Читать книгу Bovine Reproduction - Группа авторов - Страница 86

The prepubertal period is characterized by a temporary increase in gonadotropin secretion, the so‐called early gonadotropin rise. The early gonadotropin rise is a critical event in the sexual development of bulls. Not only is it associated with dramatic changes in testicular cellular composition, initial increase in testosterone secretion, and timing of attainment of puberty, but also it has long‐lasting effects on testicular growth and sperm production. This period extends from approximately two to six months of age in B. taurus bulls.

The early gonadotropin rise is driven by increased GnRH pulse secretion, as demonstrated by a dramatic increase in LH pulse frequency (Figure 5.2); pulsatile discharges of follicle‐stimulating hormone (FSH) have been observed in bulls but are much less evident than those of LH. The number of LH pulses increases from less than one per day at one month to approximately 12–16 per day (one or more pulses every two hours) at approximately four months of age. Changes in pulse amplitude during this period are not consistent among reports; amplitude may be reduced, unchanged, or augmented [2, 7,18–21]. LH‐binding sites are present in testicular interstitial tissue at birth and at four months of age and pulsatile LH secretion is an essential requirement for Leydig cell proliferation, differentiation, and maintenance of fully cell differentiated structure and function [22]. Mesenchymal‐like cells in the testes cease to proliferate around four months of age and start to differentiate into contractile myofibroblasts and Leydig cells. Differentiating, mitotic, and degenerating Leydig cells are observed in close proximity from four to seven months of age. Leydig cell numbers and mass per testis increase from one month (0.42 billion and 0.15 g/testis, respectively) to seven months of age (6 billion and 5.8 g/testis, respectively), but mitosis after this age is rare [13, 14]. Circulating insulin‐like peptide 3 (INSL3), a major product and biomarker of Leydig cell functional capacity, increases linearly between two and six months in bulls [6, 23].

Figure 5.2 Serum LH concentrations between 10 and 30 weeks of age in Angus and Angus × Charolais bulls. Graphs closely exemplify the mean pulse frequency and pulse amplitude observed in bulls receiving adequate nutrition.

Sources: [2, 4, 6].

The characteristic pulsatile nature of LH secretion is important for testosterone production, since continuous exposure of Leydig cells to LH results in reduced steroidogenic responsiveness due to downregulation of LH receptors [24]. Initiation of Leydig cell steroidogenesis is characterized by increased androstenedione secretion, which decreases as the cells complete maturation and begin secreting testosterone. During the first three to four months of age, testosterone concentrations are low and secretion does not necessarily accompany LH pulses. After this age, LH pulses are followed by testosterone pulses and mean testosterone concentrations begin to increase. The number of testosterone pulses increases from 0.3–2.3 pulses per 24 hours at one to four months of age to 7.5–9 pulses per 24 hours at five months of age [25–28].

The crucial role of the LH secretion pattern during the early gonadotropin rise in regulating sexual development in bulls has been demonstrated in several studies using a variety of approaches. Prolonged treatment with a GnRH agonist in calves aged 1.5–3.5 months decreased LH pulse frequency, pulse amplitude, and mean concentrations at three months of age, delayed the peak mean LH concentration from five to six months of age, and reduced testosterone concentrations between 3.5 and 4.5 months of age. These hormonal alterations were associated with delayed puberty and reduced testes weight and number of germ cells in tubular cross‐sections at 11.5 months of age. On the other hand, treatment with GnRH every two hours to mimic pulsatile secretion from 1 to 1.5–2 months of age increased LH pulse frequency and mean concentration during the treatment period and resulted in greater scrotal circumference, testes weight, seminiferous tubules diameter, and number of germ and Sertoli cells in tubular cross‐sections at 12 months of age [29–31]. The LH secretion pattern during the prepubertal period is also associated with age at puberty in bulls raised in contemporary groups, suggesting that this is the physiological mechanism by which genetics affect sexual development. Studies have shown that LH pulse frequency was greater around 2.5–5 months of age and that mean LH concentrations increased earlier and reached greater maximum levels in early‐ than in late‐maturing Hereford bulls (age at puberty 9.5 and 11 months, respectively) [19, 21].

