Directory UMM :Data Elmu:jurnal:A:Animal Reproduction Science:Vol60-61.Issue1-4.Jul2000:
www.elsevier.comrlocateranireprosci
Efficiency of spermatogenesis:
a comparative approach
L. Johnson
a,c,), D.D. Varner
b, M.E. Roberts
a, T.L. Smith
a,
G.E. Keillor
a, W.L. Scrutchfield
b aDepartment of Veterinary Anatomy and Public Health, College of Veterinary Medicine, Texas A&M UniÕersity, College Station, TX 77843-4458, USA
b
Department of Large Animal Medicine and Surgery, College of Veterinary Medicine, Texas A&M UniÕersity,
College Station, TX 77843-4458, USA
c
Center for EnÕironmental and Rural Health, College of Veterinary Medicine, Texas A&M UniÕersity,
College Station, TX 77843-4458, USA
Abstract
Efficiency of spermatogenesis is the estimated number of spermatozoa produced per day per gram of testicular parenchyma. Spermatogenesis is the process of cell division and cell differentia-tion by which spermatozoa are produced in testes. Efficiency of spermatogenesis is influenced by species differences in the numerical density of germ cell nuclei and in the life span of these cells. Activities of spermatogonia, spermatocytes, and spermatids partition spermatogenesis into three
Ž .
major divisions spermatocytogenesis, meiosis, and spermiogenesis, respectively . Spermatocyto-genesis involves mitotic germ cell division to produce stem cells and primary spermatocytes. Meiosis involves duplication of chromosomes, exchange of genetic material, and two cell divisions that reduce the chromosome number and yield four spermatids. In spermiogenesis, spherical spermatids differentiate into mature spermatids which are released in the lumen of seminiferous tubules as spermatozoa. Spermatogenesis and germ cell degeneration can be quanti-fied from numbers of germ cells in various developmental steps throughout spermatogenesis. Germ cell degeneration occurs throughout spermatogenesis; however, the greatest impact occurs during spermatocytogenesis and meiosis. There are species and seasonal influences on the developmental steps in spermatogenesis at which germ cell degeneration occurs. Number of Sertoli cells, amount of smooth endoplasmic reticulum of Leydig cells, and the number of missing generations of germ cells within the spermatogenic stage of the cycle influence efficiency of spermatogenesis. Efficiency of spermatogenesis is influenced to the amount of germ cell
degenera-)Corresponding author. Tel.:q1-979-845-9279; fax:q1-979-847-8981.
Ž .
E-mail address: [email protected] L. Johnson .
0378-4320r00r$ - see front matterq2000 Published by Elsevier Science B.V. All rights reserved. Ž .
(2)
Published by Elsevier Science B.V. All rights reserved.
Keywords: Spermatogenesis; Species comparisons; Germ cell degeneration
1. Introduction
1.1. Definition and background
Spermatogenesis is the sum total of the events that occur within the testis that
Ž .
produce spermatozoa Johnson, 1991b . Spermatogenesis occurs within seminiferous tubules of the testis. It is a lengthy, chronological process by which stem cell spermatogonia divide by mitosis to maintain their own numbers and to cyclically produce primary spermatocytes that undergo meiosis to produce haploid spermatids
Ž .
which differentiate without further division into spermatozoa. The efficiency of spermatogenesis is the number of spermatozoa produced per gram of testicular parenchyma and is not influenced by difference in testicular size among animals.
Spermatocytogenesis, meiosis, and spermiogenesis are characterized by division andror differentiation of spermatogonia, spermatocytes, and spermatids, respectively,
Ž .
and are three major divisions of spermatogenesis Fig. 1 . In the bull, these divisions Ž
take 21, 23, and 17 days, respectively, for a total duration of 61 days Fig. 1; Amann, .
1970 . During spermatocytogenesis, stem cell spermatogonia divide by mitosis to Ž produce other stem cells that continue the lineage throughout the adult life of males Fig.
.
1 . Stem cells give rise to spermatogonia that cyclically produce committed spermatogo-nia which proliferate andror differentiate to produce primary spermatocytes that un-dergo meiosis. Meiosis allows exchange of genetic material between homologous
Ž chromosomes of primary spermatocytes and the production of haploid spermatids Fig.
. Ž .
1 . During spermiogenesis Fig. 1 , spermatids differentiate from cells with spherical nuclei into mature germ cells shaped like spermatozoa for that species. The flagellum is developed into a tail, and the head of the spermatozoon is composed of the compressed
Ž .
nucleus source of the male genome and an acrosome with its enzymes necessary to penetrate the layers of the egg.
1.2. Kinetics of spermatogenesis
Ž .
The spermatogenic cycle cycle of the seminiferous epithelium is superimposed on Ž
the major divisions of spermatogenesis spermatocytogenesis, meiosis, and spermiogene-.
sis; Fig. 1 . The cycle of the seminiferous epithelium is ‘‘a series of changes in a given
Ž .
area region of seminiferous epithelium between two appearances of the same
develop-Ž . Ž .
mental stages steps ’’ Leblond and Clermont, 1952 and lasts for 13.5 days in the bull. Ž
If spermiation release of spermatozoa from seminiferous epithelium and counterpart to .
ovulation in the female is used as a reference point, the spermatogenic cycle would be all the events that occur between two consecutive spermiations from a given region of the tubule.
