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- Effects of the endocrine disruptor vinclozolin in male reproduction: a systematic review and meta-analysisPublication . Feijó, Mariana; Martins, Roberta VL; Socorro, Sílvia; Pereira, L.; Correia, SaraEndocrine-disrupting chemicals have become an issue of scientific and public discussion. Vinclozolin (VNZ) is a fungicide that competitively antagonizes the binding of natural androgens to their receptor, disturbing the function of tissues that are sensitive to these hormones, as is the case of the male reproductive organs. A systematic review with meta-analyses of rodent studies was conducted to answer the following question: Does exposure to VNZ affect sperm parameters and testicular/epididymal weight? The methodology was prespecified according to the Cochrane Handbook for Systematic Reviews and PRISMA recommendations. Sixteen articles met the inclusion criteria, comprising a total of 1189 animals. The risk of publication bias was assessed using the Trim and Fill adjustment, funnel plot, and Egger regression test. Heterogeneity and inconsistency across the findings were tested using the Q-statistic and I2 of Higgins, respectively. Sensitivitywas also analyzed. Statistical analysiswas performed on Comprehensive Meta-Analysis software (Version 2.0), using random models and weighted mean differences along with a 95% confidence interval. Sperm motility, counts, daily sperm production (evidence of publication bias), and epididymis weight were decreased in VNZ-treated animals. Exposure length and dose, as well as the time point of exposure, influenced the obtained results. Despite the moderate/high heterogeneity observed, the sensitivity analysis overall demonstrated the robustness of the findings. The quality scores of the included studies were superior to 4 in a total of 9, then classified as good. The obtained data corroborate the capability of VNZ exposure to disrupt spermatogenic output and compromise male fertility.
- Effect of tert-butyl hydroperoxide in testicular metabolismPublication . Martins, Roberta Vanessa Lopes; Correia, Sara Carina de Lima; Socorro, Sílvia Cristina da Cruz MarquesSpermatogenesis is the complex biological process that transforms spermatogonial stem cells into spermatozoa, and, thus, is the basis of male fertility. It takes place in the seminiferous tubules (SeT) and is highly dependent on the metabolic cooperation established between the somatic Sertoli cells (SCs) and germ cells. SCs are known as the metabolic stores supplying germ cells with adequate amounts of energy substrates. Despite consuming several subtracts, including amino acids like glutamine, SCs prioritize the metabolization of glucose with the production of lactate, the preferred substrate of germ cells. It is widely known that oxidative stress (OS) adversely affects spermatogenesis, disrupting the development of germ cells, and interfering with sperm function, as well as disturbing cell metabolism. Tert-Butyl hydroperoxide (TBHP) is a well-known OS inducer in the testis. Also, TBHP metabolic action have been suggested. It was identified as a regulator of the pentose phosphate pathway. However, the impact of TBHP in testicular metabolism remains unknown. Regucalcin (RGN) is a calcium (Ca2+) -binding protein that has been associated with the control of cell proliferation, apoptosis, OS and metabolism. Recently, our research group have demonstrated that RGN overexpression modulates glucose and glutamine handling by SCs by regulating the expression of several transporters and enzymes involved in glycolysis and glutaminolysis. Furthermore, the protective role of RGN for the germ cell population upon exposure to damaging factors has been suggested. So, is tis liable to hypothesize that RGN may have a similar behavior against TBHP actions disrupting testicular metabolism. In the present dissertation, the impact of TBHP on testicular glucose and glutamine metabolism and the influence of RGN in attenuating its effects were evaluated. Isolated SeT from adult wild-type (Wt) and transgenic rats overexpressing regucalcin (Tg-RGN) were maintained in culture for 24 hours in the presence or absence of TBHP (250 µM). After that, the expression and activity of several regulators of glycolytic metabolism and glutaminolysis were analysed. The results obtained showed an increase in the intracellular content of glucose and lactate in the SeT of both Wt and Tg-RGN animals treated with TBHP. The altered glycolytic profile in response to TBHP was underpinned by the altered expression of glucose transporters in both Wt and Tg-RGN, and increased lactate dehydrogenase activity in the Tg-RGN rats. Moreover, TBHP altered alanine transferase expression and glutaminolysis though the effects differed between Wt and Tg-RGN animals. In turn, RGN overexpression suppressed the glycolytic metabolism in SeT, regardless of TBHP treatment. The present study is the first evidence that TBHP is a potent testicular metabolic disruptor. Furthermore, RGN action was identified as a possible protective mechanism against the damaging effects of TBHP. These findings also emphasize the role of RGN as a metabolic regulator in spermatogenesis, which could have importance in the context of male (in)fertility. Finally, the outcomes achieved herein support further research work to deep clarify the relationship between OS, metabolic alterations and the RGN actions in the SeT.