Additional support for the crucial role that LH secretion pattern during the early gonadotropin rise plays in sexual development in bulls has been provided by studies demonstrating that nutrition during the prepubertal period affects LH secretion pattern, age at puberty, and testicular development. In studies with beef and dairy bulls receiving different nutrition from 2 to 16 months of age, reduced LH pulse frequency during the prepubertal period resulted in delayed puberty in bulls receiving low nutrition, while a more sustained increase in LH pulse frequency in bulls receiving high nutrition was associated with hastened testosterone production and greater testes weight at 16–19 months of age when compared with bulls receiving low and medium (control) nutrition (results in beef bulls are shown in Figure 5.3). These observations were corroborated by additional studies designed to investigate the effects of nutrition specifically during the prepubertal period. Bulls that received high nutrition only from two to seven months of age also had a more sustained increase in LH pulse frequency, had greater testosterone secretion, were approximately two to four weeks younger at puberty, and had greater testes weight at 16–19 months of age when compared with bulls receiving control nutrition (results in beef bulls are shown in Figure 5.4). On the other hand, reduced LH secretion resulting from low nutrition from two to six months of age was associated with increased age at puberty and smaller testes weight at 16–19 months of age even when these bulls received control or high nutrition after seven months of age and LH and testosterone secretion were not different after the change in nutrition (results in beef bulls are shown in Figure 5.5) [2–4,32–35].

Figure 5.3 Mean (± SEM) number of LH pulses and serum testosterone concentrations in Angus and Angus × Charolais bulls receiving low, medium (control), or high nutrition from 10 to 70 weeks of age. N, A, and N*A indicate nutrition, age, and nutrition‐by‐age interaction effects, respectively. Superscripts indicate differences (P < 0.05): a,b, group differences within age; *, age differences within group. Bulls in the low nutrition group were older at puberty (321 days) than bulls in the medium and high nutrition groups (299 and 288 days, respectively), whereas bulls in the high nutrition group had greater paired‐testes weight at 70 weeks of age (655 g) than bulls in the low and medium nutrition groups (520 and 549 g).

Source: From [2], © 2007, Elsevier.

Figure 5.4 Mean (± SEM) number of LH pulses and serum testosterone concentrations in Angus and Angus × Charolais bulls receiving medium (control) or high nutrition from 10 to 30 weeks of age and the same medium nutrition from 31 to 74 weeks. N, A, and N*A indicate nutrition, age, and nutrition‐by‐age interaction effects, respectively. Superscript a and b indicate differences (P = 0.09) between groups within age. Bulls in the high nutrition group were younger at puberty (314 days) and had greater paired‐testes weight at 74 weeks of age (610 g) than bulls in the medium group (327 days and 531 g, respectively).

Source: From [3], © 2007, Elsevier.

Figure 5.5 Mean (± SEM) number of LH pulses and serum testosterone concentrations in Angus and Angus × Charolais bulls receiving medium (control) from 10 to 70 weeks of age or low nutrition from 10 to 26 weeks of age and either medium or high nutrition from 27 to 70 weeks of age. N, A, and N*A indicate nutrition, age, and nutrition‐by‐age interaction effects, respectively. Bulls in the medium/medium nutrition group were younger at puberty and had greater paired‐testes weight at 70 weeks of age than those in the low/medium nutrition group (293 vs 331 days and 600 vs 528 g, respectively). Age at puberty and paired‐testes weight for bulls in the low/high nutrition group were intermediate (313 days and 553 g, respectively).

Source: From [4], © 2007, Society for Reproduction and Fertility.

During the prepubertal period there is a progressive increase in the proportion of testicular parenchyma occupied by seminiferous tubules, and seminiferous tubule diameter increases to approximately 125 μm at six months of age [20, 36]. FSH‐binding sites can be observed in seminiferous tubules of bull calves at birth and at four months age, and decreased inhibin concentrations, coupled with increased FSH concentrations, stimulate the proliferation of undifferentiated Sertoli cells [6, 22]. Although there is considerable evidence that FSH is essential for normal Sertoli cell function, the period of Sertoli cell differentiation coincides with the initiation of testosterone secretion by the Leydig cells, indicating that testosterone may also be involved in promoting maturation of undifferentiated Sertoli cells. At approximately four months of age, undifferentiated Sertoli cells enter the G₀ phase of the cell cycle for the rest of the bull's life. With the end of the proliferative phase, undifferentiated Sertoli cells begin to transform into adult‐type Sertoli cells. Opposing cell membranes of adjacent undifferentiated Sertoli cells start to develop extended junctional complexes above the spermatogonia and in the basal portion of the tubules; “cracking” of the tubular cytoplasm is first detected around six months of age [1,15–17]. As immature Sertoli cells begin to differentiate they cease to secrete AMH and circulating concentrations of this hormone decrease after four months of age [1]. FSH secretion, maturation of Sertoli cells, and increased testosterone secretion are probably also involved in the differentiation of gonocytes into spermatogonia. Gonocytes are gradually displaced to a position close to the basal lamina and divide by mitosis, originating A‐spermatogonia. Differentiation and degeneration result in the complete disappearance of gonocytes from the seminiferous tubules by five months of age. A‐spermatogonia divide mitotically to form In‐spermatogonia and B‐spermatogonia, which in turn enter meiosis around four to five months of age [15, 17, 20, 36, 37].