Since the 1980s, research has linked environmental factors to adult-onset diseases. The DOHaD theory suggests that exposures during development can permanently affect organ function, predisposing individuals to adult diseases. Studies indicate that protein restriction or a high-fat diet (HFD) during this phase impacts adult metabolism since programmed dysfunctions may depend on changes established during puberty, such as the reproductive system. However, there are no studies on the impact of low-protein (LP) or HFD on male testicles during this phase. For this, Male Wistar rats were categorized into three dietary groups: LP (isocaloric low-protein pelletized); HFD; and Control (balanced commercial) until PND 60. This study was approved by the CEUA-UEM. On postnatal day 61, the animals were euthanized for histopathological, sperm count, and oxidative stress assessments in the testis and epididymis. Statistical analyses were conducted following established ethical principles in animal research. The research revealed significant alterations in daily sperm production and transit through the epididymis. Sperm morphology was affected in the experimental groups. Mitochondrial activity increased in the HFD group. Testicular and epididymal histopathology, seminiferous tubule diameter, and germinal epithelium height, as well as the number of Sertoli and Leydig cells, remained unchanged. Stereological analysis revealed tissue remodeling in the epididymis, particularly in the LP group. LP group showed an increase in lipid peroxidation in the oxidative damage test. In conclusion, low-protein and HFD during peripubertal age did not affect postnatal testicular development in rats. However, they impacted sperm quality, potentially affecting fertility and male reproductive system development.

Guided by concepts from life history (LH) theory, a large human research literature has tested the hypothesis that exposures to extrinsic mortality (EM) promote the development of faster LH strategies (e.g., earlier/faster reproduction, higher offspring number). A competing model proposes that, because EM in the past was intimately linked to energetic constraints, such exposures specifically led to the development of slower LH strategies. We empirically address this debate by examining (1) LH variation among small-scale societies under different environmental conditions; (2) country-, regional- and community-level correlations between ecological conditions, mortality, maturational timing, and fertility; (3) individual-level correlations between this same set of factors; and (4) natural experiments leveraging the impact of externally-caused changes in mortality on LH traits. Partially supporting each model, we found that harsh conditions encompassing energetic stress and ambient cues to EM (external cues received through sensory systems) have countervailing effects on the development of LH strategies, both delaying pubertal maturation and promoting an accelerated pace of reproduction and higher offspring number. We conclude that, although energetics are fundamental to many developmental processes, providing a first tier of environmental influence, this first tier alone cannot explain these countervailing effects. An important second tier of environmental influence is afforded by ambient cues to EM. We advance a 2-tiered model that delineates this second tier and its central role in regulating development of LH strategies. Consideration of the first and second tier together is necessary to account for the observed countervailing shifts toward both slower and faster LH traits.

This editorial describes the Cass Review findings and the extraordinary challenge we all face in managing uncertainty amid a toxic and highly polarised debate. Children and young people will only get the best care if patients and professionals join forces to seek answers collaboratively and respectfully.

Limited analyses based on national samples have assessed whether early attention-deficit/hyperactivity disorder (ADHD) symptoms predict later internalizing and externalizing symptoms in youth and the influence of sex and pubertal timing on subsequent psychiatric symptoms. This study analyzed data (n = 2818) from the Environmental influences on Child Health Outcomes Program national cohort. Analyses used data from early childhood (mean age = 5.3 years) utilizing parent-reported ADHD symptoms to predict rates of internalizing and externalizing symptoms from late childhood/adolescence (mean age = 11.9 years). Within a subsample age at peak height velocity (APHV) acted as a proxy to assess pubertal timing from early childhood (mean age = 5.4 years) to adolescence (mean age = 12.3 years). Early-childhood ADHD symptoms predicted later psychiatric symptoms, including anxiety, depression, aggressive behavior, conduct problems, oppositional defiant disorder, and rule-breaking behavior. Earlier APHV was associated with increased Conduct Disorder symptoms from late childhood to adolescence for females only. A stronger relation between ADHD symptoms and later aggression was observed in females with earlier APHV, whereas this same pattern with aggression, conduct problems and depression was observed in males with later APHV. Clinicians should consider that both young girls and boys with elevated ADHD symptoms, particularly with off-set pubertal timing, may be at risk for later psychiatric symptoms.

