Puberty and adolescence are periods of brain-driven physiological development that display increased incidences of depression development. Adolescents display significant alterations to their stress response signaling, sleep patterns, and metabolism when compared to pre-pubescents. Increased exposure to stress, sleep disturbances, and impaired energy acquisition is typical during puberty and adolescence and similarly increases the likelihood of developing depression. A promising avenue of limiting the deleterious effects of stress and sleep disruption on pubertal and adolescent depressive behaviour is the use of treatments that blunt underlying metabolic impairments associated with depression. Treatments that directly or indirectly increase availability of the glucose metabolite L-lactate are associated with depression reduction. The investigations included in this dissertation evaluate the usability of L-lactate treatments in reducing depression development in pubertal CD-1 male and female mice. This work first examines a previously proposed oral lactate solution, its effect on energy substrate concentration and drowsiness, and its efficacy as a safe oral L-lactate treatment (Chapter 2). Subsequent research aimed to identify a pubertal model of depression that would allow future testing of L-lactate antidepressant treatment. Pubertal male and female mice exposed to chronic sleep disruption were evaluated for stress reactivity and depressive behavior and were identified as a model for antidepressant testing (Chapter 3). In the final study, we evaluated the effects of chronic sleep disruption on the expression of energy metabolites like L-lactate and glucose within the brain, its effect on neurotransmitters associated with depression, and changes to sleep architecture in relation to depression behaviour. Sleep disrupted and depressed animal models were administered L-lactate producing probiotics and were evaluated for improvements to energy substrate concentration, neurotransmitter expression, sleep recovery, and depression reduction (Chapter 4). The present thesis provides groundwork for the use of L-lactate therapies in depressed pubertal and adolescent groups and provides initial evaluations of probiotic intervention as a prevention strategy for juvenile depression.

Objectives: To analyze the association between age at menarche, as a measure of sexual maturation, and adult height from ten published studies. Methods: Compared published measurements of age at menarche, adult height, and within-sample relationships observed in ten studies, for women from several societies and socioeconomic backgrounds, living in the 20th century, Results: In these studies, early maturers were taller during pre-puberty, but had shorter adult height then later maturers. Late maturers experience a longer period of pre-pubertal growth and a delayed age of peak height velocity, leading to an extended overall time of growth, until adult stature was obtained. Conclusions: Improved living conditions and energy balance increase childhood growth rate, and are associated with an earlier puberty, and shorter duration of growth. In developed countries duration of growth may play an increasingly important role in adult stature.

Previous research has shown an inverse relationship between age and the relative intensity at which ventilatory threshold (VT) occurs in adolescent boys. However, no study has examined the effect of maturity status on VT in the differences in boys from the onset of puberty, adolescents. The purpose of this study was to compare VT among adolescent boys of different maturational groups. Methods: For this study, moderately active adolescent male participants (14 ± 3 y) completed this study. Maturational status of the participants was determined via years from peak height velocity (PHV), which is an estimation of somatic maturity status derived from age, standing height, seated height, body mass, and leg length. Participants were categorized into PRE- (lesser than 1 year till PHV), PERI- (within 1 year of PHV), and POST-PHV (greater than 1 year past PHV). All participants completed a ramp graded exercise test on a cycle ergometer. During the test, participants were given a three-minute warm-up with no resistance before starting at a workload of 30 watts which increased at a rate of 1 watt every 3 seconds until volitional fatigue. Throughout the test, oxygen consumption (VO2) and ventilation were measured. VT was determined, as a percentage of VO2max, from the ventilation versus VO2 graph using the maximal deviation method. Differences in VT between maturational groups were examined using one-way ANOVA. Results: A significant (F=5.36; p=0.014) difference in VT among maturational groups was found (Appendix A, Figure 2). Post hoc analysis revealed that PRE (p=0.029) and PERI (p=0.009) had VT occur at a significantly greater relative percentage of VO2max than POST. However, no significant (p=0.970) differences were found between PRE and PERI (Appendix A, Figure 3). Conclusion: Adolescent males in PRE and PERI demonstrated higher VT as a percentage of their VO2max compared to POST. This finding suggests the differences in the delayed switch from aerobic to anaerobic metabolism during incremental exercise in adolescent boys who are PRE and PERI.

