Partial wave in human seminiferous tubules appears to be a random occurrence

Johnson, Larry; McKenzie, Kenneth S.; Snell, J.

doi:10.1016/s0040-8166(96)80001-2

Cited by 30 publications

(19 citation statements)

References 20 publications

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“…1) were easily identified in histological sections of seminiferous tubules by their characteristic morphology and location close to the lumen of the tubule (40,41). After LCM, the cells were lysed and diluted to less than one haploid genome equivalent per sample, and the HD TNR tract was amplified by using single-molecule PCR.…”

Section: Resultsmentioning

confidence: 99%

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Huntington disease expansion mutations in humans can occur before meiosis is completed

Yoon

Dubeau

Young

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Single-molecule DNA analysis of testicular germ cells isolated by laser capture microdissection from two Huntington disease patients showed that trinucleotide repeat expansion mutations were present before the end of the first meiotic division, and some mutations were present even before meiosis began. Most of the larger Huntington disease mutations were found in the postmeiotic cell population, suggesting that expansions may continue to occur during meiosis and͞or after meiosis is complete. Defining the germ-line cell compartments where the trinucleotide repeat expansions occur could help to elucidate the underlying mechanisms of instability.A t least 14 diseases result from expansion in the number of trinucleotide repeats (TNR) in or adjacent to a proteincoding gene (1-3). In most cases, the repeat sequence consists of CAG͞CTG triplets. The expanded alleles characteristically undergo further expansion when the disease gene is transmitted from an affected parent to the offspring, resulting in increased disease severity and an earlier age of onset. Based on studies in model systems, a variety of molecular mechanisms have been proposed to explain TNR expansion, including meiotic recombination (4-7), DNA replication slippage (2,(8)(9)(10)(11)(12)(13)(14), and DNA damage repair (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Whether one or all of these processes actually contribute to germ-line expansion mutations in humans is not known, although it is widely accepted that secondary structure formation by TNR tracts is a critical step in the mutation process (reviewed in refs. 2 and 25-28).Defining the germ-line cell compartments where the TNR expansions occur in humans could help reveal the underlying mechanisms. The presence of expansion mutations in spermatogonia would be consistent with a mitotic mutation process mediated by replication slippage or DNA damage repair. Expansions occurring during meiosis might suggest a role for double strand break formation induced by the SPO11 protein (29-31), whereas expansions after meiosis is completed would implicate DNA damage repair.No direct information on the presence or absence of CAG͞ CTG expansion mutations in the various human germ-line cell compartments is available. We investigated the germ line of two men who died from Huntington disease (HD). When men transmit the HD mutation, the relative increase in repeat number among their offspring [or in their sperm (32)] is among the highest observed for CAG͞CTG tract instability (reviewed in ref. 33). We analyzed testicular germ cells isolated by laser capture microdissection (LCM) (34). We showed that TNR expansion mutations are present before the end of the first meiotic division, and are even present before meiosis begins. Because a greater proportion of the larger human mutations were found in the postmeiotic cell population, we propose that some expansions may continue to occur after the beginning of meiosis. In humans, TNR mutations may arise at different stages of germ-line development, possibly as a result of several d...

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Section: Resultsmentioning

confidence: 99%

“…Synchronization of cell division of spermatogonia along the length of seminiferous tubules is limited in humans compared with rodents (40,41). Human premeiotic and meiotic cells are readily identified based on their size, nuclear staining properties, and close proximity to the basement membrane (42).…”

Section: Resultsmentioning

confidence: 99%

Huntington disease expansion mutations in humans can occur before meiosis is completed

Yoon

Dubeau

Young

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Im Un ter schied zu Na gern oder grö ße ren Säu-gern wie Hund, Pferd, Schwein oder Rind fin det man beim Men schen und den großen Men schaf fen auf ge ge be nen Tu bu lusquer schnit ten im mer mehr als ein Sta dium (mul ti-sta ge ar ran ge ment vs. sin glesta ge ar ran ge ment), [10,21] …”

Section: Ki Ne Tik Der Sper Ma To Ge Ne Seunclassified

Spermatogenese

Bergmann

2005

Urologe

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Spermatogenesis takes place within the testicular seminiferous tubules which consist of the peritubular lamina propria and the seminiferous epithelium. The latter is composed of germ cells and somatic Sertoli cells. Sertoli cells trigger germ cell development by mediating follicle-stimulating hormone and androgen hormonal stimuli.Spermatogenesis comprises proliferation of spermatogonia, meiosis of spermatocytes, and differentiation of spermatids into spermatozoa (spermiogenesis). There are six distinct and specific germ cell associations (I-VI). These "stages of spermatogenesis" occur sequentially along the length of a tubule. Different defects in spermatogenesis occur in adjacent seminiferous tubules (mixed atrophy) and are associated with deficits in differentiation of Sertoli cells. Biopsy specimens should be fixed in Bouin's solution. Diagnosis of preinvasive carcinoma in situ is based on the immunohistochemical demonstration of placental-like alkaline phosphatase (PLAP), which is expressed exclusively in carcinoma in situ cells. Histological evaluation should be performed using a score count system, and the use of histological techniques for protein and mRNA expression. Testicular biopsy should only be performed in accordance with strict indication criteria, and histological evaluation should be carried out in specialist centres, i.e. as recommended by the European Academy of Andrology (EAA).

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“…In man the cycle can only be divided into six stages. There is a mixed and apparently random population of cells types and even different stages of the same cell type within the tubules (Johnson et al, 1996). This randomness and asynchrony give an additional value to the mouse as a "model organism"!…”

Section: Mouse Testis Sections and Synchronization Of Meiotic Prophasmentioning

confidence: 99%

The mouse “tool box” for meiotic studies

Ashley

2004

Cytogenet Genome Res

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Besides availability, there are numerous advantages to using mice for meiotic studies: (1) techniques exist for enriching the population of spermatocytes at particular meiotic stages; (2) spermatogenesis in mice is highly synchronized and testis sections afford a highly accurate method of staging meiotic events; (3) knock-out mice provide a rich source of meiotic mutants. Coupled with antibody localization techniques these tools, singularly and in combination, provide multiple means of temporally and physically dissecting meiosis.

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Partial wave in human seminiferous tubules appears to be a random occurrence

Cited by 30 publications

References 20 publications

Huntington disease expansion mutations in humans can occur before meiosis is completed

Huntington disease expansion mutations in humans can occur before meiosis is completed

Spermatogenese

The mouse “tool box” for meiotic studies

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