(3)
Fig. 1. Drawings and classification of germ cells at different developmental steps in the three major divisions
Ž .
of spermatogenesis spermatocytogenesis, meiosis, and spermiogenesis combined to make the eight stages of
Ž .
the cycle of bull seminiferous epithelium. During the 21 days of spermatocytogenesis, A spermatogonia A
Ž . Ž .
enters cyclic at 13.5-day interval activity during stage III and undergo division to produce intermediate In ,
Ž . Ž .
B B spermatogonia, and leptotene primary spermatocytes L . During the 23 days of meiosis, leptotene
Ž . Ž . Ž .
primary spermatocytes differentiate through zygotene Z , pachytene P , and diplotene D before the first
Ž .
meiotic division to produce secondary spermatocytes SS , and the second meiotic division to produce Sa
Ž . Ž .
spermatids Sa . During the 17 days of spermiogenesis, Sa spermatids differentiate through Sb1 Sb , Sb1 2 ŽSb , Sc Sc , Sd2. Ž . 1ŽSd , and Sd1. 2ŽSd2.steps of development before spermiation as spermatozoa. The letters indicate the developmental step, and the numbers associated with each germ cell step indicate the developmen-tal age of each cell type in the middle of each spermatogenic stage. The cycle length is 13.5 days, and the
Ž .
duration of spermatogenesis is 61 days in the bull. Modified from Johnson et al. 1994 .
The cycle length and frequency at which spermatozoa are released both are deter-mined by the rate at which committed spermatogonia enter the process of
spermatogene-Ž
sis. The cycle length and duration of spermatogenesis from the production of committed
. Ž .
spermatogonia to spermiation are species-specific Swierstra et al, 1974; Amann, 1986 . The cycle length in days for the prairie vole is 7.2, hamster 8.7, mouse 8.9, rhesus monkey 9.5, rabbit 10.7, stallion 12.2, bull 13.5, beagle dog 13.6, and man 16 ŽClermont, 1963; Swierstra et al, 1974; Amann, 1981, 1986 ..
The stage represents an association of 4–5 germ cells, each of which is in a specific, chronological, developmental step in spermatogenesis. The assignment of stages repre-sent man-made divisions of naturally cyclically occurring cellular associations. In bulls,
(4)
. Ž . Desjardins, 1974 . Fourteen stages have been described in rats Clermont, 1972 , eight
Ž . Ž .
in the horse Swierstra et al, 1974 , and only six stages in humans Clermont, 1963 . The
Ž . Ž .
bull Amann, 1970 and horse Swierstra et al, 1974 , like most species, have mainly only one stage of the cycle represented in a cross-section of the seminiferous tubule.
Ž .
Humans have more than two stages per cross-section Clermont, 1963 . 1.3. Testis
Quantitative approaches have been extended to calculate daily sperm production, a quantitative measure of spermatogenesis to express the total number of spermatozoa
Ž
produced per day by a testis or paired testes Kennelly and Foote, 1964; Amann, 1970; .
Johnson, 1986b .
Considering the life span and theoretical yield of a specific germ cell, a daily expression of spermatozoan production can be obtained from the number of germ cells
Ž .
of that type in the testis Kennelly and Foote, 1964; Amann, 1970 . The life span of a germ cell is the duration of stages of the cycle in which that cell type occurs. Theoretical yields are calculated by 2n, where n is the number of cell divisions between that cell type and spermatids.
Daily sperm production per gram of testicular parenchyma is a measure of efficiency Ž
of spermatogenesis, and it is useful in species comparisons Fig. 2; Amann et al, 1976;
Fig. 2. Efficiency of spermatogenesis in various species based on potential daily sperm production per gram parenchyma at different developmental steps in spermatogenesis of the rat, bull, horse, boar, and human. Potential daily sperm production per gram is calculated from numbers of B spermatogonia, pachytene primary
Ž . Ž
spermatocytes, Golgi and cap phase spermatids round spermatids , and maturation-phase spermatids
elon-. Ž .
gated spermatids . Adult rats )400 g experienced no significant loss during these different steps in
Ž
spermatogenesis. Adult horses had early germ cell degeneration in spermatogenesis end of spermatocyte
.
formation with no subsequent losses. Younger adult humans had significant losses during the second meiotic division. Humans and bulls have much lower efficiency of spermatogenesis than do other species. Boars and humans have significant losses in potential production at the end of meiosis. Bulls and horses have no
Ž . Ž .
significant losses at the end of meiosis. Modified from Johnson et al. 1981, 1984a,b, 1994 , Johnson 1986b ,
Ž .
(5)
. Ž 6 .
Johnson, 1986b . Humans have a much lower efficiency 4–6=10 rg of
spermatogen-Ž .
esis Johnson et al., 1981 than do other species tested, including rhesus monkeys
Ž 6 . Ž 6 . Ž 6 . Ž 6 .
23=10 rg , rabbits 25=10 rg , rats 20–24=10 rg boars 23=10 rg ,
stal-Ž 6 . Ž 6 . Ž 6 .
lions 16–19=10 rg , rams 21=10 rg , hamsters 24=10 rg , and even bulls Ž12=106rg. ŽAmann et al, 1976; Amann, 1981; Johnson, 1986b . Comparisons of.
daily sperm production per gram parenchyma vs. potential daily sperm production based on germ cells in different developmental steps of spermatogenesis facilitate detection of
Ž species differences in sites of germ cell degeneration in spermatogenesis Fig. 2;
. Johnson et al, 1999a,b .
Ž .
