Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment

Guo, Jingjing; Zhou, Hongyu; Su, Zhijian; Chen, Bingbing; Wang, Guimin; Wang, Claire Q F; Xu, Yunfei; Ge, Ren‐Shan

doi:10.1530/rep-12-0465

Cited by 94 publications

(116 citation statements)

References 27 publications

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“…The pubertal development of Leydig cells can also be mimicked by the regeneration of Leydig cells after a single intraperitoneal injection of 75 mg/kg ethane dimethane sulfonate (EDS) to the rat. On day 7 after EDS treatment, adult Leydig cells were completely eliminated 10 . On days 21, 35, and 56 after EDS treatment, Leydig cell regeneration progressed through progenitor, immature, and adult stages, as visualized by the staining of 3β-HSD1 (Leydig cell lineage biomarker) and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1, the immature and adult Leydig cell biomarker) 10 .…”

Section: Introductionmentioning

confidence: 99%

A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis

Guo

Wang

et al. 2017

Sci Rep

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Cadmium is an endocrine disruptor, impairing male reproduction. The objective of this study is to investigate whether cadmium affects rat Leydig cell regeneration and to dissect the underlying mechanism. Adult male Sprague-Dawley rats received a single intraperitoneal injection (i.p.) of 0, 0.5 or 1.0 mg/kg of cadmium chloride, followed by ethane dimethane sulfonate (EDS) treatment to eliminate adult Leydig cells 20 days later. Compared to control (0 dose), cadmium treatment reduced serum testosterone levels by days 21, 35, and 56 after EDS treatment. Serum luteinizing hormone (LH) levels were also affected by day 56, the only time point examined. There were fewer regenerated Leydig cells in the cadmium-treated testis on days 35 and 56 after EDS treatment. Further studies demonstrated that the mRNA or protein levels of Leydig (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, and Hsd11b1), non-Leydig (Fshr and Dhh), and gonadotroph (Lhb) cells were also significantly lower in cadmium-treated animals. Since LH and desert hedgehog (DHH) are critical factors for Leydig cell differentiation, our result demonstrated that the lower doses of cadmium exposure, even briefly, may permanently damage Leydig cell regeneration.

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Section: Introductionmentioning

confidence: 99%

A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis

Guo

Wang

et al. 2017

Sci Rep

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“…Because testosterone is the major androgen produced by adult rat Leydig cells and DIOL is the major androgen produced by immature Leydig cells [10,27], serum testosterone and DIOL concentrations were measured with a tritium-based radioimmunoassay, as described [28]. Inter-assay and intra-assay variations of the testosterone and DIOL were between 7% and 8%.…”

Section: Methodsmentioning

confidence: 99%

“…This pattern of development recapitulates the process of Leydig cell development in the growing rat. For example, MSC-derived progenitor Leydig cells gradually differentiate into immature Leydig cells from days 21 to 28 and, then, into mature adult Leydig cells on day 56 day post-EDS treatment [8,10]. In the middle of the regeneration, 5α-androstane-3α,17β-diol (DIOL) is the primary androgen, which is produced by immature Leydig cells, due to the high expression of 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase [8,10].…”

Section: Introductionmentioning

confidence: 99%

“…For example, MSC-derived progenitor Leydig cells gradually differentiate into immature Leydig cells from days 21 to 28 and, then, into mature adult Leydig cells on day 56 day post-EDS treatment [8,10]. In the middle of the regeneration, 5α-androstane-3α,17β-diol (DIOL) is the primary androgen, which is produced by immature Leydig cells, due to the high expression of 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase [8,10]. It was observed that the E2 effects on rat Leydig cell regeneration depends on the time of exposure to this agent [7].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

Chen

Jiang

et al. 2014

IJMS

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The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

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“…This is important because it shows that Leydig cell stem cells persist in the adult testis and that the potential exists to regenerate Leydig cells in situations such as ageing where Leydig number and/or activity is reduced (Chen et al ., 1996). In addition, Leydig cell re‐generation after EDS appears to closely resemble normal development of the adult Leydig cell population thereby providing a model system for study of this process (Teerds & Rijntjes, 2007; Guo et al ., 2013). The advantages of this model over normal development are that the interstitium is clear of Leydig cells and so there can be no confusion between developing and mature Leydig cells, other developmental events in the testis are not occurring simultaneously and hormone levels can be more easily manipulated in the more mature animals.…”

Section: Leydig Cellsmentioning

confidence: 99%

Cell‐specific ablation in the testis: what have we learned?

2015

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SummaryTesticular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.

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Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment

Cited by 94 publications

References 27 publications

A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis

A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis

Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

Cell‐specific ablation in the testis: what have we learned?

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