Altered microRNA expression profiles of human spermatozoa in normal fertile men of different ages.

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.

The Epidemiological Characteristics of Late-Onset Hypogonadism in Chinese Middle-Aged and Elderly Men: Two Cross-Sectional Studies in the Same Community.

The purpose of this study was to investigate the prevalence and epidemiological characteristics of late-onset hypogonadism (LOH) in middle-aged and elderly Chinese men. Two cross-sectional studies were conducted at 5-year intervals in community-dwelling men living in the same area. A total of 1472 (Study 1, S1) and 944 (Study 2, S2) men aged 40-69 years old were recruited as subjects. Subjects were evaluated through combining serum reproductive hormone levels with the Androgen Deficiency in Aging Males (ADAM) questionnaire and the Aging Males' Symptoms (AMS) scale. A significant difference was found in mean testosterone deficiency (TD) prevalence between S1 and S2, using either serum total testosterone (TT; 14.02% vs. 6.36%) or serum calculated free testosterone (cFT; 43.69% vs. 16.53%) cutoff values. According to the S1 or S2 data, the mean prevalence of LOH was 37.85%/15.47% in the positive ADAM test and 15.42%/9.43% in the positive AMS test (p < .01). According to classifications of TD based on gonadal status, the prevalence of secondary TD (27.34%) was higher than the primary (16.36%) and compensated (15.42%) TD in S1 (p < .01). However, there were significant differences among the prevalence of primary (6.89%), secondary (9.64%), and compensated (27.65%) TD in S2 (p < .05). Different types of testosterone levels, TD cutoff values, and questionnaires influenced the prevalence of TD and LOH. The serum FT cutoff value was an optimal threshold for evaluating and diagnosing TD and LOH, whose prevalence increased gradually with male aging.

The comparison of evaluative effectiveness between antral follicle count/age ratio and ovarian response prediction index for the ovarian reserve and response functions in infertile women.

Aim of the present study was to explore the evaluative effectiveness of age, ovarian volume (OV), antral follicle count (AFC), serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), AFC/Age ratio, AMH/Age ratio, FSH/luteinizing hormone (LH) ratio, and ovarian response prediction index (ORPI) to determine which could more advantageously assess ovarian reserve and response.This research enrolled 319 consecutive infertile women who had undergone in vitro fertilization-ET/intracytoplasmic sperm injection (IVF-ET/ICSI) treatments. Abovementioned variables were measured and calculated. Receiver operating characteristic (ROC) curve analysis was used to analyze the predictive accuracy of variables and to calculate cut-off values and corresponding sensitivity and specificity.Our study revealed that the significant variables for evaluating a decline in ovarian reserve include age, OV, FSH, AFC/Age ratio, AMH/Age ratio, and ORPI. Moreover, the area under the curve (AUC) of AFC/Age ratio was higher than other 5 variables (AUC = 1.000), and the cut-off value of AFC/Age ratio was 0.111 (sensitivity 100.00%, specificity 100.00%). The significant variables forecasting excessive ovarian response were age, AFC, AMH, FSH, AFC/Age ratio, AMH/Age ratio, FSH/LH ratio, and ORPI, and the significant variables forecasting poor ovarian response were AMH, LH, OV, AFC/Age ratio, AMH/Age ratio, and FSH/LH ratio. When ORPI was used to predict excessive response, the cut-off value of ORPI was 0.880 (sensitivity 84.72%, specificity 67.32%) and ORPI presented better effectiveness. When used to predict poor response, the evaluative effectiveness of 6 variables was almost similar, although the AUC of AFC/Age ratio presented the largest value.Regarding the infertile women, AFC/Age ratio performed better than did the other variables in evaluating ovarian reserve, and it offered excellent effectiveness in predicting poor ovarian response, however, ORPI presented better effectiveness in predicting excessive ovarian response.

Age-related changes in serum reproductive hormone levels and prevalence of androgen deficiency in Chinese community-dwelling middle-aged and aging men: Two cross-sectional studies in the same population.

