Formaldehyde Inhibits Sexual Behavior and Expression of Steroidogenic Enzymes in the Testes of Mice.

BACKGROUND: Formaldehyde, a ubiquitous environmental pollutant, is used extensively and has been proved to impair male reproduction in mammals. However, no trials have explored whether formaldehyde affects sexual function. AIM: To evaluate the effect of long-term formaldehyde exposure on sexual behavior and to investigate the potential mechanism. METHODS: Forty C57BL/6 male mice were randomly allocated to four equally sized groups. Mice were exposed to formaldehyde at a dose of 0 (control), 0.5, 5.0, or 10.0 mg/m3 by inhalation for 60 days. OUTCOMES: Sexual behavior, body and reproductive organ weights, testosterone concentration in serum and testicular tissue, expression of steroidogenic enzymes, quality of sperm, and testicular structure were measured. RESULTS: Formaldehyde inhibited sexual behavior and decreased reproductive organ weights in mice. Serum testosterone levels and intratesticular testosterone concentrations were decreased in the formaldehyde-treated groups. Expression levels of steroidogenic enzymes, including steroidogenic acute regulatory protein, cytochrome P450 cholesterol side-chain cleavage enzyme, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD), also were decreased in the testes of mice exposed to formaldehyde. Moreover, the structure of seminiferous tubules was destroyed and sperm quality decreased after formaldehyde exposure. In addition, the results indicated that the effects of formaldehyde were dose dependent. CLINICAL IMPLICATIONS: Efforts should be undertaken to decrease impairment of sexual function caused by formaldehyde exposure. STRENGTHS AND LIMITATIONS: The relatively small sample might have affected the outcomes. Further experiments are needed to study the mechanism of action of formaldehyde. CONCLUSION: Exposure to formaldehyde gas inhibited sexual behavior, caused reproductive organ atrophy, and impaired spermatogenesis in male mice, which might have been induced by suppressed expression of steroidogenic enzymes in Leydig cells and decreased testosterone synthesis. Zang Z-J, Fang Y-Q, Ji S-Y, et al. Formaldehyde Inhibits Sexual Behavior and Expression of Steroidogenic Enzymes in the Testes of Mice. J Sex Med 2017;14:1297-1306.

A herbal medicine, saikokaryukotsuboreito, improves serum testosterone levels and affects sexual behavior in old male mice.

Late-onset hypogonadism (LOH) is a clinical syndrome characterized with aging and declined serum testosterone levels. Sexual symptoms are also essential for the diagnosis of LOH. Testosterone replacement therapy is used widely to treat LOH. However, the side effects of it should not be ignored, such as fluid retention, hypertension and spermatogenic suppression. Therefore, alternate treatment modalities have been pursued. Herbal medicines used widely in China have achieved satisfying results with little side effects. Nonetheless, there are few pharmacological researches on them. In this study, 24-month-old mice were used as LOH animal models to explore the pharmacological effects of a herbal medicine, saikokaryukotsuboreito (SKRBT), on serum testosterone levels and sexual functions. Furthermore, the expression of steroidogenic acute regulatory (StAR) protein, a kind of rate-limiting enzyme of testosterone synthesis, was also examined. As a result, SKRBT improved the serum testosterone levels of these mice at a dose of 300 and 450 mg/kg. Multiple measures of sexual behavior were enhanced. The expression of StAR was also increased. Therefore, this study suggested that SKRBT can improve the serum testosterone levels by activating the expression of StAR and might be a viable option to treat sexual symptoms caused by LOH.

Anti-fibrotic effects via regulation of transcription factor Sp1 on hepatic stellate cells.

