Copper Nanoparticles Show Obvious in vitro and in vivo Reproductive Toxicity via ERK Mediated Signaling Pathway in Female Mice.

Copper nanoparticles (Cu-NPs) and other inorganic nanomaterials have caused increasing concern owing to be widely used. Early studies have reported that they can result in injuries to the kidney, liver and spleen of mice; cause embryonic damage; and inhibit the reproductive capacity of red worms. However, few studies have reported the toxicity of Cu-NPs on the reproductive systems of mammals. In the present work, we explored the cytotoxicity of Cu-NPs in human extravillous trophoblast cells and in the reproductive organs of mice. Cu-NPs induced ovarian and placental pathophysiology and dysfunction in mice. These nanoparticles also induced apoptosis and suppressed the proliferation of human extravillous trophoblast cells and caused cell cycle arrest at the G2/M phase in a time-and dose-dependent manner. Cu-NPs can significantly damage the mitochondrial membrane potential (MMP), which suggests that Cu-NPs can activate the mitochondria-mediated apoptosis signaling pathway. We also observed that Cu-NPs significantly inhibit the expression of BRAF, ERK, and MITF expression, all of which are important genes in the ERK signaling pathway. Our research demonstrated that Cu-NPs exert obvious reproductive toxicity in mice by disrupting the balance of sex hormones and exert cytotoxicity on human extravillous trophoblast cells, and ERK signaling and the mitochondrial apoptosis pathway made great contribution to the toxicity of Cu-NPs on female mice.

Testosterone, Estradiol, and Sex Hormone-Binding Globulin in Alzheimer's Disease: A Meta-Analysis.

BACKGROUND: Previous studies suggested that plasma sex hormones may be implicated in the pathogenesis of Alzheimer's disease (AD). However, the relationship between sex hormones and AD remains unclear. OBJECTIVE: To systematically review and quantitatively analyze studies observing plasma total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels among AD patients. METHODS: Medline, EMBASE, the Cochrane Library, and PsycINFO were searched for studies published prior to March 28(th), 2014. Published studies that reported plasma levels of TT, E2, and SHBG in AD and matched controls were included in the present meta-analysis. RESULTS: Meta-analysis was performed using the random effects model, expressing continuous outcomes as the mean difference (MD) between AD and control populations. The 95% confidence intervals (CI) were also calculated. No differences were found in plasma levels of TT and E2 between AD and matched controls (TT MD -0.17 nmol/l, 95% CI -0.54, 0.20; E2 MD -1.16 pmol/l, 95% CI -9.85, 6.83). Plasma levels of SHBG were significantly increased in AD patients compared to healthy controls (SHBG MD 12.94 nmol/l, 95% CI 2.68, 23.20). CONCLUSION: Patients with AD had higher plasma levels of SHBG. The up-regulated levels of plasma SHBG show preliminary supportive evidence that SHBG and the bioavailability of functional sex hormones in plasma may be linked to the pathogenesis of AD.

Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats.

OBJECTIVE: The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1-Bcl-2 interaction, were investigated. METHODS: Male Sprague-Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson's trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum. RESULTS: Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-ß1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration. CONCLUSIONS: Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1-Bcl-2 interaction.