Nuclear Factor-κB Activation in Human Testicular Apoptosis

Pentikäinen, Virve; Suomalainen, Laura; Erkkilä, Krista; Martelin, Eeva; Parvinen, Martti; Pentikäinen, Markku O.; Dunkel, Leo

doi:10.1016/s0002-9440(10)64364-7

Cited by 78 publications

(70 citation statements)

References 70 publications

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“…Therefore, it is likely that a similar mechanism of oestrogen negative feedback occurs in the hypothalamic-pituitary axis in tammar. tESR1 and tESR2 were also found in germ cells at all stages of development, which is consistent with a role in oestrogen-mediated germ cell maintenance and anti-apoptotic ESR1 receptor-mediated cell survival (Couse & Korach 1999, Pentikainen et al 2000. The expression of tESR1 and tESR2 in spermatozoa is similar to that in humans (Durke et al 1998, Aquila et al 2004 in whom oestrogen stimulates sperm motility (Lubahn et al 1993, Korach 1994, Hess et al 1997) and lactate production via ESR1 (O'Donnell et al 2001).…”

Section: Ers In the Developing And Adult Testissupporting

confidence: 68%

Ontogeny of the oestrogen receptors ESR1 and ESR2 during gonadal development in the tammar wallaby, Macropus eugenii

Calatayud¹,

Pask²,

Shaw³

et al. 2010

Reproduction

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Oestrogen has wide ranging effects in development mediated mainly via the two oestrogen receptors, a (ESR1, also known as ERa) and b (ESR2, also known as ERb). Oestrogen is the key factor that directs the indifferent gonad to become an ovary in many non-mammalian vertebrates. Oestrogen is not required for early ovarian differentiation in mammals but can disrupt normal testicular development in eutherians. Surprisingly, exogenous oestrogen can cause sex reversal of an XY gonad in two marsupials, the North American opossum and the tammar wallaby. To understand the mechanism by which oestrogen induces sex reversal, we characterised the genes for ESR1 and ESR2 and examined their expression during gonadal differentiation in the tammar wallaby, Macropus eugenii. Both receptors were expressed in the somatic cells and germ cells of the indifferent gonad in both XX and XY foetuses throughout all stages of development, and persisted in these cells into adulthood. ERs were also present in many other tissues including kidney, pituitary and mammary gland. ER mRNA was not significantly altered by exogenous oestrogen in cultured XY gonads but the receptors translocated to the nucleus in its presence. These findings confirm that there is conserved expression of the ERs in the indifferent gonad despite the lack of available ligand during early gonadal development. The receptors can respond to exogenous estrogen at this early stage and are capable of transducing signals in the early mammalian gonad. However, the selective forces that maintained conserved ER expression in this tissue remain unknown.

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Section: Ers In the Developing And Adult Testissupporting

confidence: 68%

Ontogeny of the oestrogen receptors ESR1 and ESR2 during gonadal development in the tammar wallaby, Macropus eugenii

Calatayud¹,

Pask²,

Shaw³

et al. 2010

Reproduction

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“…The miR-181b inhibits importin-α3 expression, which is an important molecule involved in the NF-kB signaling pathway [50]. NF-kB is a stress responsive transcription factor which actively regulates apoptosis, inflammation [37] and antioxidant enzymes genes [25]. Therefore, downregulation of miR-181b might exert its effect via up-regulation of NF-kB pathway.…”

Section: Discussionmentioning

confidence: 99%

TBHP-induced oxidative stress alters microRNAs expression in mouse testis

Fatemi

Sanati

Shamsara

et al. 2014

J Assist Reprod Genet

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Purpose Reactive oxygen species (ROS) and oxidative stress is one of the main reasons of male infertility. MicroRNAs (miRNAs) regulate multiple intracellular processes. Alterations in miRNAs expression may occur in different conditions and diseases. In this study, the effect of oxidative stress induced by tertiary-butyl hydroperoxide (TBHP) on the expression of candidate miRNAs in mouse testis was investigated.Methods After determining median lethal dose (LD 50 ), TBHP was intraperitoneally (ip) injected at the dilution of 1:10 LD 50 into the adult male mice for 2weeks, and then testis tissues were removed in order to assay the ROS level. Total RNA was extracted and the expression of five miRNAs was quantified by reverse transcription-real time polymerase chain reaction (RT-qPCR).Results The flow cytometry analysis showed a significant increase in ROS level in testis. The expression of three out of five selected miRNAs, including miR-34a, miR-181b and miR-122a, showed some degrees of changes following exposure to oxidative stress. These miRNAs are involved in antioxidant responses, inflammation pathway and spermatogenesis arrest. Conclusions In conclusion, TBHP alters the miRNA expression profile of testis which might play a potential role in oxidative and antioxidative responses and spermatogenesis.

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“…Up to 75% of germ cells undergo death by apoptosis in testis during the pubertal maturation process (Giampietri et al 2005). On the other hand, androgens are known to inhibit apoptosis of male germ cells (Erkkila et al 1997, Pentikainen et al 2000 and testosterone withdrawal stimulates their apoptosis (Nandi et al 1999, Tesarik et al 2002. Germ cell apoptosis induced by androgen deprivation seems to be associated with caspases activation (Vera et al 2006, Johnson et al 2008.…”

Section: Discussionmentioning

confidence: 99%

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

Laurentino

Correia

Cavaco³

et al. 2011

Reproduction

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Regucalcin (RGN) is a calcium (Ca 2C )-binding protein which regulates intracellular Ca 2C homeostasis by modulating the activity of enzymes regulating Ca 2C concentration and enhancing Ca 2C -pumping activity. Several studies have described the pivotal role of proper Ca 2C homeostasis regulation to spermatogenesis and male fertility. Recently, RGN was identified as a sex steroid-regulated gene in prostate and breast; however, a possible role of RGN in spermatogenesis has not been examined. In this study, the expression and localization of RGN in rat and human testis, and other rat reproductive tissues was analyzed. Moreover, we studied whether RGN protein was present in seminiferous tubule fluid (STF). Finally, we examined the effect of 5a-dihydrotestosterone (DHT) on the expression of Rgn mRNA in rat seminiferous tubules (SeT) cultured ex vivo. The results presented in this study show that RGN is expressed in Leydig and Sertoli cells, as well as in all types of germ cells of both rat and human testis. RGN is also expressed in rat prostate, epididymis, and seminal vesicles. Moreover, RGN protein is present in rat STF. The results also demonstrate that Rgn expression is age dependent in rat testis, and is upregulated by the non-aromatizable androgen DHT in rat SeT cultured ex vivo. Taken together, these findings indicate that Rgn is a novel androgen-target gene in rat testis and that it may have a role in male reproductive function, particularly in the control of spermatogenesis.

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Nuclear Factor-κB Activation in Human Testicular Apoptosis

Cited by 78 publications

References 70 publications

Ontogeny of the oestrogen receptors ESR1 and ESR2 during gonadal development in the tammar wallaby, Macropus eugenii

Ontogeny of the oestrogen receptors ESR1 and ESR2 during gonadal development in the tammar wallaby, Macropus eugenii

TBHP-induced oxidative stress alters microRNAs expression in mouse testis

Regucalcin is broadly expressed in male reproductive tissues and is a new androgen-target gene in mammalian testis

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