Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions

Pinon‐Lataillade, Ghislaine; Mc, Viguier-Martinez; Touzalin, AM; Maas, J.; Jégou, Bernard

doi:10.1051/rnd:19910602

Cited by 26 publications

(21 citation statements)

References 29 publications

(50 reference statements)

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“…Consequently, we suppose that an increase of germ cell death could modify the production of proteins or other factors by Sertoli cells. Indeed, some authors have suggested that a diminution of ABP production by Sertoli cells in c-irradiated rats could have been due to germ cell death caused by radiation (Pinon-Lataillade et al 1991;Guitton et al 2000). Based on these authors' data, we suppose that the transferrin labeling diminution observed in Sertoli cells of etoposide-treated groups occurred due to the loss of germ cells, since etoposide caused an increase of apoptotic germ cell death in rats treated during prepubertal phase, as previously demonstrated by us (Stumpp et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Sertoli cell function in albino rats treated with etoposide during prepubertal phase

Stumpp

Freymüller

Miraglia

2006

Histochem Cell Biol

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Sertoli cell plays a key role in spermatogenesis. Many studies refer that this cell is not harmed by the majority of anticancer treatments known to cause damage to the testis. However, in the previous study we observed that etoposide, an efficient chemotherapeutic drug, provokes an increase in numerical density of the Sertoli cells. This phenomenon suggests that this cell was harmed by etoposide. Thus, we decided to investigate a possible direct action of etoposide on Sertoli cells analyzing the function of this cell and relating it with the integrity and damage of the seminiferous epithelium. Prepubertal albino rats received 5 mg/kg of etoposide for eight consecutive days and were sacrificed in different ages. The control groups received 0.9% saline solution. The testes were fixed in Bouin's liquid for transferrin immunolabeling and testicular labeled tissue volume density measurement. Except for the younger rats, all the etoposide-treated rats showed diminution of transferrin immunolabeling in the seminiferous epithelium, and consequently, of total labeled testicular tissue volume density. We concluded that the diminution of transferrin labeling in the seminiferous epithelium was not associated with germ cell absence such as commonly reported. The results suggest etoposide impairs Sertoli cell function.

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Section: Discussionmentioning

confidence: 99%

Sertoli cell function in albino rats treated with etoposide during prepubertal phase

Stumpp

Freymüller

Miraglia

2006

Histochem Cell Biol

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“…In Wistar [22] or Sprague-Dawley rats [29] there was a 50-70% increase in serum FSH following 5 Gy to 20 Gy irradiation of testes; serum LH was increased 1.4-to 4-fold. In these studies, no recovery of spermatogenesis was seen after 5-20 Gy.…”

Section: Serum Hormone Levels After Irradiationmentioning

confidence: 92%

Failure of Spermatogenesis to Recover Despite the Presence of A Spermatogonia in the Irradiated LBNF1 Rat1

Kangasniemi

Huhtaniemi

Meistrich

1996

Biology of Reproduction

112

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The dose and time response of LBNF1, rat testis to gamma irradiation was studied with use of single doses from 2.5 Gy to 6.0 Gy. Germ cells were initially depleted as a result of killing the radiosensitive differentiating spermatogonia. Some recovery of spermatogenesis was observed at 4 and 6 wk after irradiation as indicated by the repopulation of tubules with germ cells derived from surviving stem spermatogonia. Although spermatogenesis showed additional recovery and was maintained throughout the 60-wk follow-up period after 2.5 Gy, at doses from 3.5 Gy to 6.0 Gy, repopulation indices declined after 6 wk to less than 2%. The numbers of Sertoli cells per nonrepopulating tubule were constant, independent of radiation dose or time. In addition, the nonrepopulating tubules contained an average of one A spermatogonium per 100 Sertoli cells. The size and shape of these cells corresponded to undifferentiated A spermatogonia in nonirradiated control tests. Despite high labeling (40%) and mitotic (20%) indices, the numbers of A spermatogonia changed very little with time, and no differentiated cells were produced in these tubules. The failure of spermatogenesis to recover was not due to hormone deficiency: serum gonadotropin levels increased after irradiation, and serum testosterone remained at control levels. The irradiated LBNF1 rat model may be useful for studying the regulation of differentiation of A spermatogonia.