The aim of this study was to evaluate whether high-fat (HF) diet intake during puberty can program obesity as well as generate glucose imbalance and hepatic metabolic dysfunctions in adult life. Male Wistar rats were randomly assigned into two groups: rats fed standard chow (NF) and rats fed a HF from postnatal 30-day-old (PND30) until PND60. Then, both groups were fed a standard chow from PND60 until PND120. Euthanasia and samples collections occurred at PND120. HF animals were overweight (+11%) and had increased adiposity, hyperphagia (+12%), hyperglycaemia (+13%), hyperinsulinemia (+69%), and hypertriglyceridemia (+34%). Plasma glucose levels during intravenous glucose tolerance test (ivGTT) and intraperitoneal insulin tolerance test (ipITT) were also higher in the HF group, whereas Kitt was significantly lower (–34%), suggesting reduced insulin sensitivity. In the same sense, HF animals present pancreatic islets hypertrophy and high β-cell mass. HF animals also had a significant increase in blood glucose levels during pyruvate tolerance test, indicating increased gluconeogenesis. Hepatic morphology analyses showed an increase in lipid inclusion in the HF group. Moreover, PEPCK and FAS protein expression were higher in the livers of the HF animals (+79% and + 37%, respectively). In conclusion, HF during puberty causes obese phenotype leading to glucose dyshomeostasis and nonalcoholic fatty liver disease, which can be related to the overexpression of proteins PEPCK and FAS.

Studies found support for a link between pubertal timing and self-regulation in low-resource environments. This link could potentially explain a link between pubertal timing and early risk behavior. This study builds on this body of research by examining the mediated effect of pubertal timing on sexual activity through self-regulation in 728 adolescents and their families in a group with poor resources and a group with adequate resources. Income-to-Needs (ITN) was measured at age 7.5 to establish two groups (low-ITN and Medium/High-ITN). Pubertal timing was measured at age 10.5, self-regulation was assessed at age 14 and operationalized with effortful control, and sexual activity was assessed at age 16. Structural equation modeling was employed to test the hypothesized model in both groups. The link between pubertal timing and sexual activity mediated by effortful control was only significant in the low-ITN group. Specifically, more advanced pubertal maturity was associated with lower levels of adolescents’ effortful control, which in turn was associated with more sexual activity at age 16. Findings were partially replicated with a drug use index replacing sexual activity. This study shows a different operating link from pubertal timing to effortful control and subsequent risk behavior in resource-poor environments. Implications are discussed.

Increasing age and puberty affect the hypothalamic pituitary adrenal (HPA) axis maturation, which is likely associated with an increase in environmental demands (e.g., social) and vulnerability for the onset of psychiatric conditions (e.g., depression). There is limited research as to whether such patterns are consonant in youth with autism spectrum disorder (ASD), a condition marked by social challenges, dysregulation of the HPA axis, and higher rates of depression setting the stage for enhanced vulnerability during this developmental period.

The current study interrogated diurnal cortisol by examining (1) cortisol expression longitudinally over the pubertal transition between autistic and neurotypical youth, (2) the trajectory of diurnal cortisol and the unique contributions of age vs. puberty, and (3) potential sex differences. As hypothesized, results indicate autistic compared to typically developing youth demonstrate a shallower diurnal slope and elevated evening cortisol. These differences were in the context of higher cortisol and flatter rhythms based on age and pubertal development. Also, sex-based differences emerged such that females in both groups had higher cortisol, flatter slopes, and higher evening cortisol than males. The results show that despite the trait-like stability of diurnal cortisol, HPA maturation is impacted by age, puberty, sex, as well as an ASD diagnosis.

Induction of puberty in cattle breeds that attain puberty in later stages, such as Gir, allows the earlier beginning of reproductive life and it might increase oocyte quality. Here, the ovulatory capacity of prepuberal Gir heifers was studied and its relationship to follicular growth, luteinizing hormone (LH) secretion and oocyte quality was evaluated. Peripubertal Gir heifers were treated with a progesterone-based protocol and according to ovulatory response were separated into groups: not-ovulated (N-OV) and ovulated (OV). Serial blood samples were taken 24 h after estradiol treatment on day 12 to evaluate LH secretion. Cumulus–oocyte complexes (COCs) were collected using ovum pick-up and assessed for brilliant cresyl blue (BCB) staining rate, IVF-grade oocytes rate, and mean oocyte diameter, in comparison with cow oocytes. Gene expression of developmental competence markers (ZAR1, MATER, and IGF2R) was also analyzed. The largest follicle diameters were similar between N-OV and OV groups on the day of estradiol treatment (d12) and the next day and decreased (P = 0.04) in the N-OV group thereafter. LH pulse secretion was different between groups (N-OV = 3.61 ± 0.34 vs OV = 2.83 ± 0.21 ng/ ml; P = 0.04). COC assessment showed that the number of recovered oocytes, BCB+ rate, IVF-grade oocytes and oocyte size was similar (P > 0.05) among groups, resembling adult cow patterns. ZAR1, MATER and IGF2R gene expression in oocytes were also similar (P > 0.05) in N-OV and OV groups. In conclusion, our results demonstrate a lower LH secretion profile in peripubertal Gir heifers prone to ovulate after induction protocol, and that oocyte quality is not affected on a short-term basis by ovulation itself.

