In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.
Animals ; Dihydrotestosterone ; blood ; Epidermal Growth Factor ; blood ; Male ; Medicine, Tibetan Traditional ; Mice ; Plant Extracts ; pharmacology ; Prostatic Hyperplasia ; chemically induced ; drug therapy ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Testosterone Propionate ; Urticaceae ; chemistry

Anti-Müllerian hormone (AMH) is a functional marker of fetal Sertoli cells. The germ cell number in adults depends on the number of Sertoli cells produced during perinatal development. Recently, AMH has received increasing attention in research of disorders related to male fertility. This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders. We have determined that follicle-stimulating hormone (FSH) promotes AMH transcription in the absence of androgen signaling. Testosterone inhibits the transcriptional activation of AMH. The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue, for example, that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis. The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Müllerian duct syndrome (PMDS), combined with clinical manifestations. The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development (DSD). Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells. Serum AMH levels are varying in patients with male fertility-related disorders, including pubertal delay, severe congenital hypogonadotropic hypogonadism, nonobstructive azoospermia, Klinefelter syndrome, varicocele, McCune-Albright syndrome, and male senescence.
Anti-Mullerian Hormone/metabolism* ; Follicle Stimulating Hormone/blood* ; Gene Expression Regulation ; Humans ; Infertility, Male/blood* ; Male ; Testosterone/blood*

In this study, we investigated the genetics, clinical features, and therapeutic approach of 14 patients with 5α-reductase deficiency in China. Genotyping analysis was performed by direct sequencing of PCR products of the steroid 5α-reductase type 2 gene (SRD5A2). The 5α-reductase activities of three novel mutations were investigated by mutagenesis and an in vitro transfection assay. Most patients presented with a microphallus, variable degrees of hypospadias, and cryptorchidism. Eight of 14 patients (57.1%) were initially reared as females and changed their social gender from female to male after puberty. Nine mutations were identified in the 14 patients. p.G203S, p.Q6X, and p.R227Q were the most prevalent mutations. Three mutations (p.K35N, p.H162P, and p.Y136X) have not been reported previously. The nonsense mutation p.Y136X abolished enzymatic activity, whereas p.K35N and p.H162P retained partial enzymatic activity. Topical administration of dihydrotestosterone during infancy or early childhood combined with hypospadia repair surgery had good therapeutic results. In conclusion, we expand the mutation profile of SRD5A2 in the Chinese population. A rational clinical approach to this disorder requires early and accurate diagnosis, especially genetic diagnosis.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Adolescent ; Adult ; Asian People/genetics* ; Child ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY/genetics* ; Follicle Stimulating Hormone/blood* ; Genitalia, Male/abnormalities* ; Humans ; Hypospadias/genetics* ; Luteinizing Hormone/blood* ; Male ; Membrane Proteins/genetics* ; Mutation/genetics* ; Sequence Alignment ; Steroid Metabolism, Inborn Errors/genetics* ; Testosterone/blood* ; Young Adult

ObjectiveTo explore the antagonistic effect of vitamin E (VE) on male reproductive toxicity induced by di-2-ethylhexyl phthalate (DEHP) in pubertal SD rats and its underlying mechanisms.

METHODSThirty 5-week-old male SD rats were randomly divided into five groups of equal number, corn oil control, low-dose (10 mg/kg/d), medium-dose (100 mg/kg/d) and high-dose DEHP exposure (500 mg/kg/d), and VE intervention (high-dose DEHP + VE ［100 mg/kg/d］), and treated respectively for 30 successive days. At 3 days after treatment, the testes of the animals were harvested for determination of the oxidative stress index, serum reproductive hormone levels, cauda epididymal sperm parameters, and expressions of cell apoptosis-related genes and proteins.

RESULTSCompared with the control group, the rats of the medium- and high-dose DEHP groups showed significant decreases in the levels of such serum reproductive hormones as follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T), sperm parameters as average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), straightness (STR), linearity (LIN) and wobble (WOB), and the activities of superoxide dismutase (SOD) and glutathione peroxide (GSH-Px), but significant increases were observed in the latter two groups in the content of malondialdehyde (MDA)(［3.32±0.87］ nmol/mg pro vs ［2.13±0.49］ nmol/ mg pro), mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio, and protein expressions of Cytochrome C and Caspase-3. In comparison with the high-dose DEHP group, the VE intervention group exhibited remarkably increased serum LH and T levels, sperm VAP, VSL, VCL, STR and WOB, and activities of SOD and GSH-Px, but markedly decreased mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio as well as the protein expressions of Cytochrome C and Caspase-3 in the testis tissue (P<0.05).