To investigate the age-related nomograms and change trends of reproductive hormones, and prevalence of androgen deficiency (AD) in middle-aged and aging men from 2 studies.Two cross-sectional studies were conducted at 5-year intervals in Chinese community-dwelling men living in the same area. A total of 434 (Study 1, S1) and 944 (Study 2, S2) men aged 40 to 69 years were recruited as subjects and 59 (S1) and 98 (S2) men aged 20 to 39 years as controls to measure serum reproductive hormone levels.Serum total testosterone (TT) levels did not change significantly in S1, whereas TT levels increased in S2 with aging. Serum calculated free testosterone (cFT) levels gradually decreased with aging; however, only men aged 40 to 69 years showed this trend in S2. Serum luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels gradually increased, and serum testosterone secretion index (TSI) and free testosterone index (FTI) levels gradually decreased with male aging. The mean annual decrease values of serum cFT were 2.705 pmol/l in S1 and 1.060 pmol/l in S2. The cut-off values for AD in S1 and S2 were 9.13 nmol/l and 9.35 nmol/l for TT, and 169.00 pmol/l and 213.90 pmol/l for cFT. Using TT or cFT cut-off values, mean AD prevalence was 14.52% or 44.70% in S1, and 6.36% or 16.53% in S2. Based on cFT cut-off values, prevalence of AD increased gradually with male aging in a range of 25.30% to 61.63% in S1 and 1.20% to 23.03% in S2.The change patterns of serum LH, SHBG, TSI and FTI levels in middle-aged and aging males were consistent; however, there were differences in serum TT and cFT change patterns in S1 and S2 with male aging. cFT cut-off values were the optimal metric to evaluate AD, which can be present a ladder-like change in prevalence of different age groups.

[Levels of serum reproductive hormones and metabolic syndrome in adult males].

OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) and its relationship with reproductive hormones in adult males in China. METHODS: Using the cluster and stratified sampling methods, we conducted an investigation among 3 600 adult males aged over 20 years in Hebei, Shaanxi and Jiangsu provinces. We obtained their reproductive hormone levels, biochemical indicators and basic body indexes and compared them between the two groups of subjects. RESULTS: A total of 3 332 valid serum samples were collected, which revealed a prevalence rate of MS of 38.5% in the adult males. Compared with the non-MS subjects, the MS males showed a significantly higher free testosterone index (FTI, 0.39 ± 0.15 vs 0.45 ± 0.19, P < 0.01) but lower levels of total testosterone (TT, ï¼»16.35 ± 4.78ï¼½ vs ï¼»13.37 ± 4.23ï¼½ nmo/L, P < 0.01) and sex hormone-binding globulin (SHBG, ï¼»47.13 ± 20.50ï¼½ vs ï¼»33.32 ± 14.91ï¼½ nmol/L, P < 0.01) and testosterone secretion index (TSI, 3.64 ± 1.92 vs 3.14 ± 1.80, P < 0.01). There were no statistically significant differences between the two groups in the levels of calculated free testosterone (cFT) and LH (P > 0.05). Spearman rank correlation analysis showed that the levels of serum TT and SHBG were correlated with all the indicators of MS (P < 0.01) except systolic blood pressure (SBP), while that of cFT only with the levels of high-density lipoprotein (HDL), fasting blood glucose (FBG) and SBP (P < 0.01). After adjusted for age, smoking, drinking, and body mass index (BMI), all the MS indicators were significantly associated with the SHBG level (P < 0.01), but not high blood pressure with the serum TT level (P > 0.05). After adjusted for the age, smoking, drinking, BMI and TT, the serum SHBG level was the main independent risk factor for MS (OR: 0.965, 95% CI: 0.958－0.973, P < 0.01). CONCLUSIONS: The level of serum cFT is not correlated with while that of SHBG is the main independent risk factor for metabolic syndrome in adult males in China.

[Serum homocysteine and metabolic syndrome in middle-aged and elderly men].

OBJECTIVE: To investigate the relationship among serum reproductive hormone levels, serum homocysteine (Hcy) levels, metabolic syndrome (MS), and the components of MS in middle-aged and elderly males. METHODS: Using the cluster and stratified sampling methods and a unified structured questionnaire, we conducted a survey among 948 men aged 40 - 80 years in the rural community, measured their basic physical parameters, and obtained their reproductive hormone levels, serum Hcy concentrations, and metabolism-related indicators. We collected 868 valid questionnaires along with their serum samples, divided the subjects into an MS and a non-MS control group in a 1:1 ratio, and measured their serum Hcy concentrations. RESULTS: Among the subjects included, 132 were diagnosed with MS. Nonparametric tests showed statistically significant differences between the MS and non-MS groups in the waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P < 0.05), but not in age (P > 0.05). Significant differences were also observed between the two groups in the levels of serum tT, SHBG, LH, and FTI (P < 0.05) , but not in the concentrations of serum Hcy (P > 0.05). The concentration of serum Hcy exhibited no correlation with BMI, SBP, DBP, FBG, TG, and HDL-C (P > 0.05) and had no influence on MS. CONCLUSION: The concentration of serum Hcy is not significantly correlated with MS, nor with its components. The levels of male serum reproductive hormones are associated both with MS and with its components.

Is serum sex hormone-binding globulin a dominant risk factor for metabolic syndrome?

This multi-center, cross-sectional study investigated the association between serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels, and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG than those without MS (P < 0.001). There was no significant difference in serum free T (FT) levels between subjects with and without MS (P = 0.627). In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index (BMI), smoking and drinking status, and serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P< 0.01). However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status (OR 0.981, 95% CI 0.960-1.007). Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.