Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF−/− mice

Elkis, Yoav; Bel, Shai; Lerer-Goldstein, Tali; Nyska, Abraham; Creasy, Dianne M.; Shpungin, Sally; Nir, Uri

doi:10.1016/j.mce.2012.09.003

Cited by 14 publications

(13 citation statements)

References 42 publications

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“…Moreover, there are a variety of factors that have been demonstrated to cause spermatogenetic arrest, including genetic mutation, environmental factors and hormone deficiency (11,12). Testis weight is also an important indicator of overall testicular health, reflecting changes in germ cell loss (13). In the present study, in which the mice were reared in the same environment and conditions, histological examination showed that spermatogenesis was arrested at the spermatocyte stage.…”

Section: Discussionmentioning

confidence: 99%

Pathological changes of testicular tissue in normal adult mice: A retrospective analysis

Xie

Zhu

2014

Experimental and Therapeutic Medicine

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Mouse testicular experimental models are widely used in the study of andrology, reproductive toxicology and pharmacology. Under physiological conditions, a normal adult mouse is usually considered to have normal testes. However, whether normal adult mouse testes exhibit pathological changes has not been evaluated. The objective of this study was to investigate the pathological changes of testicular tissues in normal adult mice. A retrospective analysis of 720 adult male Kunming mice, used in previous studies as controls, was performed. Bilateral testicular tissues were stained with hematoxylin and eosin for pathological examinations. Among the 720 mice, nine had abnormal testes, an incidence of 1.3%. The nine mice with abnormal testes included two with microrchidia (22.2%) while the others had a normal testicular size. The observed pathological changes associated with microrchidia were seminiferous epithelial vacuolation, spermatogenesis arrest at the spermatocyte stage and the absence of sperm in all tubules. In other abnormal testes, pathological alterations included seminiferous epithelial vacuolation, severe hypospermatogenesis and symplasts composed of collapsed spermatids in tubules. The results demonstrate that normal adult male mice exhibit testicular pathological changes. Therefore, the possibility of abnormal testes in normal adult mice must be considered when using mice to establish a testicular experimental model.

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Section: Discussionmentioning

confidence: 99%

Pathological changes of testicular tissue in normal adult mice: A retrospective analysis

Xie

Zhu

2014

Experimental and Therapeutic Medicine

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“…These multi-step processes are tightly controlled and are governed by both extrinsic hormonal signals and intricate intrinsic regulatory cascades. The complexity of the system makes it susceptible to various defects that can jeopardize male fertility [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…The protein is required for both acrosome formation and for efficient removal of the cytoplasm from elongated spermatids [ 3 ]. TMF is also required for maintaining normal levels of testosterone, which in males, is produced mainly in the endoplasmic reticulum (ER) and mitochondria of Leydig cells [ 4 ]. It should be noted that the Golgi apparatus also plays a poorly understood role in the testosterone production and secretion from these cells [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…TMF is also required for maintaining normal levels of testosterone, which in males, is produced mainly in the endoplasmic reticulum (ER) and mitochondria of Leydig cells [ 4 ]. It should be noted that the Golgi apparatus also plays a poorly understood role in the testosterone production and secretion from these cells [ 4 ]. These roles of TMF are manifested during the spermiogenic process, and, while acrosome formation is linked to the Golgi-related function of TMF inside spermatogenic cells, the effect on testosterone secretion may be attributed to its presence in other cells in the male reproductive system, such as Leydig cells [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…It should be noted that the Golgi apparatus also plays a poorly understood role in the testosterone production and secretion from these cells [ 4 ]. These roles of TMF are manifested during the spermiogenic process, and, while acrosome formation is linked to the Golgi-related function of TMF inside spermatogenic cells, the effect on testosterone secretion may be attributed to its presence in other cells in the male reproductive system, such as Leydig cells [ 4 ]. Since unlike most other traits [ 25 , 26 ], TMF -/- spermatids lack any targeting of pro-acrosomal vesicles to the spermatid nuclear envelope, we studied the role of TMF in controlling the functional contribution of the Golgi to the guided generation and trafficking of pro-acrosomal vesicles and acrosome formation.…”

Section: Introductionmentioning

confidence: 99%

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TMF/ARA160 Governs the Dynamic Spatial Orientation of the Golgi Apparatus during Sperm Development

et al. 2015

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TMF/ARA160 is known to be a TATA element Modulatory Factor (TMF). It was initially identified as a DNA-binding factor and a coactivator of the Androgen receptor. It was also characterized as a Golgi-associated protein, which is essential for acrosome formation during functional sperm development. However, the molecular roles of TMF in this intricate process have not been revealed. Here, we show that during spermiogenesis, TMF undergoes a dynamic change of localization throughout the Golgi apparatus. Specifically, TMF translocates from the cis-Golgi to the trans-Golgi network and to the emerging vesicles surface, as the round spermatids develop. Notably, lack of TMF led to an abnormal spatial orientation of the Golgi and to the deviation of the trans-Golgi surface away from the nucleus of the developing round spermatids. Concomitantly, pro-acrosomal vesicles derived from the TMF-/- Golgi lacked targeting properties and did not tether to the spermatid nuclear membrane thereby failing to form the acrosome anchoring scaffold, the acroplaxome, around the cell-nucleus. Absence of TMF also perturbed the positioning of microtubules, which normally lie in proximity to the Golgi and are important for maintaining Golgi spatial orientation and dynamics and for chromatoid body formation, which is impaired in TMF-/- spermatids. In-silico evaluation combined with molecular and electron microscopic analyses revealed the presence of a microtubule interacting domain (MIT) in TMF, and confirmed the association of TMF with microtubules in spermatogenic cells. Furthermore, the MIT domain in TMF, along with microtubules integrity, are required for stable association of TMF with the Golgi apparatus. Collectively, we show here for the first time that a Golgi and microtubules associated protein is crucial for maintaining proper Golgi orientation during a cell developmental process.

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Testosterone promotes GPX5 expression of goat epididymal epithelial cells cultured in vitro

ZhaoJin

Fan

Song

et al. 2019

In Vitro Cell.Dev.Biol.-Animal

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Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF−/− mice

Cited by 14 publications

References 42 publications

Pathological changes of testicular tissue in normal adult mice: A retrospective analysis

Pathological changes of testicular tissue in normal adult mice: A retrospective analysis

TMF/ARA160 Governs the Dynamic Spatial Orientation of the Golgi Apparatus during Sperm Development

Testosterone promotes GPX5 expression of goat epididymal epithelial cells cultured in vitro

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