Browsing by Author "Silva, Ana Manuela dos Santos"
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- Regucalcin as one of the guardians of the male reproductive functionPublication . Silva, Ana Manuela dos Santos; Baptista, Cláudio Jorge Maia; Correia, Sara Carina de LimaMale reproductive function is highly sensitive to extrinsic testicular damage or intrinsic modifications, which consequently affects spermatogenesis leading to declined sperm quality and compromised fertility. These reproductive modifications can represent a collateral effect, for example from an oncological therapy, or a natural consequence of living, such as ageing. Currently, due to early diagnostic and high survival rate, young cancer patients are living longer. Nevertheless, approaches to successfully restrain the undesirable secondary effects of oncological therapies are still missing. Furthermore, until recently, the decline in male reproductive function with the advance of age was frequently neglected. Lately, given the trend of modern society to delay the conception of a biological child, the decrease in sperm quality in older subjects has been drawing attention from the scientific community. Indeed, these problems are emerging topics on male fertility. Oxidative stress (OS) is known to be for itself associated with male infertility cases. Also, OS is implicated in radiotherapy and ageing. In this doctoral thesis, we aimed to disclose the potential of regucalcin (RGN) protein to counteract the damaging effects of testicular radiotherapy as well as to attenuate the ageing-associated changes in male reproductive tract. In recent years, RGN protein has been showing to be an important player in spermatogenesis and male fertility, managing the suppression of pro-oxidant and chemical apoptotic stimulus in seminiferous tubules. RGN is a protein widely expressed in testicular cells, and its biological function seems to be vast. Moreover, RGN is also known as Senescence Marker Protein-30 (SMP-30) as a result of its decreased expression with ageing. Recently, high levels of RGN prevented ageing-associated changes in the prostate. Using an in vivo approach, we studied the role of RGN by comparing transgenic rats overexpressing RGN (Tg-RGN) with their wild-type (Wt) counterparts. Ten weeks after rats were subjected to radiotherapy, we verified that RGN was able to mitigate radiation-induced testicular damage because Tg-RGN animals presented less affected sperm parameters as well as lower rate of testicular apoptosis in comparison with Wt rats. Moreover, Tg-RGN animals also presented unaffected sperm parameters in spite of the ageing concomitantly with lower OS levels. Interestingly, we detected an enhanced expression of RGN in irradiated testis as well as in senescent sperm both in Wt and Tg-RGN rats, reinforcing the involvement of RGN in response to stimuli or modifications that can negatively impact male reproduction. Overall, our results are strong evidence about the beneficial role of RGN as a guardian of male reproductive function, suggesting that RGN protein has great potential to be included in strategies to improve, protect, and/or recover male fertility in men undergoing oncological treatment or with advanced age who still intend to have biological descent.
- The protective effect of regucalcin against radiation-induced testicular damagePublication . Silva, Ana Manuela dos Santos; Batista, Cláudio Jorge Maia; Socorro, Sílvia Cristina da Cruz MarquesTesticular cancer is the most common malignancy among young men, and radiation therapy is a generally used as treatment. However, the exposure to radiation has several adverse effects on male fertility. Considering the high survival rates and the age of incidence of this malignancy, it is mandatory to identify effective strategies protecting against radiation-induced testicular damage. Regucalcin (RGN) is a calcium (Ca2+)-binding protein that is broadly expressed in the male reproductive tract. Several studies have demonstrated RGN ability suppressing cell death in different cell types. Previously, our research group showed that RGN overexpression had beneficial effects on spermatogenesis by suppressing chemical-induced apoptosis. Moreover, RGN is upregulated in radioresistant cell lines, suggesting that it also can protect from radiation damage. The present work aimed to evaluate whether RGN may play a role in spermatogenesis recovery after radiation treatment. For this purpose, transgenic rats overexpressing RGN (Tg-RGN) and their wild-type (Wt) counterparts were exposed to X-rays. At ten weeks of recovery after irradiation, the testicular status and the epididymal sperm parameters were evaluated. The expression of RGN and several cell cycle and apoptosis regulators was also evaluated. In addition, the enzymatic activity of caspase-3 was measured. Upon radiation treatment and ten weeks of recovery, both the testicular status and sperm parameters seem to have been less affected by X-rays in Tg-RGN. We also found a diminished expression of p53 and p21, which may indicate the reinitiating of spermatogenesis. Moreover, the reduced activity of caspase-3 detected in Tg-RGN is in accordance with low levels of caspase-8 and increased Bcl-2/Bax ratio, suggesting that these animals are more resistant to testicular apoptosis in response to radiation. RGN expression was significantly enhanced in Wt rats after irradiation, supporting its involvement in the anti-apoptotic response. Altogether, the present findings point out a protective role for RGN overexpression against radiation-induced testicular damage.