[Show abstract][Hide abstract] ABSTRACT: The d-galactose (d-gal)-injected animal model, which is typically established by administering consecutive subcutaneous d-gal injections to animals for approximately six or eight weeks, has been frequently used for aging research. In addition, this animal model has been demonstrated to accelerate aging in the brain, kidneys, liver and blood cells. However, studies on aging in male reproductive organs that have used this animal model remain few. Therefore, the current study aimed to optimize a model of male reproductive aging by administering d-gal injections to male mice and to determine the possible mechanism expediting senescence processes during spermatogenesis. In this study, C57Bl/6 mice were randomized into five groups (each containing 8-10 mice according to the daily intraperitoneal injection of vehicle control or 100 or 200 mg/kg dosages of d-gal for a period of six or eight weeks). First, mice subjected to d-gal injections for six or eight weeks demonstrated considerably decreased superoxide dismutase activity in the serum and testis lysates compared to those in the control group. The lipid peroxidation in testis also increased in the d-gal-injected groups. Furthermore, the d-gal-injected groups exhibited a decreased ratio of testis weight/body weight and sperm count compared to the control group. The percentages of both immotile sperm and abnormal sperm increased considerably in the d-gal-injected groups compared to those of the control group. To determine the genes influenced by the d-gal injection during murine spermatogenesis, a c-DNA microarray was conducted to compare testicular RNA samples between the treated groups and the control group. The d-gal-injected groups exhibited RNA transcripts of nine spermatogenesis-related genes (Cycl2, Hk1, Pltp, Utp3, Cabyr, Zpbp2, Speer2, Csnka2ip and Katnb1) that were up- or down-regulated by at least two-fold compared to the control group. Several of these genes are critical for forming sperm-head morphologies or maintaining nuclear integration (e.g., cylicin, basic protein of sperm head cytoskeleton 2 (Cylc2), casein kinase 2, alpha prime interacting protein (Csnka2ip) and katanin p80 (WD40-containing) subunit B1 (Katnb1)). These results indicate that d-gal-injected mice are suitable for investigating male reproductive aging.
Preview · Article · Jan 2016 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: Male infertility affects approximately 50% of all infertile couples. The male-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile or immature sperm, and sperm with structural defects such as those caused by premature chromosomal condensation and DNA damage. Our previous studies based on a knockout mice model indicated that SEPT12 proteins are critical for the terminal morphological formation of sperm. SEPT12 mutations in men result in teratozospermia and oligozospermia. In addition, the spermatozoa exhibit morphological defects of the head and tail, premature chromosomal condensation, and nuclear damage. However, the molecular functions of SEPT12 during spermatogenesis remain unclear. To determine the molecular functions of SEPT12, we applied a yeast 2-hybrid system to identify SEPT12 interactors. Seven proteins that interact with SEPT12 were identified: SEPT family proteins (SEPT4 and SEPT6), nuclear or nuclear membrane proteins (protamine 2, sperm-associated antigen 4, and NDC1 transmembrane nucleoproine), and sperm-related structural proteins (pericentriolar material 1 and obscurin-like 1). Sperm-associated antigen 4 (SPAG4; also known as SUN4) belongs to the SUN family of proteins and acts as a linker protein between nucleoskeleton and cytoskeleton proteins and localizes in the nuclear membrane. We determined that SEPT12 interacts with SPAG4 in a male germ cell line through coimmunoprecipitation. During human spermiogenesis, SEPT12 is colocalized with SPAG4 near the nuclear periphery in round spermatids and in the centrosome region in elongating spermatids. Furthermore, we observed that SEPT12/SPAG4/LAMINB1 formed complexes and were coexpressed in the nuclear periphery of round spermatids. In addition, mutated SEPT12, which was screened from an infertile man, affected the integration of these nuclear envelope complexes through coimmunoprecipitation. This was the first study that suggested that SEPT proteins link to the SUN/LAMIN complexes during the formation of nuclear envelopes and are involved in the development of postmeiotic germ cells.