CONCLUSIONSExposure to DEHP induces androgen secretion disorders, causes oxidative damage to the testicular tissue, activates the mitochondrial apoptosis pathway in the testis, and ultimately reduces the quality of epididymal sperm, while VE can protect the rat testis from DEHP-induced reproductive toxicity.

Animals ; Antioxidants ; pharmacology ; Apoptosis ; genetics ; Autophagy-Related Protein 5 ; metabolism ; Caspase 3 ; metabolism ; Diethylhexyl Phthalate ; antagonists & inhibitors ; Epididymis ; Follicle Stimulating Hormone ; blood ; Luteinizing Hormone ; blood ; Male ; Malondialdehyde ; metabolism ; Mitochondria ; drug effects ; Oxidative Stress ; drug effects ; Oxidoreductases ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; Spermatozoa ; drug effects ; physiology ; Superoxide Dismutase ; metabolism ; Testis ; drug effects ; Testosterone ; blood ; Vitamin E ; pharmacology

ObjectiveTo investigate the correlation of the levels of reproductive hormones and oxidative stress in the seminal plasma with semen parameters in obese males.

METHODSBased on the body mass index (BMI), we divided 138 infertile men into three groups: normal (BMI <24 kg/m2, n = 48), overweight (24 kg/m2≤BMI<28 kg/m2, n = 47), and obesity (BMI ≥28 kg/m2, n = 43). We determined the concentrations of follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL), testosterone (T) and estradiol (E2) in the serum by electrochemiluminescence and measured the levels of superoxide dismutase (SOD), glutathione-S-transferases (GSTs), reactive oxygen species (ROS) and malondialdehyde (MDA) in the seminal plasma by ELISA, compared the above indexes among the three groups, and analyzed their correlation with the semen volume, sperm concentration, total sperm count, and percentage of progressively motile sperm (PMS).

RESULTSThe semen volume was significantly lower in the obesity than in the normal group (［2.63 ± 0.74］ vs ［3.37 ± 1.00］ ml, P < 0.05), and so was the percentage of PMS in the overweight and even lower in the obesity than in the normal group (［47.91 ± 12.89］ and ［41.27 ± 15.77］ vs ［54.04 ± 13.29］%, P < 0.05). Compared with the normal group, both the overweight and obesity groups showed markedly decreased levels of serum T (［4.83 ± 1.42］ vs ［3.71 ± 1.22］ and ［3.49 ± 1.12］ ng/ml, P<0.05), T/LH ratio (1.53 ± 0.57 vs 1.19 ± 0.54 and 0.97 ± 0.51, P<0.05), SOD (［112.05 ± 10.54］ vs ［105.85 ± 6.93］ and ［99.33 ± 8.39］ U/ml, P<0.05), and GSTs (［31.75±6.03］ vs ［29.54±5.78］ and ［29.02±4.52］ U/L, P<0.05), but remarkably increased seminal plasma ROS (［549.93±82.41］ vs ［620.61±96.13］ and ［701.47±110.60］ IU/ml, P<0.05) and MDA (［7.46 ± 2.13］ vs ［8.72 ± 1.89］ and ［10.47 ± 2.10］ nmol/L, P<0.05). BMI was correlated positively with ROS and MDA, but negatively with the semen volume, PMS, T, T/LH, SOD and GSTs (P<0.05); LH negatively with sperm concentration, total sperm count and GSTs (P<0.05); PRL negatively GSTs (P<0.05); E2 positively with SOD (P<0.05); T positively with SOD (P<0.05) but negatively with MDA (P<0.05); T/LH positively with PMS and SOD (P<0.05) but negatively with ROS and MDA (P<0.05); SOD positively with semen volume, PMS and GSTs (P<0.05) but negatively with ROS and MDA (P<0.05); GSTs negatively with sperm concentration; total sperm count and MDA (P<0.05); ROS positively with MDA (P<0.01) but negatively with PMS (P<0.05); and MDA negatively with semen volume (P<0.05). Multivariate logistic regression analysis showed that the independent factors influencing the semen volume were BMI and GSTs, those influencing the total sperm count were BMI and T, and those influencing PMS were BMI and MDA.