Lower efficiency of spermatogenesis in human testes compared to other species
Ž . Ž
results from a longer duration of spermatogenesis 74 days , longer cycle length 16
. Ž . Ž
days Clermont, 1972 , and lower density of germ cells in human testes Johnson,
. 6
1986b . In humans, the number of round spermatids per gram parenchyma is 49.2=10 ŽJohnson, 1986a,b . In comparison, in the rat, whose cycle length is 12.9 days, and the. horse whose cycle is 12.2 days, the number of round spermatids per gram is 190=106
Ž . 6 Ž .
Johnson et al, 1984a and 162=10 , respectively Johnson, 1985 . The percentages of the human testis occupied by seminiferous tubules and seminiferous epithelium are
Ž .
lower than that for bulls, horses, or rats Fig. 3; Johnson, 1986b . The reason humans differ from other species in their lower testicular germ cell density and longer cycle length remains a mystery. However, it does not appear to be a problem for the survival of the human species, considering the population explosion on the earth.
Germ cell degeneration at specific developmental steps of spermatogenesis has been quantified by comparing daily sperm production per gram parenchyma based on germ
Ž .
cell types in different steps of development Fig. 2; Johnson, 1986b . This has been done
Ž . Ž . Ž .
in the boar Kennelly and Foote, 1964 , bull, Amann, 1970 , rat Johnson et al, 1984a ,
Ž . Ž .
horse Johnson, 1985 , and human Johnson, 1986b . However, among breeds of boars, the efficiency of spermatogenesis and potential daily sperm production based on germ
Ž .
Fig. 3. Composition of testes in various species expressed as the percentage volume density of the testicular parenchyma occupied by seminiferous tubules or seminiferous epithelium. In the human, the volume density of
Ž .
seminiferous epithelium is less than 50% of the testicular parenchyma. Modified from Johnson 1986b and
Ž .
(6)
degenerative rates throughout spermatogenesis.
For species comparisons, daily sperm production has been estimated at different
Ž .
development steps throughout spermatogenesis Fig. 2 . While humans and boars experienced a 30–40% reduction in potential sperm production during the end of meiosis, there was no comparable loss or degeneration during meiosis of the bull or stallion. In the breeding season of the stallion, there was a larger number of A spermatogonia than whose progeny could be sustained. This resulted in significant
Ž .
degeneration of B spermatogonia at the end of meiosis Johnson, 1985 . In the bull, a significant number of degenerated germ cells have been noted during
spermatocytogene-Ž .
sis Berndtson and Desjardins, 1974 . Another way to evaluate degeneration of germ cells at different developmental steps is by the ratio of more advanced germ cell per type A spermatogonium.
1.4. Season
Ž .
Stallions unlike bulls, boars, rats, and humans modulate or regulate daily sperm production with season while continuing to produce spermatozoa throughout the year. Germ cell degeneration during meiosis and seasonal modulation of the number of A
w
spermatogonia which is twice as large in the breeding season as in the non-breeding
Ž .x
season of the horse testis Johnson, 1986b are mechanisms that seasonally regulate spermatogenesis. The number of A plus B spermatogonia per testis in the breeding1
Ž 9. Ž .
season 5.1"0.2=10 was 71% higher p-0.01 than the number in the
non-breed-Ž 9. Ž .
ing season 3.0"0.3=10 . Daily sperm production per testis was 84% p-0.01 higher in the breeding season. Season affects the number of different subtypes of
Ž .
spermatogonia per testis Fig. 11 .
Seasonal modulation of A spermatogonia in a species may result from proliferation of renewing stem cells. The reserve stem cell spermatogonium is the youngest form of
Ž
germ cells which may be dormant in testes active in spermatogenesis Ao stem cell; .
Clermont, 1972 or actively involved in producing other stem cells or proliferating
Ž .
spermatogonia As stem cells; Huckins, 1971 . These cells carry on the lineage throughout the life of adult males. Seasonal variation in the number of renewing stem cells has been found in other seasonal breeders such as rams and red deer stags ŽHochereau-de Reviers, 1981 . In the horse, the number of the most primitive spermato-.
Ž . Ž . Ž .
gonia A1 was 25% greater p-0.05 in the breeding season Fig. 4 . Hence, seasonal differences in number of more primitive spermatogonia contribute significantly to seasonal differences in total number of spermatogonia in the horse.
Season influences the developmental steps or spermatogonial subtypes that degener-Ž ate. The yield of B2rA or B1 2rA was greater in the breeding season of the horse Fig.2
.
4; Johnson, 1991a . However, the yield of conversions of B2 spermatogonia to early primary spermatocytes was greater in the non-breeding season. The greater degeneration of B2 spermatogonia in the breeding season results form an overpopulation of A spermatogonia beyond the increased number of Sertoli cells in the breeding season.
Ž .
Researchers Johnson, 1985, 1986a found a positive relationship between the number of A1 spermatogonia and the amount of degeneration that occurred in A2 and A3
(7)
Fig. 4. Number and yield of spermatogonia in adult equine testes in the breeding and nonbreeding seasons. The
Ž .
number of horse A , A , A , B , and B spermatogonia A , A , A B , and B , respectively per testis and1 2 3 1 2 1 2 3 1 2
the yield of specific spermatogonial subtypes to B2 spermatogonia are different between the breeding or
Ž . Ž .
non-breeding seasons. a The number of A spermatogonia is 25% p1 -0.05 greater in the breeding season of the horse. The numbers of A , A , B , and B2 3 1 2 spermatogonia and preleptotenerleptotenerzygotene
Ž . Ž .
primary spermatocytes PS are 39%, 83%, 91%, 110%, and 49% greater p-0.01 , respectively, in the
Ž . Ž .
breeding season. b Although the conversions of A to B and A to B spermatogonia are similar p3 2 1 2 )0.05
Ž .
between seasons, the conversions of A to B and A to B are greater p1 2 2 2 -0.01 in the breeding season. The
Ž . Ž
conversion of B to early primary spermatocytes is less p2 -0.01 in the breeding season from Johnson et al.,
.