[Show abstract][Hide abstract] ABSTRACT: The history of alternative medicine is perhaps as long as the history of human medicine. The development of evidence-based medicine has not annihilated alternative medicine. On the contrary, more people turn to alternative medicine because this approach to treatment serves as an effective remedial or supportive treatment when used in conjunction with evidence-based medicine. In contemporary healthcare, alternative medicine is now an essential part of integrated medicine. In Taiwan, most professional medical practitioners have not received proper education about alternative medicine and therefore generally lack comprehensive knowledge on this subject. While alternative medicine may be effective when used with some patients, it may also impart a placebo effect, which helps restore the body and soul of the patients. Medical staff with advanced knowledge of alternative medicine may not only help patients but also improve the doctor-patient relationship. There is great diversity in alternative medicine, with some alternative therapies supported by evidence and covered by insurance. However, there also remain fraudulent medical practices that may be harmful to health. Medical staff must be properly educated so that they can provide patients and their family a proper understanding and attitude toward alternative medicine. Therefore, alternative medicine should be included in the standard medical education curriculum. Offering classes on alternative medicine in university for more than 10 years, the author shares his experiences regarding potential content, lecture subjects, group experience exercises, and in-class activities. This article is intended to provide a reference to professors in university medical education and offer a possible model for alternative medicine education in Taiwan.
No preview · Article · Dec 2014 · Hu li za zhi The journal of nursing
[Show abstract][Hide abstract] ABSTRACT: Objective
To assess the associated risk factors and the prevalence of urinary incontinence (UI) among women with hypertension (H/T) aged 60 or over in Taiwan.
Materials and Methods
A total of 2410 women aged 60 or over were selected by a multistage random sampling method and a total of 1519 women completed the face-to-face interviews. Only women who answered “yes” to the question “Do you have H/T?” were included in the H/T sample. The factors were assessed by frequency and Pearson's χ2 test using a significance level of p < 0.05. Logistic regression was used to investigate the significance of dichotomous dependent variables.
A total of 39.7% (602 women) interviewees had H/T, among which 39.9% (240 women) had UI symptoms. The prevalence of UI among women aged 60 or over with or without H/T was significantly different (p = 0.006). Risk factors were age [odds ratio (OR) = 1.043, 95% confidence interval (CI) 1.016–1.071, per year], diabetes mellitus (DM) (OR = 1.653, 95% CI 1.105–2.474), previous urinary diseases (OR = 3.462, 95% CI 2.260–5.301), and body mass index (BMI; OR = 1.060, 95% CI 1.012–1.110, per unit). There was no significant association between UI and drug allergy, smoking, hysterectomy, hormone therapy, or gynecological surgery.
UI can be a frequent and annoying problem for aged women. In women with H/T, UI is significantly related to risk factors such as age, DM, BMI, and urinary diseases. In addition, BMI is considered a key risk factor for H/T. Therefore, effective control of BMI would help in controlling H/T and UI in aged women.
Full-text · Article · Jun 2014 · Taiwanese Journal of Obstetrics and Gynecology
[Show abstract][Hide abstract] ABSTRACT: The septin gene belongs to a highly conserved family of polymerizing GTP-binding cytoskeletal proteins. SEPTs perform cytoskeletal remodeling, cell polarity, mitosis, and vesicle trafficking by interacting with various cytoskeletons. Our previous studies have indicated that SEPTIN12+/+/+/- chimeras with a SEPTIN12 mutant allele were infertile. Spermatozoa from the vas deferens of chimeric mice indicated an abnormal sperm morphology, decreased sperm count, and immotile sperm. Mutations and genetic variants of SEPTIN12 in infertility cases also caused oligozoospermia and teratozoospermia. We suggest that a loss of SEPT12 affects the biological function of microtublin functions and causes spermiogenesis defects. In the cell model, SEPT12 interacts with α- and β-tubulins by co-immunoprecipitation (co-IP). To determine the precise localization and interactions between SEPT12 and α- and β-tubulins in vivo, we created SEPTIN12-transgene mice. We demonstrate how SEPT12 interacts and co-localizes with α- and β-tubulins during spermiogenesis in these mice. By using shRNA, the loss of SEPT12 transcripts disrupts α- and β-tubulin organization. In addition, losing or decreasing SEPT12 disturbs the morphogenesis of sperm heads and the elongation of sperm tails, the steps of which are coordinated and constructed by α- and β-tubulins, in SEPTIN12+/+/+/- chimeras. In this study, we discovered that the SEPTIN12-microtubule complexes are critical for sperm formation during spermiogenesis.