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Raising beef females in drylots is gaining popularity because a more intensive management style facilitates adequate feeding for growth. However, drylots increase stocking density which has previously been shown to be stressful and impair reproductive development, whereas exercise has been shown to alleviate stress. Therefore, the objective was to determine if providing access to an exercise area would improve reproductive development of replacement beef heifers reared in drylots. Body weight, pedometer readings, and blood samples for plasma cortisol were collected weekly. Additional blood samples for genes associated with welfare, hair cortisol samples, and heifer temperament was assessed periodically throughout the trial. The results illustrate that providing heifers reared in drylots with high stocking density does not result in similar physiological or reproductive responses as heifers reared on traditional pasture. Thus, research is warranted investigating the impact of scheduled exercise on the reproductive development and welfare of drylot raised heifers.

Yes / There are few reliable osteological indicators to detect parity or infer puberty in skeletal remains. Nitrogen (δ15N) and stable carbon (δ13C) isotope ratios in human tissues can be affected by metabolically unbalanced states engendered by pregnancy or rapid growth, offering potential biomarkers. This pilot study explores the potential of incremental dentine-collagen isotope ratio analysis to identify puberty and gestation. Methodology: Incremental dentine δ15N and δ13C profiles were produced by analysing third molars extracted as part of dental treatment of 10 individuals living in Sudan. Demographic and anthropometric data at the time of tooth extraction was available. Medical histories were unknown. Results: Isotopic signatures potentially related to pubertal growth, with an average δ15N reduction of 0.78±0.29‰, are indicated. Six isotopic signals suggestive of pregnancy, with an average δ15N decrease of 0.48±0.22‰, are also observed. The timing, speed and amplitude of post-partum δ15N patterns seemingly infer infant feeding practices and maternal nutritional status. Conclusion: This pilot study highlights the potential of incremental dentine isotope analysis for the reconstruction of early reproductive histories in skeletal remains. However, controlled studies with larger human cohort are needed to validate these findings, establish isotopic signals linked to puberty and lactation, and improve chronology accuracy.

Some early puberty girls engage in high-risk externalizing behaviors such as early sexual activity, delinquent behavior, and disruptive behaviors. Harsh parenting experienced by girls who develop early has been associated with delinquent and disruptive behaviors. The purpose of this quantitative correlational study was to examine predictive relationships between the style of parental discipline by mothers of early puberty girls and the likelihood and frequency of the girls' engagement in high-risk behaviors. Parenting style theory, including the authoritarian, authoritative, and permissive style of parenting, served as the theoretical foundation for the study. Survey data were collected from 28 mothers who identified as having a daughter who experienced early puberty. The Parenting Scale subscales were used to measure the dysfunctional parenting behaviors of laxness, overreactivity, and verbosity. Logistic regression analysis revealed no statistically significant relationships between the early puberty girl's involvement in risky behaviors and dysfunctional parenting. Results may be used by human service and public health officials to increase awareness of early puberty and to promote public health policies to address the individual, social, and economic implications of early puberty in girls.