BACKGROUND: Hepatic stellate cells (HSCs), the central cells in hepatic fibrosis, are characterized by sustaining activation, a process that consists in increased proliferation and over-expression of fibrotic genes. Transcription factor Sp1 mediates the expression of a variety of fibrotic genes expression and thereby play an important role in fibrosis. In addition, previous reports have indicated that Sp1 binding activity is greatly increased in activated HSCs. Thus, our aim was to investigate the anti-proliferative and anti-fibrotic effects of the oligonuceotide decoy of the transcription factor Sp1, ODN, a potent inhibitor of Sp1-activated transcription. METHODS: We optimized Lipofectamin 2000 (LF2000):ODN DNA ratio for the transfection of hepatic stellate cells HSC-T6. Then we measure the effect of transfected ODN on HSC-T6 cells' proliferation and fibrotic gene expression, and study the mechanism involved. RESULTS: At a DNA concentration of 1 µM and a ratio ODN DNA:LF2000 of 1:3, HSC-T6 cells have the maximal transfection efficiency with the lowest toxicity. Transfected ODN effectively blocks Sp1 binding to the promoter regions of cell cycle regulatory proteins cyclin D1, p27(KIP1) and fibrotic genes, including transforming growth factor (TGF)-ß1, Platelet-derived growth factor (PDGF)-BB, α-SMA, α1 (I) collagen and tissue inhibitor of metalloproteinases-1 (TIMP-1). ODN inhibits HSC-T6 proliferation and fibrotic genes expression in vitro. CONCLUSION: Sp1 is a key transcription factor that mediates proliferation and fibrotic gene synthesis of HSC-T6, inhibition of Sp1 with decoy ODN may be an effective approach to prevent the progression of hepatic fibrosis.

Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice.

BACKGROUND: Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. METHODS: Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed. RESULTS: In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 ± 12.31 ng/g vs. 74.10 ± 11.45 ng/g, P = 0.027; sperm number: [14.94 ± 4.63] × 106 cells/ml vs. [8.79 ± 4.38] × 106 cells/ml, P = 0.002; sperm motility: 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 ± 11.01 ng/ml vs. 49.30 ± 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 ± 0.09 vs. 0.84 ± 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 ± 8.67, P = 0.005; sperm number: [4.34 ± 2.45] × 106 cells/ml, P = 0.018; sperm motility: 19.53 ± 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 ± 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 ± 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 ± 0.09, P < 0.001), and fertility was also suppressed (P < 0.05, respectively). CONCLUSION: SKRBT had no adverse effect on fertility potential in aging male mice.

Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice.

Twenty-four-month-old male C57BL/6 mice with low serum testosterone levels were used as a late-onset hypogonadism (LOH) animal model for examining the effects of velvet antler polypeptide (VAP) on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day (n = 10 mice per dose). Control animals (n = 10) received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone (ITT) concentration also increased in the VAP-treated groups. The expression of StAR, P450scc, and 3ß-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis (StAR, P450scc, and 3ß-HSD) and the following promotion of testosterone synthesis in vivo.

Predictive factors and unfavourable prognostic factors of interstitial lung disease in patients with polymyositis or dermatomyositis: a retrospective study.

BACKGROUND: Interstitial lung disease (ILD) is a serious lung complication in polymyositis (PM) and dermatomyositis (DM) which affects prognosis and requires a more aggressive approach in therapy. This study investigated the prevalence, characteristics, predictive factors and unfavourable prognostic factors of ILD in newly diagnosed PM, DM and amyopathic DM (ADM). METHODS: From January 2000 to December 2008, the medical records of 197 consecutive PM and DM patients at the Second Affiliated Hospital of Sun Yat-Sen University were reviewed excluding overlapping, juvenile, and malignancy-associated cases. The patients were assigned to an ILD (69 patients) and a non-ILD group (128 patients). The clinical features, laboratory findings, and prognosis were compared. RESULTS: The multivariate analysis indicated that older age at onset (OR 1.033, 95%CI 1.009 - 1.058, P = 0.007), fever (OR 4.109, 95%CI 1.926 - 8.767, P < 0.001) and arthritis/arthralgia (OR 2.274, 95%CI 1.101 - 4.695, P = 0.026) were the independent predictive factors for developing ILD in PM/DM after excluding anti-Jo-1. Regarding anti-Jo-1, fever (OR 4.912, 95%CI 2.121 - 11.376, P < 0.001) was associated with ILD. Poor survival in ILD patients was associated with ILD clinical subset (RR 0.122, 95%CI 0.049 - 0.399, P < 0.001), ADM/DM/PM-ILD (RR 0.140, 95%CI 0.031 - 0.476, P = 0.002), cardiac involvement (RR 4.654, 95%CI 1.391 - 15.577, P = 0.013) and serum albumin level (RR 0.910, 95%CI 0.831 - 0.997, P = 0.042). CONCLUSIONS: Patients who presented with fever tended to have a higher frequency of PM/DM-associated ILD. A Hamman-Rich-like presentation, ADM-ILD, cardiac involvement and hypoalbuminemia were poor prognostic factors in ILD-PM/DM.