Full-text · Article · Nov 2013 · International Journal of Molecular Sciences
[Show abstract][Hide abstract] ABSTRACT: Objective:
To show the flexibility in magnetic resonance imaging (MRI) of seminal vesicle (SV) and intra-abdominal segment of vas deferens for the patients with congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of vas deferens (CUAVD).
Fourteen consecutive patients with CAVD had transrectal ultrasonography (TRUS) and further MRI evaluations. TRUS was performed using a 7.5-MHz transducer, and images of the SVs were obtained, calculated in the transaxial plane. MRI studies were performed with a 1.5-7 superconducting system, T1- and T2-weighted axial, coronal, and sagittal imaging of the pelvis was obtained. If the SVs were present, then their size was measured for the morphologic classification and diagnosis. All of the patients also received cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation testing.
In a series of 12 men with CBAVD, only 4 were found to have bilateral SV agenesis using MRI. The remaining 8 men with unilateral hypoplasia still had SV remnants. MRI also detected the intra-abdominal segment of the vas deferens. Through our study of MRI, SV agenesis is not well associated with the presence of CFTR mutation in patients with CAVD.
MRI provides a precise imaginal diagnosis of SV defect, which is superior to the TRUS examination for the patients with CAVD. Compared with the previous inaccurate examination method of TRUS, this study demonstrates that MRI can provide better images for the patients with CAVD for the clinical diagnosis of existing defects of internal seminal tract and internal organs.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Asthenozoospermia is a major cause of male infertility. However, the molecular mechanisms underlying sperm-motility defects remain largely unknown in the majority of cases. In our previous study, we applied a proteomic approach to identify unknown proteins that were downregulated in spermatozoa with low motility compared to spermatozoa with good motility. Several sperm motility- related proteins have been identified. In this study, 3-hydroxyisobutyrate dehydrogenase (HIBADH), one of the proteins identified using the proteomic tools, is further characterized.
Reverse-transcription polymerase chain reactions (RT-PCR), western blotting, and immunofluorescence assays (IFA) were preformed to investigate the expression pattern. The enzymatic activity of HIBADH was evaluated in sperm with good (>50 %), moderate (< 50 %) and lower motility (< 20 %).
Using RT-PCR, we found that transcripts of HIBADH are enriched in the cerebellum, heart, skeletal muscle, uterus, placenta, and testes of male humans. In western blotting, it is expressed in the placenta, testes, and spermatozoa. During spermiogenesis, HIBADH is located at the mid-piece (a specialized development from the mitochondria) of elongating, elongated, and mature sperm. The enzymatic activity of HIBADH in sperm with moderate and lower motility were significantly reduced compared with good motility (P<0.0001 and P<0.05, respectively).
Our study indicated that HIBADH is involved in the mitochondrial function of spermatozoa, and maintains sperm motility. It may serve as a sperm-motility marker.
Full-text · Article · Feb 2013 · Journal of Assisted Reproduction and Genetics
[Show abstract][Hide abstract] ABSTRACT: XX male is a rare sex chromosomal disorder in infertile men. The purpose of this study was to distinguish the clinical and genetic features of the 46,XX male syndrome from other more frequent, testicular-origin azoospermic causes of male infertility.
To study 46,XX male syndrome, we compared clinical and endocrinological parameters to other groups with testicular-origin azoospermia, and to an age-matched group of healthy males and females as normal control. Fluorescent in situ hybridization for detection and localization of the sex-determining region of the Y gene (SRY), array-based comparative genomic hybridization screening, and real-time qualitative polymerase chain reaction of FGF9, WT1, NR5A1, and SPRY2 genes were performed in this genetic investigation.
Our three patients with 46,XX male syndrome had a much higher follicular-stimulating hormone level, lower body height, lower testosterone level, and ambiguous external genitalia. One of the three patients with 46,XX male syndrome was SRY-negative. A further genetic study, including a comparative genomic hybridization array and real-time polymerase chain reaction, showed a gain of FGF9 copy numbers only in the SRY-negative 46,XX male. The genetic copy number of the FGF9 gene was duplicated in that case compared to the normal female control and was significantly lower than that of the normal male control. No such genomic gain was observed in the case of the two SRY-positive 46,XX males.
Similar to clinical manifestations of 46,XX male syndrome, genetic evidence in this study suggests that FGF9 may contribute to sex reversal, but additional confirmation with more cases is still needed.