1991 .
spermatogonia. As the result of a higher yield of early spermatogonial subtypes in the breeding season, the number of late spermatogonial subtypes was significantly increased ŽFig. 4 . This increased yield early in spermatogenesis appeared to make the greatest. contribution to the significantly increased spermatogonial numbers in the breeding season. Although not seasonal, the bull had a significant loss of potential daily sperm
Ž .
production regulatory degeneration or trimming of spermatogonial progeny between
Ž .
spermatocytogenesis and meiosis Fig. 2 .
Fig. 5. Effect of season on the number of Sertoli cells in the equine testis as viewed at different times of the year. Number of Sertoli cells found in 43–48 adult horses during each 3-month period throughout 1 complete
Ž . Ž
year illustrates more p-0.05 Sertoli cells per gram parenchyma in May–July the natural breeding season
.
of the horse than in other periods. The number of Sertoli cells per testis is greater in May–July compared with
Ž .
the value in August–October or February–April p-0.05 or compared with the value for November–January
(8)
Ž .
Fig. 6. Species comparison in the number of Sertoli cells and in the germ cell:Sertoli cell ratio. a The number
Ž .
of Sertoli cells per gram parenchyma or per testis for the rat, bull, boar, horse, and human, and b the number of germ cells per Sertoli cell. The bull and human have fewer germ cells supported by each Sertoli cell than
Ž .
does the rat, horse, or boar from Johnson, 1986b; Johnson et al., 1994, 1996b; Okwun et al., 1996 .
Stereological methods of histologic images have illustrated seasonal variation in Ž
number of Sertoli cells and the germ cell:Sertoli cell ratio in the horse Figs. 5 and 6;
. Ž
Johnson, 1986a . Seasonal variation in number of Sertoli cells Johnson and Thompson, .
1983; Johnson, 1986a have characterized the annual cycle of the Sertoli cell population
Ž . Ž
in the horse Fig. 5 . There is significantly more Sertoli cells in the summer natural
. Ž .
breeding season , and there is a dose month effect based on the time of the year the
Ž .
samples were taken Fig. 5 . The ratio of spermatogonia, spermatids, or all germ cells in
Ž .
stage VIII tubules was greater in the breeding season of the horse Johnson, 1986a . Hence, Sertoli cell function appears to be enhanced during the breeding season with seasonal modulation of spermatogenesis in the horse.
2. Germ cell degeneration 2.1. General considerations
Degeneration of germ cell occurs largely during spermatocytogenesis and meiosis ŽJohnson, 1986b . Losses during spermatocytogenesis include 25% in mice, 11% in. Sherman rats, and 75% in adult Sprague–Dawley rats. Greater degeneration of
sper-Ž .
matogonia in rams occurs following long day illumination Johnson, 1986b . Degenera-tion of B spermatogonia in horses is greater in the breeding season when the number of
Ž .
A spermatogonia is doubled Fig. 4; Johnson, 1985 . Meiotic divisions account for a 13% loss of potential production in mice, 2% in Sprague–Dawley rats, 27% in Sherman
Ž
rats, 25% in rabbits, and 6–15% in stallions depending upon season Johnson, 1985,
. Ž .
1986b . In rams, fewer 40–50% spermatids were found after long day illumination ŽJohnson, 1986b, 1991b ..
Germ cell degeneration during spermiogenesis was noted in Sherman rats and mice.
Ž . Ž .
A loss of 6% or less depending on season occurred in horses Johnson, 1985 . Bulls ŽAmann, 1970 and adult Sprague–Dawley rats. Ž)400 g had no significant germ cell.
Ž .
(9)
No significant degeneration of human germ cells occurred between type B
spermato-Ž .
gonia and secondary spermatocytes or during spermiogenesis Fig. 2; Johnson, 1986b . A 30–40% loss from germ cell degeneration occurred during the meiotic divisions in humans. The loss of spermatozoan production late in meiosis is significantly, negatively
Ž .
correlated rs y0.86 with daily sperm production per gram parenchyma in humans. Likewise, serum concentrations of FSH in men are positively correlated with the percentage of germ cell degeneration during post prophase of meiosis. Degeneration
Ž detected late in meiosis occurred during the second meiotic division in young men Fig.
.
2 and is greater in aged men. It is not known why humans have a greater degeneration
Ž .
rate late in meiosis than other species Fig. 2 , but it appears to be a critical step in human spermatogenesis that could be exploited to increase efficiency of spermatogene-sis or to devise contraceptive strategies. There was no similar loss during meiospermatogene-sis in bulls, horses, or rats, but boars have a significant loss of potential for sperm production
Ž .
during post prophase of meiosis Fig. 2 .
3. Conclusions
Spermatogenesis is a long but orderly process by which spermatozoa are produced in seminiferous tubules and is divided into spermatocytogenesis, meiosis, and spermiogen-esis.
