[Expression of G-protein coupled estrogen receptor in the testis of the male mouse with kidney yin or kidney yang deficiency and its impact on the reproductive function of the mouse].

OBJECTIVE: To investigate the expression of the G-protein coupled estrogen receptor (GPER) in the testis of the male mouse with kidney yin or kidney yang deficiency and its influence on the reproductive function of the mouse. METHODS: We randomized 30 six-week-old male Kunming mice into three groups of equal number: kidney yang deficiency, kidney yin deficiency, and normal control, and established the models of kidney yang deficiency and kidney yin deficiency by peritoneal injection of hydrocortisone at 50 mg/kg for 5 days and 25 mg/kg for 10 days, respectively. We observed the behavioral changes of the mice using the elevated plus-maze, exhaustive swimming and field experiment, examined the semen quality with the automatic sperm quality analyzer, calculated the average number of the offspring, measured the serum testosterone (T) and estradiol (E2) levels and T/E2 ratio by Roche electrochemiluminescence assay, and determined the localization and expression of GPER in the testis by immunohistochemistry and immunofluorescence staining. RESULTS: Compared with the mice with kidney yin deficiency, those with kidney yang deficiency showed remarkably fewer entries into the open arm and central area (P <0.05) and shorter time of exhaustive swimming (P <0.05), but no statistically significant difference in the time spent in the open arm or the central area (P >0.05); the latter group also exhibited significant decreases in the epididymal sperm count (ï¼»7.27 ± 1.30ï¼½ vs ï¼»3.05 ± 1.06ï¼½ ×108/g, P <0.01), sperm motility (ï¼»54.15 ± 13.52ï¼½ vs ï¼»51.57 ± 8.75ï¼½ %, P <0.01) and average number of the offspring (6.46 vs 4.33, P <0.05), a slight increase in the rate of morphologically abnormal sperm (ï¼»13.42 ± 2.32ï¼½ vs ï¼»15.39 ± 2.48ï¼½ %, P >0.05), and markedly reduced serum T (ï¼»24.96 ± 6.18ï¼½ vs ï¼»16.72 ± 5.92ï¼½ ng/dl,P <0.05), E2 (ï¼»19.81 ± 4.01ï¼½ vs ï¼»15.24 ± 1.11ï¼½ pg/ml,P <0.05) and T/E2 ratio (1.41 vs 1.25, P <0.05). The expression of GPER was found in the cytoplasm of the Leydig cells, negative in the nuclei and cell membrane, significantly higher in the kidney yang than in the kidney yin deficiency group (P <0.05). CONCLUSIONS: The numbers of sperm and offspring decreased while the percentage of morphologically abnormal sperm increased in both the kidney yang and kidney yin deficiency mice, even more significantly in the former, which might be associated with the up-regulated expression of GPER in the testis of the mouse with kidney yang deficiency and consequently the reduced serum T level and T/E2 ratio.

Antihypertensive drugs use and the risk of prostate cancer: a meta-analysis of 21 observational studies.

BACKGROUND: Due to the lack of strong evidence to identify the relationship between antihypertensive drugs use and the risk of prostate cancer, it was needed to do a systematic review to go into the subject. METHODS: We systematically searched PubMed, Web of Science and Embase to identify studies published, through May 2015. Two evaluators independently reviewed and selected articles involving the subject. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the studies. All extracted results to evaluate the relationship between antihypertensive drugs usage and prostate cancer risk were pool-analysed using Stata 12.0 software. RESULTS: A total of 12 cohort and 9 case-control studies were ultimately included in our review. Most of the studies were evaluated to be of high quality. There was no significant relationship between angiotensin converting enzyme inhibitors (ACEI) usage and the risk of prostate cancer (RR 1.07, 95% CI 0.96-1.20), according to the total pool-analysed. Use of angiotensin receptor blocker (ARB) was not associated with the risk of prostate cancer (RR 1.09, 95% CI 0.97-1.21), while use of CCB may well increase prostate cancer risk based on the total pool-analysed (RR 1.08, 95% CI 1-1.16). Moreover, subgroup analysis suggested that use of CCB clearly increased prostate cancer risk (RR 1.10, 95% CI 1.04-1.16) in terms of case-control studies. There was also no significant relationship between use of diuretic (RR 1.09, 95% CI 0.95-1.25) or antiadrenergic agents (RR 1.22, 95% CI 0.76-1.96) and prostate cancer risk. CONCLUSIONS: There is no significant relationship between the use of antihypertensive drugs (ACEI, ARB, beta-blockers and diuretics) and prostate cancer risk, but CCB may well increase prostate cancer risk, according to existing observational studies.