No preview · Article · Feb 2013 · Journal of the Formosan Medical Association
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy of hydrodistention (HD) followed by bladder training (BT) versus HD alone in patients with interstitial cystitis (IC).
A total of 70 patients with IC were included and randomly assigned to two groups: one treated with HD (HD group) and the other treated with HD plus BT (HD plus BT group). Each patient was followed up using a weekly diary for 8 weeks after HD and monthly thereafter for 6 months after HD. Evaluation parameters included age, duration of IC in years, how many doctors visited before treatment, urgency, bladder pain, daytime voided volume per void, nocturnal volume per void, daytime voids per day, and nocturia per day.
Age, duration of IC in years, doctors visited before treatment, and voiding profiles of patients before treatments between the two groups did not show statistical significance. However, at 24 weeks after HD, the proportions of urgency, and bladder pain of the HD group versus the HD plus BT group were 43.48% versus 10.71% (p = 0.008), and 34.78% versus 14.29% (p = 0.086), respectively. Concurrently, the mean ± standard deviation of daytime voided volume per void, nocturnal volume per void, daytime voids per day, and nocturia per day of the HD group and HD plus BT group are 212.2 ± 114.2 mL and 300.1 ± 90.2 mL (p = 0.005), 276.8 ± 113.0 mL and 360.0 ± 129.6 mL (p = 0.018), 8.2 ± 3.2 and 6.2 ± 1.4 (p = 0.010), and 2.2 ± 1.2 and 1.5 ± 0.7 (p = 0.019), respectively.
HD followed by BT produced a statistically significantly better effect than HD alone in the treatment of patients with IC.
No preview · Article · Dec 2012 · Taiwanese journal of obstetrics & gynecology
[Show abstract][Hide abstract] ABSTRACT: Interstitial cystitis (IC) has been described as a chronic debilitating sterile inflammatory multifactorial bladder syndrome of unknown etiology. IC is characterized by bladder pain (or suprapubic pain) associated with urgency, urinary frequency, and nocturia. Because the pathogenesis of IC remains unclear, it is still an enigma and represents a diagnostic and therapeutic challenge. The diagnosis of IC remains unclear and is based on exclusion of other diseases. Consequently, IC has usually been underdiagnosed, and the consensus on best available treatment for the disease is lacking. The current goal for the treatment of IC is usually symptomatic relief, and treatment protocols are based on empiricism. Multiple forms of therapy are available, and most patients can be managed conservatively. Nevertheless, the efficacy of most treatments is short term. This review article gives an overview of the available treatments for IC.
No preview · Article · Dec 2012 · Taiwanese journal of obstetrics & gynecology
[Show abstract][Hide abstract] ABSTRACT: Introduction. Neurogenic erectile dysfunction resulting from cavernous nerve (CN) injury is a major complication caused by radical prostatectomy. The use of platelet-rich plasma (PRP) on the nerve-injured site has shown promising results for the nerve regeneration. However, the effects of PRP injection in corpus cavernosum after bilateral CN injury have never been investigated.
Aim. To assess the neuroprotective effect of PRP injection in corpus cavernosum after bilateral CN injury.
Methods. Male Sprague-Dawley rats were randomly divided into three groups: Group I underwent sham operation, while the remaining two groups underwent bilateral CN crush. Crush injury groups were treated at the time of injury with an application of PRP or normal saline only injection in the corpus cavernosum, respectively. Four weeks later, erectile function (EF) was assessed by CN electrosimulation, and CNs as well as penile tissue were collected for histology.
Main Outcome Measures. Intracavernous pressure (ICP) monitored during electrical stimulation of CNs; myelinated axons number of CNs and dorsal penile nerve; collagen type change, number of apoptotic cells, and mRNA expression of caspase-3 and transforming growth factor-β1 (TGF-β1) in the corpus cavernosum.
Results. Four weeks after surgery, in the vehicle-only group, the functional evaluation showed a lower mean maximal ICP than that in the sham group (P < 0.05). PRP treatments resulted in significant recovery of EF, as compared with the vehicle-only group (P < 0.05). Histologically, the PRP-treated group had a significant preservation of myelinated axons of CNs compared with the vehicle-only group (P < 0.05) and reduced the apoptotic index. The mRNA expression of TGF-β1 in the corpus cavernosum tissue was significantly decreased in the PRP group compared with the vehicle-only group (P < 0.05).