Germ cell degeneration occurs throughout spermatocytogenesis, but is greater during spermatocytogenesis and meiosis and can vary with pubertal development, age, and species.
Bulls have a lower efficiency of spermatogenesis than most species including rats and horses examined, but higher than that of humans.
Sertoli cell number is important in determining daily sperm production in bulls and boars as well as in other species including rats, horses, and humans.
Acknowledgements
The authors would like to thank Vince B. Hardy and Rebecca S. Heck for their excellent technical assistance and Penny Churchill for expert secretarial assistance with the manuscript. This work is funded in part by Link Estate Equine Endowment and NIH Funding K04AG00465, N01HD-83281, P30E09196, and T32G507273.
References
Ž .
Amann, R.P., 1970. Sperm production rates. In: Johnson, A.D., Gomes, W.R., VanDemark, N.L. Eds. , The Testis Vol. 1 Academic Press, New York, pp. 433–482.
Amann, R.P., 1981. A critical review of methods for evaluation of spermatogenesis from seminal character-istics. J. Androl. 2, 37–58.
Amann, R.P., 1986. Detection of alterations in testicular and epididymal function in laboratory animals. Environ. Health Perspect. 70, 149–158.
(10)
epididymal spermatozoal reserves and transit time of spermatozoa through the epididymis of the Rhesus monkey. Biol. Reprod. 15, 586–592.
Berndtson, W.E., Desjardins, C., 1974. The cycle of the seminiferous epithelium and spermatogenesis in the bovine testis. Am. J. Anat. 140, 167–180.
Clermont, Y., 1963. The cycle of the seminiferous epithelium in man. Am. J. Anat. 112, 35–51.
Clermont, Y., 1972. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogo-nial renewal. Physiol. Rev. 52, 198–236.
Ž .
Hochereau-de Reviers, M.T., 1981. Control of spermatogonial multiplication. In: McKerns, K.W. Ed. , Reproductive Processes and Contraception. Plenum Press, New York, pp. 307–331.
Huckins, C., 1971. The spermatogonial stem cell population in adult rats: I. Their morphology, proliferation, and maturation. Anat. Rec. 169, 533–558.
Johnson, L., 1985. Increased daily sperm production in the breeding season of stallions is explained by an elevated population of spermatogonia. Biol. Reprod. 32, 1181–1190.
Johnson, L., 1986a. A new approach to quantification of Sertoli cells that avoids problems associated with the irregular nuclear surface. Anat. Rec. 214, 231–237.
Johnson, L., 1986b. Review article: spermatogenesis and aging in the human. J. Androl. 7, 331–354. Johnson, L., 1991a. Seasonal differences in equine spermatocytogenesis. Biol. Reprod. 44, 284–291.
Ž .
Johnson, L., 1991b. Spermatogenesis. In: Cupps, P.T. Ed. , Reproduction in Domestic Animals. 4th edn. Academic Press, New York, pp. 173–219.
Johnson, L., Nguyen, H.B., 1983. Annual cycle of the Sertoli cell population in adult stallions. J. Reprod. Fertil. 76, 311–316.
Johnson, L., Thompson, D.L. Jr., 1983. Age-related and seasonal variation in the Sertoli cell population, daily sperm production and serum concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone in stallions. Biol. Reprod. 29, 777–789.
Johnson, L., Petty, C.S., Neaves, W.B., 1981. A new approach to quantification of spermatogenesis and its application to germinal cell attrition during human spermiogenesis. Biol. Reprod. 25, 217–226.
Johnson, L., Lebovitz, R.M., Samson, W.K., 1984a. Germ cell degeneration in normal and microwave-irradia-ted rats: potential sperm production rates at different developmental steps in spermatogenesis. Anat. Rec. 209, 501–507.
Johnson, L., Petty, C.S., Porter, J.C., Neaves, W.B., 1984b. Germ cell degeneration during postprophase of meiosis and serum concentrations of gonadotropins in young adult and older adult men. Biol. Reprod. 31, 779–784.
Johnson, L., Varner, D.D., Tatum, M.E., Scrutchfield, W.L., 1991. Season but not age affects Sertoli cell number in adult stallions. Biol. Reprod. 45, 404–410.
Johnson, L., Wilker, C.E., Cerelli, J.S., 1994. Spermatogenesis in the bull. Tech. Conf. Artif. Insem. Reprod. 15, 9–27.
Johnson, L., Falk, G.U., Spoede, G.E., 1999a. Male reproductive system, nonhuman mammals. In: 1st edn.
Ž .
Knobnil, E., Neill, J.D. Eds. , Encyclopedia of Reproduction Vol. 3 Academic Press, San Diego, pp. 49–60.
Johnson, L., McGowen, T.A., Keillor, G.E., 1999b. Testis, overview. In: 1st edn. Knobnil, E., Neill, J.D.
ŽEds. , Encyclopedia of Reproduction Vol. 4 Academic Press, San Diego, pp. 769–784..
Kennelly, J.J., Foote, R.H., 1964. Sampling boar testes to study spermatogenesis quantitatively and to predict sperm production. J. Anim. Sci. 23, 160–167.
Leblond, C.P., Clermont, Y., 1952. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann. N. Y. Acad. Sci. 55, 548–573.
Okwun, O.E., Igboeli, G., Ford, J.J., Lunstra, D.D., Johnson, L., 1996. Number and function of Sertoli cells, number and yield of spermatogonia, and daily sperm production in three breeds of boar. J. Reprod. Fertil. 107, 137–149.
