Depletion of the Spermatogonia from the Seminiferous Epithelium of the Rhesus Monkey after X Irradiation

Alphen, M. M. A. van; Kant, H. J. G. van de; Rooij, Dirk G. de

doi:10.2307/3577244

Cited by 109 publications

(61 citation statements)

References 18 publications

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“…From the highly variable EXOSC10 staining patterns of human spermatogonia, it may be hypothesised that the protein is redistributed between chromatin rarefaction zones and nucleoli, possibly accompanying transformation of one spermatogonial subtype into another. In this context, it seems of interest that Ad spermatogonia can transform into Ap spermatogonia when Ap spermatogonia are diminished, and only after this transition they will start to proliferate (van Alphen & de Rooij 1986). Also, the co-expression of EXOSC10 in chromatin rarefaction zones and nucleoli is suggestive of a functional relationship between these compartments as proposed earlier (compare Paniagua et al (1986)).…”

Section: Discussionmentioning

confidence: 88%

Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia

Kopylow¹,

Staege²,

Spiess³

et al. 2012

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It is unclear whether the distinct nuclear morphologies of human A dark (Ad) and A pale (Ap) spermatogonia are manifestations of different stages of germ cell development or phases of the mitotic cycle, or whether they may reflect still unknown molecular differences. According to the classical description by Clermont, human dark type A spermatogonium (Ad) may contain one, sometimes two or three nuclear 'vacuolar spaces' representing chromatin rarefaction zones. These structures were readily discerned in paraffin sections of human testis tissue during immunohistochemical and immunofluorescence analyses and thus represented robust morphological markers for our study. While a majority of the marker proteins tested did not discriminate between spermatogonia with and without chromatin rarefaction zones, doublesex-and mab-3-related transcription factor (DMRT1), tyrosine kinase receptor c-Kit/CD117 (KIT) and proliferation-associated antigen Ki-67 (KI-67) appeared to be restricted to subtypes which lacked the rarefaction zones. Conversely, exosome component 10 (EXOSC10) was found to accumulate within the rarefaction zones, which points to a possible role of this nuclear domain in RNA processing.

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Section: Discussionmentioning

confidence: 88%

Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia

Kopylow¹,

Staege²,

Spiess³

et al. 2012

Reproduction

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“…Various studies have suggested that Ap spermatogonia can undergo a transition, probably without division, into Ad spermatogonia (24,28,29). Because Ad spermatogonia are not proliferative, the transition of Ap into Ad may be a means of inactivating a certain proportion of the spermatogonial population (28,29). Moreover, studies in irradiated monkeys suggest that Ad spermatogonia may be able to undergo a transition back to Ap spermatogonia, thus allowing repopulation of the testis (28,29), further suggesting that Ad spermatogonia are reserve stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, Ap spermatogonia are probably the stem cells of the testis that renew their own population as well as produce cells committed to differentiation. Various studies have suggested that Ap spermatogonia can undergo a transition, probably without division, into Ad spermatogonia (24,28,29). Because Ad spermatogonia are not proliferative, the transition of Ap into Ad may be a means of inactivating a certain proportion of the spermatogonial population (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…Type Ap spermatogonia divide in the later stages of the spermatogenic cycle, to produce type B spermatogonia, as well as to renew their own population (21,22,24,25,28,29). Ad spermatogonia, however, rarely divide and are thus considered to be resting or reserve stem cells (21,22,24,25,28,29). Ap spermatogonia have been suggested to be the true stem cells of the testis, because Ap (and not Ad) spermatogonia are seen in humans after radiation therapy (30), after long-term estrogen therapy, and in the postpubertal cryptorchid testes (31).…”

Section: Discussionmentioning

confidence: 99%

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Impairment of Spermatogonial Development and Spermiation after Testosterone-Induced Gonadotropin Suppression in Adult Monkeys (Macaca fascicularis)

O’Donnell¹

2001

Journal of Clinical Endocrinology & Metabolism

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Human male hormonal contraceptive regimens do not consistently induce azoospermia, and the basis of this variable response is unclear. This study used nine adult macaque monkeys (Macaca fascicularis) given testosterone (T) implants for 20 weeks to study changes in germ cell populations in relation to sperm output. Germ cell numbers were determined using the optical disector stereological method. Four animals achieved consistent azoospermia (azoo group), whereas five animals did not (nonazoo group). T-induced gonadotropin suppression in all animals decreased A pale (Ap) spermatogonia to 45% of baseline within 2 weeks, leading to decreased B spermatogonia (32-38%) and later germ cells (20 -30%) after 14 and 20 weeks. Though the reduction in later germ cell types could be primarily attributed to the loss of spermatogonia, the data suggested that some cells were lost during the spermatocyte and spermatid phase of development. B spermatogonial number was more markedly suppressed in azoospermic animals, compared with the nonazoo group, as was the conversion ratio between Ap and B spermatogonia. Abnormal retention of elongated spermatids (failed spermiation) was also prominent in some animals after long-term T administration. We conclude that: 1) the variable suppression of sperm output is attributed to the degree of inhibition of germ cell development from type B spermatogonia onwards, and this is related to the degree of FSH suppression; and 2) inhibition of Ap and B spermatogonial development and of spermiation are the major defects caused by long-term T administration to monkeys. T HE ADMINISTRATION OF exogenous testosterone (T),either alone or in combination with a progestin, reduces the secretion of the pituitary gonadotropins, LH and FSH, and thereby sperm production, and is a promising approach to male contraception (1). A feature of many such contraceptive formulations is the variable induction of azoospermia, ranging from 70 -95%, depending on the regimen and ethnic group under study (1-4). Though sperm counts of less than 3 million per mL may provide adequate contraception (4), there is a general consensus that the reliable induction of azoospermia is important to ensure contraceptive efficacy and the widespread acceptance of male hormonal contraception. An understanding of the biological basis for the variable response is essential to this goal.Although many studies have investigated the effects of hormone suppression on spermatogenesis in the rat (5-7), fewer studies have investigated the effects of FSH and LH/ testicular T suppression on germ cell development in monkeys and man. In monkeys rendered gonadotropin-deficient by hypophysectomy or GnRH antagonist treatment, spermatogonia are the most sensitive germ cell type (8 -11); however, which spermatogonial subtypes are regulated by hormones is controversial (9,(11)(12)(13)(14). A recent study in men receiving weekly injections of T enanthate suggested that the inhibition of spermatogonial development was also the primary lesion in response to go...

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“…It has been known for many years that the testis, especially its rapidly dividing germ cells, is highly sensitive to these treatments. Low doses of cytotoxic drugs or irradiation deplete the differentiating spermatogonia, while less sensitive spermatogonial stem cells survive, and spermatocytes and spermatids continue their maturation to sperm (28). In sexually mature men, testicular involution is a slow process lasting several weeks until temporary or permanent azoospermia is attained.…”

Section: Differences In Germline Stem Cell Biology In Females and Malmentioning

confidence: 99%

Clinical Potential and Putative Risks of Fertility Preservation in Children Utilizing Gonadal Tissue or Germline Stem Cells

et al. 2006

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Depletion of the Spermatogonia from the Seminiferous Epithelium of the Rhesus Monkey after X Irradiation

Cited by 109 publications

References 18 publications

Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia

Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia

Impairment of Spermatogonial Development and Spermiation after Testosterone-Induced Gonadotropin Suppression in Adult Monkeys (Macaca fascicularis)

Clinical Potential and Putative Risks of Fertility Preservation in Children Utilizing Gonadal Tissue or Germline Stem Cells

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