogonia (sper’-ma-to-GO-ne-a; sperm = seed; gonium = generation or offspring. These cells develop from primordial (primordialis = primitive or early form) germ cells that arise from yolk sac endoderm and enter the

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testes early in development. In the embryonic testes, the primordial germ cells differentiate into spermatogonia but remain dormant until they begin to undergo mitotic proliferation at puberty. Spermatogonia contain the diploid (2n) chromosome number. When these stem cells undergo mitosis, some of the daughter cells remain undifferentiated and serve as a reservoir of stem cells. Such cells remain near the basement membrane. The rest of the daughter cells lose contact with the basement membrane of the seminiferous tubule, undergo certain developmental changes, and differentiate into primary spermatocytes (SPER-ma-to-sitz’). Primary spermatocytes, like spermatogonia, are diploid (2n); that is, they have 46 chromosomes.Reduction Division (Meiosis I) Each primary spermatocyte enlarges before dividing. Then two nuclear divisions take place as part of meiosis. In the first, DNA

replicates and 46 chromosomes (each made up of two identical chromatids) form and move toward the equatorial plane of the cell. There they line up in homologous pairs so that there are 23 pairs of duplicated chromosomes in the center of the cell. This pairing of homologous chromosomes is called synapsis. The four chromatids of each homologous pair then become associated with each other to form a tetrad. In a tetrad, portions of one chromatid may be exchanged with portions of another. This process, called crossing-over, permits an exchange of genes among chromatids those results in the recombination of genes. Thus the spermatozoa eventually produced are genetically unlike each other and unlike the cell that produced them-one reason for the great genetic variation among humans. Next, the meiotic spindle forms and the kinetochore microtubules produced by the centromeres of the paired chromosomes extend toward the poles of

the cell. As the pairs separate, members of each pair migrate to opposite poles of the dividing cell. The random assortment of maternally derived and paternally derived chromosomes toward opposite poles is another reason for genetic variation among spermatozoa and therefore among humans. The cells formed by the first nuclear division (reduction division) are called secondary spermatocytes. Each cell has 23 chromosomes – the haploid number. Each chromosome within a secondary spermatocyte, however, is made up of two chromatids still attached by a centromere. Equatorial Division (Meiosis II) The second nuclear division of meiosis is equatorial division. There is no replication of DNA. The chromosomes (each composed of two chromatids) line up in single file along the equatorial plane, and the chromatids of each chromosome separate from each other. The cells formed from the equatorial division are called spermatids. Each has half the original chromosome number, or 23 chromosomes, and is haploid. Each primary spermatocyte therefore produces four spermatids by meiosis (reduction division and equatorial division). Spermatids lie close to the lumen of the seminiferous tubule. During spermatogenesis, a very interesting and unique process occurs. As the sperm cells proliferate, they fail to complete cytoplasmic separation (cytokinesis) so that all the daughter cells, except for the least-differentiated spermatogonia, remain in contact via cytoplasmic bridges. These cytoplasmic bridges persist until development of the spermatozoa is complete, at which point they float out individually into the

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lumen of the seminiferous tubule. Thus the offspring of a spermatogonium remain in cytoplasmic communication through their entire development. This pattern of development undoubtedly accounts for the synchronized production of spermatozoa in any given area of a seminiferous tubule. It may have survival value in that half the spermatozoa contain an X chromosome and half a Y chromosome. The larger X-chromosome may carry genes needed for spermatogenesis that are lacking on the Y chromosome. Spermiogenesis The final stage of spermatogenesis, called spermiogenesis, involves the maturation of spermatids into spermatozoa. Each spermatid develops a head with an acrosome (enzyme-containing granule) and a flagellum (tail). Since there is no cell division in spermiogenesis, each spermatid develops into a single spermatozoon (sperm cell or sperm). The release of a spermatozoon from its sustentacular cell is known as spermiation. Sperm enter the lumen of the seminiferous tubule and migrate to the ductus epididymis. There, they complete their maturation in 10 to 14 days and become capable of fertilizing an ovum. Spermatozoa are also stored in the ductus (vas) deferens. Here, they can retain their fertility for up to several months.