Swierstra, E.E., Gebauer, M.R., Pickett, B.W., 1974. Reproductive physiology of the stallion: I. Spermatogen-esis and testis composition. J. Reprod. Fertil. 40, 113–123.
(1)
. Ž 6 .
Johnson, 1986b . Humans have a much lower efficiency 4–6=10 rg of
spermatogen-Ž .
esis Johnson et al., 1981 than do other species tested, including rhesus monkeys
Ž 6 . Ž 6 . Ž 6 . Ž 6 .
23=10 rg , rabbits 25=10 rg , rats 20–24=10 rg boars 23=10 rg ,
stal-Ž 6 . Ž 6 . Ž 6 .
lions 16–19=10 rg , rams 21=10 rg , hamsters 24=10 rg , and even bulls
Ž12=106 . Ž .
rg Amann et al, 1976; Amann, 1981; Johnson, 1986b . Comparisons of
daily sperm production per gram parenchyma vs. potential daily sperm production based on germ cells in different developmental steps of spermatogenesis facilitate detection of
Ž
species differences in sites of germ cell degeneration in spermatogenesis Fig. 2;
.
Johnson et al, 1999a,b .
Ž .
Lower efficiency of spermatogenesis in human testes compared to other species
Ž . Ž
results from a longer duration of spermatogenesis 74 days , longer cycle length 16
. Ž . Ž
days Clermont, 1972 , and lower density of germ cells in human testes Johnson,
. 6
1986b . In humans, the number of round spermatids per gram parenchyma is 49.2=10
ŽJohnson, 1986a,b . In comparison, in the rat, whose cycle length is 12.9 days, and the.
horse whose cycle is 12.2 days, the number of round spermatids per gram is 190=106
Ž . 6 Ž .
Johnson et al, 1984a and 162=10 , respectively Johnson, 1985 . The percentages of
the human testis occupied by seminiferous tubules and seminiferous epithelium are
Ž .
lower than that for bulls, horses, or rats Fig. 3; Johnson, 1986b . The reason humans differ from other species in their lower testicular germ cell density and longer cycle length remains a mystery. However, it does not appear to be a problem for the survival of the human species, considering the population explosion on the earth.
Germ cell degeneration at specific developmental steps of spermatogenesis has been quantified by comparing daily sperm production per gram parenchyma based on germ
Ž .
cell types in different steps of development Fig. 2; Johnson, 1986b . This has been done
Ž . Ž . Ž .
in the boar Kennelly and Foote, 1964 , bull, Amann, 1970 , rat Johnson et al, 1984a ,
Ž . Ž .
horse Johnson, 1985 , and human Johnson, 1986b . However, among breeds of boars, the efficiency of spermatogenesis and potential daily sperm production based on germ
Ž .
Fig. 3. Composition of testes in various species expressed as the percentage volume density of the testicular parenchyma occupied by seminiferous tubules or seminiferous epithelium. In the human, the volume density of
Ž .
seminiferous epithelium is less than 50% of the testicular parenchyma. Modified from Johnson 1986b and
Ž .
(2)
significant number of degenerated germ cells have been noted during
spermatocytogene-Ž .
sis Berndtson and Desjardins, 1974 . Another way to evaluate degeneration of germ cells at different developmental steps is by the ratio of more advanced germ cell per type A spermatogonium.
1.4. Season
Ž .
Stallions unlike bulls, boars, rats, and humans modulate or regulate daily sperm production with season while continuing to produce spermatozoa throughout the year. Germ cell degeneration during meiosis and seasonal modulation of the number of A
w
spermatogonia which is twice as large in the breeding season as in the non-breeding
Ž .x
season of the horse testis Johnson, 1986b are mechanisms that seasonally regulate
spermatogenesis. The number of A plus B spermatogonia per testis in the breeding1
Ž 9. Ž .
season 5.1"0.2=10 was 71% higher p-0.01 than the number in the
non-breed-Ž 9. Ž .
ing season 3.0"0.3=10 . Daily sperm production per testis was 84% p-0.01
higher in the breeding season. Season affects the number of different subtypes of
Ž .
spermatogonia per testis Fig. 11 .
Seasonal modulation of A spermatogonia in a species may result from proliferation of renewing stem cells. The reserve stem cell spermatogonium is the youngest form of
Ž
germ cells which may be dormant in testes active in spermatogenesis Ao stem cell;
.
Clermont, 1972 or actively involved in producing other stem cells or proliferating
Ž .
spermatogonia As stem cells; Huckins, 1971 . These cells carry on the lineage
throughout the life of adult males. Seasonal variation in the number of renewing stem cells has been found in other seasonal breeders such as rams and red deer stags
ŽHochereau-de Reviers, 1981 . In the horse, the number of the most primitive spermato-.
Ž . Ž . Ž .
gonia A1 was 25% greater p-0.05 in the breeding season Fig. 4 . Hence, seasonal
differences in number of more primitive spermatogonia contribute significantly to seasonal differences in total number of spermatogonia in the horse.
Season influences the developmental steps or spermatogonial subtypes that
degener-Ž
ate. The yield of B2rA or B1 2rA was greater in the breeding season of the horse Fig.2
.
4; Johnson, 1991a . However, the yield of conversions of B2 spermatogonia to early
primary spermatocytes was greater in the non-breeding season. The greater degeneration
of B2 spermatogonia in the breeding season results form an overpopulation of A
spermatogonia beyond the increased number of Sertoli cells in the breeding season.
Ž .