CONCLUSIONSIncreased BMI induces changes in the levels of male reproductive hormones and seminal plasma oxidative stress and affects semen quality, which may be associated with male infertility.

Body Mass Index ; Estradiol ; blood ; Follicle Stimulating Hormone ; blood ; Humans ; Infertility, Male ; blood ; classification ; metabolism ; Luteinizing Hormone ; blood ; Male ; Malondialdehyde ; analysis ; Obesity ; blood ; metabolism ; Oxidative Stress ; Prolactin ; blood ; Reactive Oxygen Species ; analysis ; Reproduction ; Semen ; metabolism ; Semen Analysis ; Sperm Count ; Testosterone ; blood

ObjectiveTo investigate the relationship of the levels of serum androgens with lipid metabolism in middle-aged and elderly men in Zunyi, Guizhou.

METHODSUsing the stratified cluster sampling method, we conducted a questionnaire investigation and physical examinations among 437 men in Zunyi City. We divided the subjects into a middle-aged (40－64 ［53.20 ± 7.41］ years, n = 269) and an elderly group (=≥65 ［70.63 ± 4.66］ years, n = 168) and collected fasting elbow venous blood samples from them for measuring the levels of total testosterone (TT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), total cholesterol (TCH), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), calculated free testosterone (cFT), free testosterone index (FTI), and testosterone secretion index (TSI).

RESULTSCompared with the elderly group, the middle-aged males showed significantly lower SHBG, LH, HDL and LDL, and higher cFT, FTI, TSI, TG and TCH (all P < 0.05). TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, while cFT was positively correlated with TCH, and so was FTI with TG, TCH with LDL, and TSI with TCH, HDL and LDL (all P < 0.05), but LH was negatively correlated with TG, TCH and LDL (all P < 0.05). Multivariate linear regression analysis showed that TT and SHBG were negatively correlated with TG, TCH, HDL and LDL, and so was LH with TCH, HDL and LDL (all P < 0.05).

CONCLUSIONSIn the middle-aged and elderly men in Zunyi, low concentrations of TT, SHBG and LH were associated with the increased risk of high-TCH and -LDL dyslipidemia, low concentrations of TT and SHBG with that of high-TG dyslipidemia, while high concentrations of TT, SHBG and LH with that of low-HDL dyslipidemia.

Adult ; Aged ; Androgens ; blood ; China ; Cholesterol ; blood ; Dyslipidemias ; etiology ; Humans ; Lipid Metabolism ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Luteinizing Hormone ; Male ; Middle Aged ; Multivariate Analysis ; Sex Hormone-Binding Globulin ; Testosterone ; blood ; Triglycerides ; blood

OBJECTIVE: To study the effect of 6-week intensive training on renal function in rats and the mechanism of exercise-induced proteinuria. METHODS: Thirty-six male SD rats, aged 6 weeks, were divided into two groups, including a control group(C,=12)and an overtraining group(M,=24). After the rats adapted to feeding for 4 d, group C did not carry out any exercise, and the M group did 6-week of increasing load swimming, 6 days a week, once a day. Started with the load of 1%weight at the beginning of the 4 week,and gradually increased (to 6% weight). Took a single urine from both groups 30 min after the end of the training. Blood was taken from the main ventral vein, and the bilateral kidneys were to be tested. The levels of tested urine protein, microalbumin and neutrophil gelatinase associated lipocalin(NGAL) was determined by using enzyme linked immunosorbent assaytest. The content of urine creatinine was tested with alkaline picric acid method,. The serum levels of colorimetric method to determine serum creatinine and urea nitrogen were determined by colorimetric method. The expression of Nephrin in renal tissue was detected by Western blot and the radioimmunoassay was used to test serum testosterone, corticosterone and renin-angiotensin system related index. RESULTS: Compared with group C, the serum testosterone/cortisone(T/C) of group M was decreased significantly (<0.01). The urine total protein(TP), microalbumin (mAlb), microalbumin/creatinine (mAlb/CRE), NGAL, blood urea nitrogen (BUN) and serum creatinine(SCr) were increased significantly (<0.01). The abnormality of glomerular structure was obvious, and the paller scores were higher. The protein expression of Nephrin was obviously down decreased (<0.01). The renin activity (Ra) and angiotension Ⅱ (Ang Ⅱ) in renal and circulating blood were decreased significantly (<0.01). CONCLUSIONS The effects of 6-week intensive training on renal function in rats and the mechanism of exercise-induced proteinuria may be that overtraining can induce the continuous excitation of Reninrenin activity in renal and circulating blood, down-regulated the expression of Nephrin, lead to abnormality of renal structure and function, and proteinuria.
Animals ; Blood Urea Nitrogen ; Corticosterone ; blood ; Creatinine ; blood ; Kidney ; physiopathology ; Male ; Membrane Proteins ; metabolism ; Physical Conditioning, Animal ; adverse effects ; Proteinuria ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System ; Testosterone ; blood