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“…In contrast to nongenotoxic agents, the only genotoxic agents that have any hormonal or mechanistic data are cadmium (Bomhard et al, 1987;Laskey and Phelps, 1991;Waalkes and Rehm, 1992), dibromochloropropane (DBCP) (Cortes-Gallegos et al, 1980;), and radiation (Lindsay et al, 1969;Pinon-Lataillade et al, 1991). These compounds are discussed below.…”

Section: B Genotoxic Compoundsmentioning

confidence: 99%

“…The incidence of LCTs was 1/45 (2/2%), 6/62 (9.7%), and 40/74 (54%) in the control, 150R, and 500R groups, respectively. The ability of radiation to induce LCTs may be related to increased LH levels (Pinon-Lataillade et al, 1991), possibly secondary to tubule damage. Interestingly, other radiation studies with rats did not demonstrate an association with radiation and LCT formation (Hulse, 1977;Anisimov and Osipova, 1993).…”

Section: Radiationmentioning

confidence: 99%

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

Cook

Klinefelter

Hardisty

et al. 1999

Critical Reviews in Toxicology

175

122

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Leydig cells (LCs) are the cells of the testis that have as their primary function the production of testosterone. LCs are a common target of compounds tested in rodent carcinogenicity bioassays. The number of reviews on Leydig cell tumors (LCTs) has increased in recent years because of its common occurrence in rodent bioassays and the importance in assessing the relevance of this tumor type to humans. To date, there have been no comprehensive reviews to identify all the compounds that have been shown to induce LCTs in rodents or has any review systematically evaluated the epidemiology data to determine whether humans were at increased risk for developing LCTs from exposure to these agents. This review attempts to fill these deficiencies in the literature by comparing the cytology and ontogeny of the LC, as well as the endocrine and paracrine regulation of both normal and tumorigenic LCs. In addition, the pathology of LCTs in rodents and humans is compared, compounds that induce LC hyperplasia or tumors are enumerated, and the human relevance of chemical-induced LCTs is discussed. There are plausible mechanisms for the chemical induction of LCTs, as typified by agonists of estrogen, gonadotropin releasing hormone (GnRH), and dopamine receptors, androgen receptor antagonists, and inhibitors of 5alpha-reductase, testosterone biosynthesis, and aromatase. Most of these ultimately involve elevation in serum luteinizing hormone (LH) and/or LC responsiveness to LH as proximate mediators. It is expected that further work will uncover additional mechanisms by which LCTs may arise, especially the role of growth factors in modulating LC tumorigenesis. Regarding human relevance, the pathways for regulation of the hypothalamo-pituitary-testis (HPT) axis of rats and humans are similar, such that compounds that either decrease testosterone or estradiol levels or their recognition will increase LH levels. Hence, compounds that induce LCTs in rats by disruption of the HPT axis pose a risk to human health, except for possibly two classes of compounds (GnRH and dopamine agonists). Because GnRH and prolactin receptors are either not expressed or are expressed at very low levels in the testes in humans, the induction of LCTs in rats by GnRH and dopamine agonists would appear not to be relevant to humans; however, the potential relevance to humans of the remaining five pathways of LCT induction cannot be ruled out. Therefore, the central issue becomes what is the relative sensitivity between rat and human LCs in their response to increased LH levels; specifically, is the proliferative stimulus initiated by increased levels of LH attenuated, similar, or enhanced in human vs. rat LCs? There are several lines of evidence that suggest that human LCs are quantitatively less sensitive than rats in their proliferative response to LH, and hence in their sensitivity to chemically induced LCTs. This evidence includes the following: (1) the human incidence of LCTs is much lower than in rodents even when corrected for detection bias; (2) several ...

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Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions

Abstract: Summary ― Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of y rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in

Cited by 26 publications

References 29 publications

Sertoli cell function in albino rats treated with etoposide during prepubertal phase

Sertoli cell function in albino rats treated with etoposide during prepubertal phase

Failure of Spermatogenesis to Recover Despite the Presence of A Spermatogonia in the Irradiated LBNF1 Rat1

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

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