Researchers Johnson, 1985, 1986a found a positive relationship between the number of
(3)
Fig. 4. Number and yield of spermatogonia in adult equine testes in the breeding and nonbreeding seasons. The
Ž .
number of horse A , A , A , B , and B spermatogonia A , A , A B , and B , respectively per testis and1 2 3 1 2 1 2 3 1 2
the yield of specific spermatogonial subtypes to B2 spermatogonia are different between the breeding or
Ž . Ž .
non-breeding seasons. a The number of A spermatogonia is 25% p1 -0.05 greater in the breeding season of the horse. The numbers of A , A , B , and B2 3 1 2 spermatogonia and preleptotenerleptotenerzygotene
Ž . Ž .
primary spermatocytes PS are 39%, 83%, 91%, 110%, and 49% greater p-0.01 , respectively, in the
Ž . Ž .
breeding season. b Although the conversions of A to B and A to B spermatogonia are similar p3 2 1 2 )0.05
Ž .
between seasons, the conversions of A to B and A to B are greater p1 2 2 2 -0.01 in the breeding season. The
Ž . Ž
conversion of B to early primary spermatocytes is less p2 -0.01 in the breeding season from Johnson et al.,
.
1991 .
spermatogonia. As the result of a higher yield of early spermatogonial subtypes in the breeding season, the number of late spermatogonial subtypes was significantly increased
ŽFig. 4 . This increased yield early in spermatogenesis appeared to make the greatest.
contribution to the significantly increased spermatogonial numbers in the breeding season. Although not seasonal, the bull had a significant loss of potential daily sperm
Ž .
production regulatory degeneration or trimming of spermatogonial progeny between
Ž .
spermatocytogenesis and meiosis Fig. 2 .
Fig. 5. Effect of season on the number of Sertoli cells in the equine testis as viewed at different times of the year. Number of Sertoli cells found in 43–48 adult horses during each 3-month period throughout 1 complete
Ž . Ž
year illustrates more p-0.05 Sertoli cells per gram parenchyma in May–July the natural breeding season
.
of the horse than in other periods. The number of Sertoli cells per testis is greater in May–July compared with
Ž .
the value in August–October or February–April p-0.05 or compared with the value for November–January
(4)
Ž .
Fig. 6. Species comparison in the number of Sertoli cells and in the germ cell:Sertoli cell ratio. a The number
Ž .
of Sertoli cells per gram parenchyma or per testis for the rat, bull, boar, horse, and human, and b the number of germ cells per Sertoli cell. The bull and human have fewer germ cells supported by each Sertoli cell than
Ž .
does the rat, horse, or boar from Johnson, 1986b; Johnson et al., 1994, 1996b; Okwun et al., 1996 .
Stereological methods of histologic images have illustrated seasonal variation in
Ž
number of Sertoli cells and the germ cell:Sertoli cell ratio in the horse Figs. 5 and 6;
. Ž
Johnson, 1986a . Seasonal variation in number of Sertoli cells Johnson and Thompson,
.
1983; Johnson, 1986a have characterized the annual cycle of the Sertoli cell population
Ž . Ž
in the horse Fig. 5 . There is significantly more Sertoli cells in the summer natural
. Ž .
breeding season , and there is a dose month effect based on the time of the year the
Ž .
samples were taken Fig. 5 . The ratio of spermatogonia, spermatids, or all germ cells in
Ž .
stage VIII tubules was greater in the breeding season of the horse Johnson, 1986a . Hence, Sertoli cell function appears to be enhanced during the breeding season with seasonal modulation of spermatogenesis in the horse.
2. Germ cell degeneration
2.1. General considerations
Degeneration of germ cell occurs largely during spermatocytogenesis and meiosis
ŽJohnson, 1986b . Losses during spermatocytogenesis include 25% in mice, 11% in.
Sherman rats, and 75% in adult Sprague–Dawley rats. Greater degeneration of
sper-Ž .
matogonia in rams occurs following long day illumination Johnson, 1986b . Degenera-tion of B spermatogonia in horses is greater in the breeding season when the number of
Ž .
A spermatogonia is doubled Fig. 4; Johnson, 1985 . Meiotic divisions account for a 13% loss of potential production in mice, 2% in Sprague–Dawley rats, 27% in Sherman
Ž
rats, 25% in rabbits, and 6–15% in stallions depending upon season Johnson, 1985,
. Ž .
1986b . In rams, fewer 40–50% spermatids were found after long day illumination
ŽJohnson, 1986b, 1991b ..
Germ cell degeneration during spermiogenesis was noted in Sherman rats and mice.
Ž . Ž .
A loss of 6% or less depending on season occurred in horses Johnson, 1985 . Bulls
ŽAmann, 1970 and adult Sprague–Dawley rats. Ž)400 g had no significant germ cell.
Ž .
(5)
No significant degeneration of human germ cells occurred between type B
spermato-Ž .
gonia and secondary spermatocytes or during spermiogenesis Fig. 2; Johnson, 1986b . A 30–40% loss from germ cell degeneration occurred during the meiotic divisions in humans. The loss of spermatozoan production late in meiosis is significantly, negatively
Ž .
correlated rs y0.86 with daily sperm production per gram parenchyma in humans.
Likewise, serum concentrations of FSH in men are positively correlated with the percentage of germ cell degeneration during post prophase of meiosis. Degeneration
Ž
detected late in meiosis occurred during the second meiotic division in young men Fig.
.
