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Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

ABSTRACT: Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR p<0.05). Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

SUBMITTER: Allaway D

PROVIDER: S-EPMC5152928 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Male infertility has become a global health problem. Currently, the diagnosis of male infertility depends on the results of semen quality or requires invasive surgical intervention. The process is complex and time-consuming. Metabolomics is an emerging platform with unique advantages in disease diagnosis and pathological mechanism research. In this study, ultra-performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry (UPLC-ESI-IT-TOFMS) combined with chemometrics methods was used to discover potential biomarkers of male infertility based on non-targeted plasma metabolomics. Plasma samples from healthy controls (HC, n = 43) and various types of infertile patients, i.e., patients having oligozoospermia (OS, n = 36), asthenospermia (AS, n = 56) and erectile dysfunction (ED, n = 45) were analyzed by UPLC-ESI-IT-TOFMS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed. The results of OPLS-DA showed that HCs could be discriminated from infertile patients including OS (R 2 = 0.903, Q 2 = 0.617, AUC = 0.992), AS (R 2 = 0.985, Q 2 = 0.658, AUC = 0.999) or ED (R 2 = 0.942, Q 2 = 0.500, AUC = 0.998). Some potential biomarkers were successfully discovered by variable selection methods and variable important in the projection (VIP) in combination with the T-test. Statistical significance was set at p < 0.05; the Benjamini-Hochberg false discovery rate was used to reduce type 1 errors resulting from multiple comparisons. The identified biomarkers were associated with energy consumption, hormone regulation and antioxidant defenses in spermatogenesis. To elucidate the pathophysiology of male infertility, relative metabolic pathways were studied. It was found that male infertility is closely related to disturbed phospholipid metabolism, amino acid metabolism, steroid hormone biosynthesis metabolism, metabolism of fatty acids and products of carnitine acylation, and purine and pyrimidine metabolisms. Plasma metabolomics provides a novel strategy for the diagnosis of male infertility and offers a new insight to study pathogenesis mechanism.

Project description:ImportanceDespite similar sexual activity rates among male and female adolescents, males are more likely to have their first sexual intercourse before age 13 years. The developmental needs and pathways to healthy trajectories for young males remain unknown.ObjectiveTo examine the prevalence of sexual intercourse before age 13 years among male adolescents; the variation by race/ethnicity, location, and maternal educational level; and the wantedness of this first sexual experience.Design, setting, and participantsThis cross-sectional analysis was conducted from September 2017 to June 2018, using pooled 2011, 2013, and 2015 data from the school-based Youth Risk Behavior Surveillance System (YRBSS) and the 2006 to 2015 data of males aged 15 to 24 years from the household-based National Survey of Family Growth (NSFG). The percentage of males reporting sexual onset before age 13 years was estimated using survey-weighted logistic regression to test for differences by race/ethnicity within each national survey and within metropolitan areas (for YRBSS, high school and middle school samples). Among NSFG survey respondents, differences in wantedness of first sexual intercourse by age at first sexual intercourse were examined, along with the associations between sexual initiation and socioeconomic covariates.Main outcomes and measuresSexual onset before age 13 years.ResultsData from a total of 19 916 male high school students (from YRBSS) and 7739 males aged 15 to 24 years (from NSFG) were included in the analysis. The sample was largely composed of non-Hispanic white males: 8789 (57.1%) from the YRBSS and 3737 (58.0%) from the NSFG. Sexual onset before age 13 years was reported nationally by 7.6% (95% CI, 6.8%-8.4%) of male high school students and 3.6% (95% CI, 3.0%-4.2%) of males aged 15 to 24 years. The proportion of male students who reported having sexual intercourse before age 13 years varied across metropolitan sites, from 5% (95% CI, 4%-7%) in San Francisco, California, to 25% (95% CI, 23%-28%) in Memphis, Tennessee, with elevated rates among non-Hispanic black and Hispanic males in most metropolitan areas. In the NSFG data set, respondents whose mothers had a college degree or higher educational level were statistically significantly less likely (OR, 0.31; 95% CI, 0.19-0.49) to report having sexual intercourse before age 13 years compared with those whose mothers did not have a college degree. Among males who reported having their first sexual experience before age 13 years, 8.5% (95% CI, 3.8%-17.8%) described their first sexual intercourse as unwanted.Conclusions and relevanceRates of sexual onset before age 13 years among young males varied by race/ethnicity, location, and maternal educational level, presenting important implications for the provision of early, inclusive, and comprehensive sex education and sexual and reproductive health care to male children and adolescents.

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Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

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