Gold nanoparticle-based miR155 antagonist macrophage delivery restores the cardiac function in ovariectomized diabetic mouse model.

Diabetic cardiomyopathy is a common disease in postmenopausal women, in whom the estrogen deficiency aggravates the pathology. In this study, we have found that estrogen deficiency due to ovariectomy aggravates the inflammation in the hearts of diabetic mice, as depicted by excessive proinflammatory type 1 macrophages (M1) over anti-inflammatory type 2 macrophages (M2). Accordingly, an additional increase of reactive oxygen species, cell apoptosis, cardiac hypertrophy, and fibrosis was observed in the hearts of ovariectomized diabetic mice, in comparison with the diabetes-only group. Significantly, miR155, a potent promoter of M1 polarization, was found to be additionally enhanced in the macrophages and hearts by ovariectomy. Tail vein injection of miR155-AuNP, in which thiol-modified antago-miR155 was covalently conjugated with gold nanoparticle (AuNP), preferentially delivered the nucleic acids into the macrophages via phagocytosis. Together with the increased M2 ratio and reduced inflammation, in vivo delivery of antago-miR155 reduced cell apoptosis and restored the cardiac function. The restoration efficacy of miR155-AuNP was much better than general macrophage depletion by clodrosome. In summary, we revealed that M1/M2 imbalance contributes to the aggravated cardiomyopathy in ovariectomized diabetic mice, and therapeutically reducing miR155 in macrophages by AuNP serves as a promising strategy in improving cardiac function.

Diosgenin stimulates rat TM4 cell proliferation through activating plasma membrane translocation and transcriptional activity of estrogen receptors.

Sertoli cells (SCs) function as "nurse cells," which play crucial roles in supporting spermatogenesis through establishing a unique and essential environment in the male reproductive tract. Given the important roles of SCs in male fertility, this study was designed to evaluate the effect of diosgenin, an aglycone of the steroidal saponin, on TM4 cell proliferation and to elucidate the possible mechanisms. We showed that diosgenin increased the proliferation of TM4 cell and primary SCs in a time- and concentration-dependent manner. Diosgenin increased cyclins D1 and E as well as CDK4/6 and CDK2 expression but inhibited P27 expression, with no significant alterations of cyclin B and cdc2 (cell division cycle 2), resulting in cell-cycle G1/S transition. Diosgenin significantly inhibited apoptosis, as reflected by decreased percentage of TUNEL-positive cells; decreased expression of Bax (Bcl-2-associated X protein), AIF (apoptosis-inducing factor), and cleaved caspases 3 and 9; and increased expression of Bcl-2 (B-cell lymphoma 2). Diosgenin induced an immediate and transient plasma membrane translocation of ESR1 and ESR2 from the nucleus, which was inhibited by the antiestrogen ICI 182 780 and PP2, an inhibitor of SRC. Moreover, ICI 182 780 and PP2 significantly inhibited diosgenin-induced cell-cycle transition and inhibition of apoptosis. Activation of extracellular regulated protein kinase (ERK)/Akt signaling was also involved in diosgenin-induced TM4 cell proliferation, which was SRC- and ESR-dependent. Furthermore, diosgenin induced late activation of nuclear ESR transcriptional activity, which in turn directly regulated cell cycle and apoptosis-related factors, such as cyclin D and Bcl-2. Taken together, the results show that diosgenin activated SRC-ESR translocation-ERK/Akt-ESR transcriptional activity, leading to cell-cycle transition and inhibition of apoptosis and thus final cell proliferation. These findings may better our understanding of the pharmacological actions of diosgenin and advance therapeutic approaches to male infertility.