Conclusions. PRP injection in the corpus cavernosum increased the number of myelinated axons and facilitated recovery of EF in the bilateral CN injury rat model. Wu C-C, Wu Y-N, Ho H-O, Chen K-C, Sheu M-T, and Chiang H-S. The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med 2012;9:2838–2848.
Full-text · Article · Aug 2012 · Journal of Sexual Medicine
[Show abstract][Hide abstract] ABSTRACT: Umbilical cord blood is rich in primitive natural killer (NK) cells, which are activated by interleukin (IL)-12. It was previously reported that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated in maternal serum during normal pregnancy. Thus, we compared the immune regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord blood and adult peripheral blood.
After stimulation with IL-27, IL-12, and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by blood mononuclear cells was performed. Then immunofluorescence staining, reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the effects of IL-27 and IL-12 in isolated NK cells.
IL-27, IL-12, and IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood cells and cord blood cells, but the proliferation of distinct subpopulations of cells was not evident. Similar results were also obtained with purified cord blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce aggregation and morphological changes of umbilical cord blood cells. Finally, IL-27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1) transcripts in purified cord blood NK cells. However, the activation of signal transducer and activator of transcription 3 (STAT3) in NK cells was only detected in the presence of IL-27, but not IL-12 alone.
From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12.
No preview · Article · May 2012 · Journal of the Formosan Medical Association
[Show abstract][Hide abstract] ABSTRACT: Endothelial cells contribute to the function and integrity of the vascular wall, and a functional aberration may lead to atherogenesis. There is increasing evidence on the atheroprotective role of androgens. Therefore, we studied the effect of the androgens-testosterone and dihydrotestosterone-and estradiol on human coronary artery endothelial cell (HCAEC) function. We found by MTT assay that testosterone is not cytotoxic and enhances HCAEC proliferation. The effect of testosterone (10-50 nM), dihydrotestosterone (5-50 nM), and estradiol (0.1-0.4 nM) on the adhesion of tumor necrosis factor-α (TNF-α)-stimulated HCAECs was determined at different time points (12-96 h) by assessing their binding with human monocytic THP-1 cells. In addition, the expression of adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1), was determined by ELISA and Western blot analysis. Both testosterone and dihydrotestosterone attenuated cell adhesion and the expression of VCAM-1 and ICAM-1 in a dose- and time-dependent manner. Furthermore, androgen treatment for a longer duration inhibited cell migration, as demonstrated by wound-healing assay, and promoted tube formation on a Matrigel. Western blot analysis demonstrated that the expression of phosphorylated endothelial nitric oxide synthase (eNOS) increased, whereas that of inducible nitric oxide synthase (iNOS) decreased following the 96-h steroid treatment of TNF-α-stimulated HCAECs. Our findings suggest that androgens modulate endothelial cell functions by suppressing the inflammatory process and enhancing wound-healing and regenerative angiogenesis, possibly through an androgen receptor (AR)-dependent mechanism.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
Low sex hormone-binding globulin (SHBG) is associated with metabolic syndrome (MetS), but its relationship with inflammation is unclear.
This cross-sectional study included 696 subjects (255 men, 235 pre-menopausal women, and 206 postmenopausal women). Body mass index, waist circumference, blood pressure, lipid profiles, plasma glucose, insulin, FSH, LH, total testosterone (TT), estradiol, SHBG, dehydroepiandrosterone sulfate (DHEA-S), and hs-CRP concentrations were measured. MetS was defined according to the updated National Cholesterol Education Program criteria with modification of waist circumference for Asians.
Serum hs-CRP and SHBG were negatively correlated in men (r=-0.29, p<0.001), pre-menopausal women (r=-0.38, p<0.001), and postmenopausal women (r=-0.27, p<0.001). In men, TT and hs-CRP showed a negative association (r=-0.25, p<0.001), but the association was attenuated after adjusting for SHBG (r=-0.14, p=0.039). Multivariate regression models showed that SHBG was independently associated with hs-CRP in men (r=-0.18, p=0.009), pre-menopausal women (r=-0.15, p=0.025), and postmenopausal women (r=-0.21, p=0.005), adjusted for age, MetS components, insulin resistance, low-density lipoprotein-cholesterol, and serum sex hormone levels.
Serum SHBG and hs-CRP concentrations were inversely correlated in men, pre-menoposal, and post-menopausal women independently.