Immunophilin FK506-binding protein 52 (FKBP52) is a cochaperone that binds to the progesterone receptor (PR) to optimize progesterone (P 4 )-PR signaling. We recently showed that Fkbp52-deficient (Fkbp52 −/− ) mice have reduced uterine PR responsiveness and implantation failure which is rescued by excess P 4 supplementation in a genetic background-dependent manner. This finding led us to hypothesize that FKBP52 has functions in addition to optimizing PR activity. Using proteomics analysis, we found that uterine levels of peroxiredoxin-6 (PRDX6), a unique antioxidant, are significantly lower in Fkbp52 −/− mice than in WT and PR-null (Pgr −/− ) mice. We also found that Fkbp52 −/− mice with reduced uterine PRDX6 levels are susceptible to paraquat-induced oxidative stress (OS), leading to implantation failure even with P 4 supplementation. The same dose of paraquat did not interfere with implantation in WT mice. Moreover, treatment with antioxidants α-tocopherol and N-acetylcysteine (NAC) attenuated paraquat-induced implantation failure in P 4 -treated Fkbp52 −/− mice. Functional analyses using mouse embryonic fibroblasts show that Fkbp52 deficiency associated with reduced PRDX6 levels promotes H 2 O 2 -induced cell death, which is reversed by the addition of NAC or by forced expression of PRDX6, suggesting that Fkbp52 deficiency diminishes the threshold against OS by reducing PRDX6 levels. These findings provide evidence that heightened uterine OS in Fkbp52 −/− females with reduced PRDX6 levels induces implantation failure even in the presence of excess P 4 . This study shows that FKBP52-PRDX6 signaling protects pregnancy from overt OS.embryo implantation | mouse | uterus

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In this study, the effect of testosterone on gastrocnemius muscle fibres in growing and adult rats (male and female) was examined using histochemical, morphometric and ultrastructural techniques. After physiological saline (PS), olive oil (OvO) or olive oil + testosterone (OvOT) injections on 72 rats (growing and mature, 36 male and 36 female), the sample tissues of fibre types of the gastrocnemius muscle taken were examined by histochemical [alkaline adenosine triphosphatase (alk-ATPase), acid ATPase (ac-ATPase)], morphometric and ultrastructural techniques. In PS-injected control groups, the gastrocnemius muscle of both sexes contained all the fibre types studied [slow-oxidative muscle fibres (type I), fast-oxidative glycolytic muscle fibres (type IIA) and fast-glycolytic muscle fibres (type IIB)]. The type I fibres had the smallest diameter, type IIA had a medium diameter and type IIB fibres had the largest diameter. In OvO-injected groups, it was observed that the OvO had little effect on the gastrocnemius muscles of either sex, although there was significant enlargement of type IIB fibres. After the injection of OvOT, hypertrophy of muscle fibres was determined by morphometric study. The biggest increase in diameter was on type I fibres. In addition, degenerations on some mitochondria, accumulation of lipid droplets on type I and type II fibres, an increase in glycogen particles, bifurcation of myofibrils, an increase in the number and diameter of units resembling T tubules and an increase in ribosomal content were also observed in the same group by transmission electron microscope. Consequently, it was determined that testosterone can induce protein synthesis in gastrocnemius muscle fibres, and induces changes in shape and size, and also can change the appearance and the number of fibres.

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The purpose of this experiment was to compare the weight, insulinlike growth factor-I (IGF-I) expression, and ultrastructure of the soleus muscle in growing castrated rats treated with testosterone or melatonin. In this study, adult male Wistar albino rats were used. The groups were arranged as sham, castrated, and testosterone-or melatonin-injected groups after castration. The soleus muscle samples were fixed in Bouin's solution for immunohistochemistry, and in 2.5% gluteraldehyde in 0.1 M phosphate buffer (pH 7.4). Whereas castration reduced the soleus weight and fiber diameter, testosterone and melatonin administration increased them. IGF-I immunostaining observed in the satellite cells and periphery of the myofibers was least intense in the castrated group. Strong staining of IGF-I was observed in the testosterone-and melatonin-administered groups. The ultrastructure of the soleus muscle in castrated animals showed the important ultrastructural modifications related to degeneration. In these groups, degenerative mitochondria, glycogen clusters under the sarcolemma, irregular Z lines, and loss of lamina externa were observed. The ultrastructure of myofibrils in the testosterone-and melatonin-injected groups was similar to that in sham groups in view of structure. In conclusion, we suggest that melatonin is as effective as testosterone in the prevention of atrophy induced by castration through the IGF-I axis.

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