A idade normal para início da puberdade em meninas varia bastante, de 8 a 13 anos, e os genes envolvidos nesse controle são parcialmente conhecidos. Fatores ambientais, como alimentação e exposição a disruptores endócrinos, contribuem para essa variabilidade, de modo que genes modulados epigeneticamente podem justificar parte da complexidade desse processo. O termo epigenética se refere às modificações na expressão gênica que não são causadas por alterações na sequência do DNA. A metilação do DNA é o mecanismo epigenético mais bem estudado. Na última década surgiram evidências demonstrando a relação entre metilação do DNA e desenvolvimento puberal. Em fêmeas de roedores, a hipermetilação do DNA levou à puberdade precoce. Em humanos, a puberdade precoce central (PPC) familial causada por mutações nos genes MKRN3 e DLK1 é considerada um defeito do imprinting, fenômeno epigenético no qual apenas um dos alelos parentais é expresso, estando o outro metilado e inativo. Além disso, um conceito atual propõe que o início da puberdade requer a repressão epigenética de fatores inibidores do eixo gonadotrófico. Recentemente, genes zinc finger (ZNF) foram relacionados ao processo puberal, e muitos deles codificam repressores transcricionais. Neste trabalho, estudamos a metilação do DNA do sangue periférico de 10 pacientes do sexo feminino com PPC familial (casos índices) e 33 meninas com desenvolvimento puberal normal (15 pré-púberes e 18 púberes), usando a plataforma Human Methylation 450 BeadChip. Duas pacientes tinham PPC de causa genética (uma com mutação no MKRN3 e outra com deleção no DLK1) e oito tinham PPC idiopática, sem mutações identificadas pelo sequenciamento exômico global. Cento e vinte regiões diferencialmente metiladas foram identificadas entre as meninas saudáveis pré-púberes e púberes, estando 74% delas no cromossomo X. Apenas uma região mostrou-se hipometilada no grupo púbere e, de maneira importante, contém a região promotora do ZFP57, fator necessário para manutenção do imprinting. Uma vez que a hipermetilação nas regiões promotoras dos genes é relacionada à inibição transcricional, o achado de hipermetilação global do DNA na puberdade sugere que haja inibição de fatores inibidores do eixo gonadotrófico, o que resultaria no início do processo puberal. O receptor estrogênico destacou-se como um fator transcricional que se liga a sete genes diferencialmente metilados entre os controles pré-púberes e púberes. As pacientes com PPC apresentaram mais sítios CpG hipermetilados tanto na comparação com as meninas pré-púberes (81%) quanto púberes (89%). Há doze genes ZNF contendo sítios CpG hipermetilados na PPC. Não foram encontradas anormalidades de metilação nos genes MKRN3 e DLK1 nem em suas regiões regulatórias. Em conclusão, este estudo evidenciou hipermetilação global do DNA em meninas com puberdade normal e precoce, sugerindo que esse padrão é uma marca epigenética da puberdade. Pela primeira vez, mudanças no metiloma de pacientes com PPC foram descritas. Modificações na metilação de vários genes ZNF parecem compor a complexa rede de mecanismos que leva ao início da puberdade humana / Normal puberty initiation varies greatly among girls, from 8 to 13 years, and the genetic basis for its control is partially known. Environmental factors, such as nutrition and exposure to endocrine disruptors, contribute to this variance, and epigenetically modulated genes may justify some of the complexity observed in this process. Epigenetics refers to alterations in gene expression that are not caused by changes in DNA sequence itself. DNA methylation is the best studied epigenetic mechanism. In the last decade, evidence has emerged showing the relationship between DNA methylation and pubertal development. In female mice, DNA hypermethylation led to precocious puberty. In humans, familial central precocious puberty (CPP) caused by mutations in the MKRN3 and DLK1 genes is considered a disorder of imprinting, an epigenetic phenomenon in which only one parental allele is expressed, and the other allele is methylated and inactive. In addition, animal studies indicated that pubertal timing requires epigenetic repression of inhibitory factors of the gonadotrophic axis. Recently, zinc finger genes (ZNF) were related to pubertal development, many of which encode transcriptional repressors. In the present study, we analyzed the DNA methylation of peripheral blood samples from 10 female patients with familial CPP (index cases) and 33 girls with normal pubertal development (15 pre-pubertal and 18 pubertal), using the Human Methylation 450 BeadChip assay. Genetic CPP was diagnosed in two patients (one with a MKRN3 mutation and the other with a DLK1 deletion). The remaining eight cases with idiopathic CPP were previously evaluated by whole exome sequencing and no causative mutations were identified so far. We evidenced 120 differentially methylated regions between pre-pubertal and pubertal healthy girls, and 74% of them were located at the X chromosome. Only one genomic region was hypomethylated in the pubertal group. Of note, it contains the promoter region of ZFP57, an important factor for imprinting maintenance. As DNA hypermethylation in gene promoters is related to gene silencing, the finding of global DNA hypermethylation in puberty suggests inhibition of inhibitory factors of the hypothalamic-pituitary-gonadal axis that results in puberty onset. Importantly, the estrogen receptor was identified as a transcriptional factor that binds to seven differentially methylated genes associated with pubertal process. Patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Twelve ZNF genes were recognized as having hypermethylated CpG sites in CPP. The methylation analyses of MKRN3 and DLK1 genes showed no abnormalities. In conclusion, this study revealed a widespread DNA hypermethylation in girls with normal and precocious puberty, suggesting that this pattern can be an epigenetic signature of puberty. For the first time, changes in the methylome of patients with CPP were described. We highlight that alterations in methylation levels of several ZNF genes may impact the onset of human puberty