Female adolescents have a greatly increased risk of depression starting at puberty, which continues throughout the reproductive lifespan. Sex hormone fluctuation has been highlighted as a key proximal precipitating factor in the development of mood disorders tied to reproductive events; however, hormone-induced affective state change is poorly understood in the pubertal transition. The present study investigated the impact of recent stressful life events on the relationship between sex hormone change and affective symptoms in peripubertal female participants. Thirty-five peripubertal participants (ages 11–14, premenarchal, or within 1 year of menarche) completed an assessment of stressful life events, and provided weekly salivary hormone collections [estrone, testosterone, dehydroepiandrosterone (DHEA)] and mood assessments for 8 weeks. Linear mixed models tested whether stressful life events provided a context in which within-person changes in hormones predicted weekly affective symptoms. Results indicated that exposure to stressful life events proximal to the pubertal transition influenced the directional effects of hormone change on affective symptoms. Specifically, greater affective symptoms were associated with increases in hormones in a high stress context and decreases in hormones in a low stress context. These findings provide support for stress-related hormone sensitivity as a diathesis for precipitating affective symptoms in the presence of pronounced peripubertal hormone flux.

Topiramate (TOP) is a psychotropic drug prescribed for the treatment of epilepsy in children older than 2 years of age and for migraine prophylaxis in adolescents. There is evidence that TOP promotes negative effects on the reproductive system of male rats. This study aimed to evaluate the immediate and late treatment effects of TOP during childhood and adolescence on the male rat reproductive system. Two experimental groups received 41 mg/kg of TOP daily, by gavage, from postnatal day (PND) 16 to 28 (TOPc group) or from PND 28 to 50 (TOPa group). Control groups (CTRc group or CTRa group) received water daily. Half of the anim–als were evaluated 24 h after the end of treatment (PND 29 and PND 51, respectively) and the remainder were evaluated in adulthood (PND120). The following parameters were determined: anogenital distance, sperm evaluation, testis’ histomorphometry and plasma testosterone concentration. At PND 120, the volume (CTRc:62.58 ± 2.13; TOPc: 54.54 ± 2.10*%, p = 0.018) and total length (CTRc: 25.48 ± 1.61; TOPc: 18.94 ± 2.41*, p = 0.035) of seminiferous tubules were decreased and the volume of interstitial tissue (CTRc:37.41 ± 2.13; TOPc: 45.45 ± 2.09*%, p = 0.018) and number of Leydig cells/testis (CTRc: 277.00 ± 36.70; TOPc: 400.20 ± 13.23*, p = 0.013) were increased in the TOPc group. The other parameters remained similar between the groups. Therefore, the present study contributes to our understanding that childhood treatment with TOP has an impact on the rat reproductive system in adulthood, suggesting that this period is more sensitive to TOP exposure than adolescence.

Childhood psychosocial stressors have been proposed to favour fast life history strategies promoting earlier puberty in females. However, studies demonstrating this association often do not elucidate causal mechanisms, nor account for greater childhood energetic availability – also known to promote rapid growth and earlier puberty. To assess the extent to which such confounding has been considered, we conducted a systematized review to identify studies examining measures of both prepubertal growth (e.g. weight, height) and psychosocial stressors (e.g. adversity, father absence) in relation to female pubertal timing. A total of 1069 non-duplicated studies were identified across five databases. Twenty studies met selection criteria for critical review following independent screening of titles, abstracts and manuscripts. Within these studies, measures indicative of rapid childhood growth were more consistently associated with earlier pubertal timing than were measures of psychosocial stress. We discuss future research directions to investigate the impact of psychosocial stress on pubertal timing more robustly, including methodological and mechanistic considerations, and contextualization of findings by socioecological environments.