Stress affects the male reproductive system and can cause sub-fertility or infertility. Although Phyllanthus emblica L. (PE) extract has been shown to have high antioxidant capacity and protective properties in damaged tissue, the preventive effects of PE extract on testicular function from stress-related impairment have never been demonstrated. This study aimed to investigate the effects of PE aqueous leaf extract on testicular impairment and protein marker changes in rats suffering from chronic stress. Adult male rats were divided into four groups: a control group, a chronic stress (CS) group, and two groups with CS that received different doses of PE extract (50 or 100 mg/kg body weight (BW)). In the treatment groups, the animals were given PE extract daily before stress induction for 42 consecutive days. Stress was induced through immobilization (4 h/d) followed by forced cold swimming (15 min/d). Sperm quality and the histology of the testes and caudal epididymis were examined, as were levels of serum corticosterone, testosterone, and malondialdehyde (MDA). The expressions of testicular steroidogenic acute regulatory (StAR) and tyrosine-phosphorylated proteins were investigated using immuno-Western blot analysis, as these proteins are assumed to play important roles in spermatogenesis and androgen synthesis. The results showed that PE (50 mg/kg BW) significantly increased sperm concentration and testosterone levels, while decreasing corticosterone levels, MDA levels, sperm head abnormalities, and acrosome-reacted sperm in CS rats. In addition, PE at both doses was found to diminish testicular histopathology in the CS rats. We also found that 50 mg/kg BW of PE significantly improved StAR protein expression and altered the intensities of some tyrosine-phosphorylated proteins in testis. We conclude that PE leaf extract at 50 mg/kg BW can prevent testicular damage in rats with CS.
Acrosome Reaction ; Animals ; Antioxidants/pharmacology* ; Corticosterone/blood* ; Epididymis/metabolism* ; Male ; Malondialdehyde/blood* ; Phosphoproteins/metabolism* ; Phosphorylation ; Phyllanthus emblica/chemistry* ; Plant Extracts/pharmacology* ; Plant Leaves/chemistry* ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Spermatogenesis/drug effects* ; Spermatozoa/drug effects* ; Stress, Physiological ; Testis/drug effects* ; Testosterone/blood* ; Tyrosine/chemistry*