2 and is greater in aged men. It is not known why humans have a greater degeneration
Ž .
rate late in meiosis than other species Fig. 2 , but it appears to be a critical step in human spermatogenesis that could be exploited to increase efficiency of spermatogene-sis or to devise contraceptive strategies. There was no similar loss during meiospermatogene-sis in bulls, horses, or rats, but boars have a significant loss of potential for sperm production
Ž .
during post prophase of meiosis Fig. 2 .
3. Conclusions
Spermatogenesis is a long but orderly process by which spermatozoa are produced in seminiferous tubules and is divided into spermatocytogenesis, meiosis, and spermiogen-esis.
Germ cell degeneration occurs throughout spermatocytogenesis, but is greater during spermatocytogenesis and meiosis and can vary with pubertal development, age, and species.
Bulls have a lower efficiency of spermatogenesis than most species including rats and horses examined, but higher than that of humans.
Sertoli cell number is important in determining daily sperm production in bulls and boars as well as in other species including rats, horses, and humans.
Acknowledgements
The authors would like to thank Vince B. Hardy and Rebecca S. Heck for their excellent technical assistance and Penny Churchill for expert secretarial assistance with the manuscript. This work is funded in part by Link Estate Equine Endowment and NIH Funding K04AG00465, N01HD-83281, P30E09196, and T32G507273.
References
Ž .
Amann, R.P., 1970. Sperm production rates. In: Johnson, A.D., Gomes, W.R., VanDemark, N.L. Eds. , The Testis Vol. 1 Academic Press, New York, pp. 433–482.
Amann, R.P., 1981. A critical review of methods for evaluation of spermatogenesis from seminal character-istics. J. Androl. 2, 37–58.
Amann, R.P., 1986. Detection of alterations in testicular and epididymal function in laboratory animals. Environ. Health Perspect. 70, 149–158.
(6)
and maturation. Anat. Rec. 169, 533–558.
Johnson, L., 1985. Increased daily sperm production in the breeding season of stallions is explained by an elevated population of spermatogonia. Biol. Reprod. 32, 1181–1190.
Johnson, L., 1986a. A new approach to quantification of Sertoli cells that avoids problems associated with the irregular nuclear surface. Anat. Rec. 214, 231–237.
Johnson, L., 1986b. Review article: spermatogenesis and aging in the human. J. Androl. 7, 331–354. Johnson, L., 1991a. Seasonal differences in equine spermatocytogenesis. Biol. Reprod. 44, 284–291.
Ž .
Johnson, L., 1991b. Spermatogenesis. In: Cupps, P.T. Ed. , Reproduction in Domestic Animals. 4th edn. Academic Press, New York, pp. 173–219.
Johnson, L., Nguyen, H.B., 1983. Annual cycle of the Sertoli cell population in adult stallions. J. Reprod. Fertil. 76, 311–316.
Johnson, L., Thompson, D.L. Jr., 1983. Age-related and seasonal variation in the Sertoli cell population, daily sperm production and serum concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone in stallions. Biol. Reprod. 29, 777–789.
Johnson, L., Petty, C.S., Neaves, W.B., 1981. A new approach to quantification of spermatogenesis and its application to germinal cell attrition during human spermiogenesis. Biol. Reprod. 25, 217–226.
Johnson, L., Lebovitz, R.M., Samson, W.K., 1984a. Germ cell degeneration in normal and microwave-irradia-ted rats: potential sperm production rates at different developmental steps in spermatogenesis. Anat. Rec. 209, 501–507.
Johnson, L., Petty, C.S., Porter, J.C., Neaves, W.B., 1984b. Germ cell degeneration during postprophase of meiosis and serum concentrations of gonadotropins in young adult and older adult men. Biol. Reprod. 31, 779–784.
Johnson, L., Varner, D.D., Tatum, M.E., Scrutchfield, W.L., 1991. Season but not age affects Sertoli cell number in adult stallions. Biol. Reprod. 45, 404–410.
Johnson, L., Wilker, C.E., Cerelli, J.S., 1994. Spermatogenesis in the bull. Tech. Conf. Artif. Insem. Reprod. 15, 9–27.
Johnson, L., Falk, G.U., Spoede, G.E., 1999a. Male reproductive system, nonhuman mammals. In: 1st edn.
Ž .
Knobnil, E., Neill, J.D. Eds. , Encyclopedia of Reproduction Vol. 3 Academic Press, San Diego, pp. 49–60.
Johnson, L., McGowen, T.A., Keillor, G.E., 1999b. Testis, overview. In: 1st edn. Knobnil, E., Neill, J.D.
ŽEds. , Encyclopedia of Reproduction Vol. 4 Academic Press, San Diego, pp. 769–784..
Kennelly, J.J., Foote, R.H., 1964. Sampling boar testes to study spermatogenesis quantitatively and to predict sperm production. J. Anim. Sci. 23, 160–167.
Leblond, C.P., Clermont, Y., 1952. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann. N. Y. Acad. Sci. 55, 548–573.
Okwun, O.E., Igboeli, G., Ford, J.J., Lunstra, D.D., Johnson, L., 1996. Number and function of Sertoli cells, number and yield of spermatogonia, and daily sperm production in three breeds of boar. J. Reprod. Fertil. 107, 137–149.
Swierstra, E.E., Gebauer, M.R., Pickett, B.W., 1974. Reproductive physiology of the stallion: I. Spermatogen-esis and testis composition. J. Reprod. Fertil. 40, 113–123.