4.5 times the duration of the cycle, that is 61 days. The durations of spermatocytogenesis, meiosis, and spermiogenesis are 21, 23, and 17 days, respectively [16].
The spermatogenic wave is “a sequence of segments showing the complete series of cell associations corresponding to the stages of the cycle of the seminiferous epithelium. One or more modulations must, however, be excluded from the sequence of the segments considered.” While the cycle of the seminiferous epithelium refers to the temporal arrangement of the germ cells at a given point of the ST, the spermatogenic wave refers to the spatial arrangement of germ cells along the ST [24]. However, the wave is not in space what the cycle is in time – the wave is not a dynamic process but is a static way to describe the spatial distribution of the associations along the tubule [16]. Spermatogenesis progresses along the ST in wave form, and the wave is formed by the fact that specific germ associations, i.e. stages, start again and again at specific distance. The regulated order of the wave emergence along the ST follows the numerical order of the stages of the cycle of the seminiferous epithelium [25, 26]. Different waves start as we move along the ST, and at a specific section of the ST, cells from different waves are seen together in a cross‐section of the ST according to the stage of the cycle of the seminiferous epithelium. The waves move along the ST in an inward spiral fashion, with A1 undifferentiated at the outer border of the wave and spermatozoa at the inner border of the wave. One spermatogenic wave starts with initiation of spermatogenesis, i.e. from conversion of type Aundifferentiated to type A1 differentiating spermatogonia under the repeated actions of retinoic acid, and ends with formation of spermatozoa [27]. Histologically, stages of the cycle are identified by two methods: (i) by meiotic status of spermatocytes and changes in the shape and position of nuclei of spermatids; or (ii) by differential morphology of the acrosome of spermatids [24].
Spermatogenesis in the Bull
Spermatogenesis in the bull establishes progressively from 16 weeks to 32 weeks of age. Gonocytes are the main germ cells in the ST until one week of age and are sequentially replaced by undifferentiated spermatogonia by 20 weeks. Meiosis starts at about 16 weeks and is completed by 28–32 weeks. Complete spermatogenesis can be observed in cross‐sections of the ST by 32 weeks of age [23].
Histologically, spermatogenesis is evaluated qualitatively by the appearance of the ST and quantitatively by differential cell count in the ST. Daily sperm production (DSP, millions) per gram of decapsulated testes is an appropriate measure of the efficiency of spermatogenesis and is used for species comparison [28]. DSP per gram of decapsulated testes is 4–6 for the human man, 12 for the bull, 16–19 for the stallion, 21 for the ram, 23 for the rhesus monkey and for the boar, 20–24 for the rat, 24 for the hamster, and 25 for the rabbit [28–30]. DSP is affected by longer duration of spermatogenesis, longer cycle of the seminiferous epithelium, the density of germ cells in the ST, and germ cell degeneration during spermatogenesis [30]. The reason for lower efficiency of spermatogenesis in the bull is not understood [16]. In the bull, germ cell degeneration during transition from A1 to A4 and at intermediate spermatogonia stage accounts for 30% losses in DSP. Moreover, degeneration at B1 and during transition from B1 to B2 causes another 30% loss. However, there is no loss during meiosis and spermiogenesis in the bull. In the absence of this degeneration, the bull would have a DSP of around 30 × 106/g of testes [16, 25].
When a bull can produce an ejaculate with 50 million spermatozoa with at least 10% motility, he is pubertal [31]. Age at puberty varies from 38 to 48 weeks of age, with an average age of 42 weeks [32]. After maturity, a bull can give two useable ejaculates daily; commercially, bull ejaculates are collected three times a week for a balance between management and number of artificial insemination doses. Both the quality and quantity of spermatogenesis decrease in old age; however, the aging‐related extinction of spermatogenesis in the bull has not been reported. Aging‐related decrease in sperm production has not been studied in the bull as breeding bulls are not maintained for senescence. One of the reasons for age‐related decline in spermatogenesis is decreased Sertoli cell number in old age [16].
Sertoli Cells and Spermatogenesis
Sertoli cells (SC) play an indispensable role in the regulation of spermatogenesis, establishing the rate of spermatogenesis, and in development and movement of germ cells [33, 34]. SC are one of the most complex and dynamic cells in biology [35].
The cell was first described by and hence named after Enrico Sertoli [36]. SC are large irregular shaped columnar cells extending from the base of the ST to the apex of the ST and occupy 17–19% volume of the tubule [34]. The large surface area of SC allows for interaction with an enormous number of germ cells as the SC to germ cell ratio in adult rats is about 1 : 50 [37]. SC are the most important somatic cells of testes and possess high plasticity synchronized with cyclic evolution of germ cells. The cells change their structure during their development and according to the cycle of the seminiferous epithelium. At any life point, SC of type A and type B are seen in the ST. Type A SC have cytoplasmic crypts for attachment of mature spermatids ready for release into the ST lumen. In type B SC such cytoplasmic crypts are less prominent or absent [38]. The SC nucleus is multilobed and the cytoplasm is rich in endoplasmic reticulum, glycoproteins, and cytoplasmic droplets; the cytoskeleton varies with the cycle of the seminiferous epithelium [39].
The Role of Sertoli Cells in Spermatogenesis
Structural Support
SC in association with peritubular myoid cells secrete basement membrane of the ST [40]. The cytoskeleton of SC participates in organizing and shaping the ST [41]. Major components of SC cytoskeleton are actin, intermediate filaments, and microtubules, and each has a unique distribution pattern according to different stages of the cycle of the seminiferous epithelium [42]. The functions of SC cytoskeleton include (i) maintaining SC shape; (ii) positioning and transporting organelles within the cell; (iii) forming and stabilizing SC membrane at sites of cell–cell and cell–extracellular matrix contact; (iv) positioning, anchoring, and aiding in the movement of developing germ cells; and (v) involvement in the release of mature spermatids from the ST during spermiation [34].
Blood–Testes Barrier
At puberty, neighboring SC develop tight junctions, forming an impermeable blood–testes barrier [40]. The barrier is a modified occluding junction located in the basal third of the seminiferous epithelium [43]. The blood–testes barrier divides the seminiferous epithelium into basal and adluminal compartments [44]. The basal part houses spermatogonia, preleptotene, and leptotene spermatocytes, while further advanced meiotic spermatocytes and spermatids reside in the adluminal part [34].
The blood–testes barrier shields germ cells in the adluminal part of the ST from direct contact with blood, protecting the cells from toxic, mutagenic, and autoimmune reactions. The barrier maintains specific concentrations of androgen‐binding protein, inhibin, activin, and enzyme inhibitors within the adluminal compartment of the ST. It controls transport of molecules and wastes to and from the adluminal compartment [45, 46]. The blood–testis barrier also functions as an immunological barrier to protect novel proteins at spermatocytes and spermatids from autoimmune reaction and inhibits immunoglobulins and lymphocytes from entering the adluminal part [35]. SC and germ cells produce interferons, interferon‐induced proteins, interleukins, and cytokines, which maintain an antiviral defense system [47].
Germ Cell Translocation
As germ cells lack the necessary architecture for migration, SC are responsible for germ cell migration across the seminiferous epithelium. SC assist in the translocation of preleptotene spermatocyte from the basal to adluminal compartment of the ST across the blood–testis barrier [34]. Specialized adhesion junctions, ectoplasmic specializations, of SC attach to the spermatid head and translocate spermatids up and down across the seminiferous epithelium. Ectoplasmic specializations consist of regions of SC plasma membrane adherent to the spermatid head, a submembrane layer of tightly packed SC actin filaments, and an attached