Objective: To investigate whether androgens can regulate the expression of eNOS in rat corpus cavernosum through AKT3, PIK3CA, CALM, and CAV1 and influence erectile function. METHODS: Thirty-six 8-week-old male SD rats were randomly divided into groups A (4-week control), B (6-week control), C (4-week castration), D (6-week castration), E (4-week castration + testosterone replacement), and F (6-week castration + testosterone replacement). Both the testis and epididymis were removed from the rats in groups C, D, E and F, and on the second day after surgery, the animals of groups E and F were subcutaneously injected with testosterone propionate at 3 mg per kg of the body weight qd alt while all the others with isodose oil instead. At 4 weeks (for groups A, C and E) and 6 weeks (for groups B, D and F) after treatment, we detected the maximum intracavernous pressure (ICPmax), the mean carotid arterial pressure (MAP) and their ratio (ICPmax/MAP), measured the level of serum testosterone (T), and determined the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 in the corpus cavernosum by Western blot and immunohistochemistry. RESULTS: No statistically significant differences were observed in the body weight and MAP among different groups. The serum T level and ICPmax/MAP were remarkably lower in groups C and D than in the other four groups (P<0.01) as well as in groups E and F than in A and B (P<0.05) but exhibited no significant differences either between E and F or between A and B. Immunohistochemistry showed that eNOS and P-eNOS were mainly expressed in the vascular endothelial cell membrane and cavernous vascular lumen, while AKT3, PIK3CA, CALM and CAV1 chiefly in the vascular endothelial cell cytoplasm and membrane, with a few in the smooth muscle cells. Western blot analysis manifested that the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 were markedly lower in groups C and D than in A, B, E and F (P<0.01) as well as in D than in C (P<0.05) but those in groups E and F did not showed any significant difference from those in A and B, nor E from F or A from B. CONCLUSIONS Androgens can improve erectile function by upregulating the expressions of AKT3, PIK3CA, CALM and CAV1 protein molecules and activating eNOS after its phosphorylation, though the exact molecular mechanisms are yet to be further studied.
Animals ; Blood Pressure ; Blotting, Western ; Caveolin 1 ; metabolism ; Class I Phosphatidylinositol 3-Kinases ; metabolism ; Erectile Dysfunction ; Hormone Replacement Therapy ; Male ; Monomeric Clathrin Assembly Proteins ; metabolism ; Myocytes, Smooth Muscle ; Nitric Oxide Synthase Type III ; metabolism ; Orchiectomy ; Penile Erection ; physiology ; Penis ; enzymology ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Testosterone Propionate ; administration & dosage

Objective: To investigate the influence of different procedures of testicular sperm retrieval on the levels of serum inhibin B (INHB), antisperm antibodies (AsAb), follicle-stimulating hormone (FSH), and testosterone (T) in patients with azoospermia. METHODS: We randomly assigned 210 azoospermia patients to receive testicular sperm extraction (TESE, n = 50), testicular sperm aspiration (TESA, n = 56), testicular fine needle aspiration (TEFNA, n = 64), or microscopic TESE (micro-TESE, n = 40). We measured the levels of serum INHB, FSH, and T and the positive rate of AsAb before and at 1 and 3 months after surgery. RESULTS: Compared with the baseline, the levels of serum FSH at 1 and 3 months after surgery showed no statistically significant differences in the TESE (［8.51 ± 4.34］ vs ［8.76 ± 3.07］ and ［7.24 ± 3.32］ IU/L, P >0.05), TESA (［7.70 ± 2.72］ vs ［7.90 ± 4.57］ and ［8.04 ± 3.65］ IU/L, P >0.05), TEFNA (［6.04 ± 3.17］ vs ［6.08 ± 2.70］ and ［6.10 ± 3.32］ IU/L, P >0.05), or micro-TESE group (［6.59 ± 2.74］ vs ［6.89 ± 1.78］ and ［6.75 ± 2.57］ IU/L, P >0.05); the positive rate of AsAb (IgM) was significantly increased at 1 month in the TESE (0.00 vs 14.00%, P <0.05) and micro-TESE groups (2.50% vs 15.00%, P <0.05), while the serum T level markedly decreased in the two groups (［16.52 ± 6.25］ vs ［9.25 ± 5.76］ nmol/L and ［14.16 ± 5.45］ vs ［8.23 ± 4.12］ nmol/L, P <0.05); the levels of serum INHB were remarkably reduced at 1 and 3 months in the TESE (［70.56 ± 23.17］ vs ［42.63 ± 15.34］ and ［44.05 ± 18.47］ pg/ml, P <0.05), TESA (［68.71 ± 14.74］ vs ［40.55 ± 20.51］ and ［42.11 ± 19.34］ pg/ml, P <0.05), TEFNA (［76.81 ± 27.04］ vs ［46.31 ± 19.28］ and ［48.32 ± 20.54］ pg/ml, P <0.05), and micro-TESE groups (［74.74 ± 28.35］ vs ［45.27 ± 18.83］ and ［47.64 ± 28.34］ pg/ml, P <0.05), but with no statistically significant differences among the four groups (P >0.05). CONCLUSIONS Different procedures of testicular sperm retrieval have different impacts on the testicular function and AsAb in patients with azoospermia.
Antibodies ; blood ; Azoospermia ; blood ; physiopathology ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; blood ; Male ; Sperm Retrieval ; Spermatozoa ; immunology ; Testis ; metabolism ; physiopathology ; Testosterone ; blood