Early Puberty In Girls Research Articles

The Effects of Nutrition, Health, Psychological and Socio-Economic Factors on Precocious Puberty in Girls

Early puberty or precocious puberty in girls, characterized by the beginning of puberty before turning 8, is a growing concern worldwide. This research paper explores the multifactorial influences of nutrition, health, psychological stressors, and socio-economic factors on the incidence of early puberty in girls. By examining existing literature, the paper highlights the complex interactions among these elements and provides insights into potential interventions. An understanding of these factors is crucial for developing effective preventive and therapeutic strategies. Recommendations are made to promote balanced diets, improve healthcare access, provide psychological support, and address socio-economic disparities to mitigate the risk of precocious puberty and its associated health consequences.

The Effects of Nutrition, Health, Psychological and Socio Economic Factors on Precocious Puberty in Girls

Early puberty or precocious puberty in girls, characterized by the beginning of puberty before turning 8, is a growing concern worldwide. This research paper explores the multifactorial influences of nutrition, health, psychological stressors, and socio-economic factors on the incidence of early puberty in girls. By examining existing literature, the paper highlights the complex interactions among these elements and provides insights into potential interventions. An understanding of these factors is crucial for developing effective preventive and therapeutic strategies. Recommendations are made to promote balanced diets, improve healthcare access, provide psychological support, and address socio-economic disparities to mitigate the risk of precocious puberty and its associated health consequences.

Identification of Environmental Compounds That May Trigger Early Female Puberty by Activating Human GnRHR and KISS1R.

There has been an alarming trend toward earlier puberty in girls, suggesting the influence of an environmental factor(s). As the reactivation of the reproductive axis during puberty is thought to be mediated by the hypothalamic neuropeptides kisspeptin and gonadotropin-releasing hormone (GnRH), we asked whether an environmental compound might activate the kisspeptin (KISS1R) or GnRH receptor (GnRHR). We used GnRHR or KISS1R-expressing HEK293 cells to screen the Tox21 10K compound library, a compendium of pharmaceuticals and environmental compounds, for GnRHR and KISS1R activation. Agonists were identified using Ca2+ flux and phosphorylated extracellularly regulated kinase (p-ERK) detection assays. Follow-up studies included measurement of genes known to be upregulated upon receptor activation using relevant murine or human cell lines and molecular docking simulation. Musk ambrette was identified as a KISS1R agonist, and treatment with musk ambrette led to increased expression of Gnrh1 in murine and human hypothalamic cells and expansion of GnRH neuronal area in developing zebrafish larvae. Molecular docking demonstrated that musk ambrette interacts with the His309, Gln122, and Gln123 residues of the KISS1R. A group of cholinergic agonists with structures similar to methacholine was identified as GnRHR agonists. When applied to murine gonadotrope cells, these agonists upregulated Fos, Jun, and/or Egr1. Molecular docking revealed a potential interaction between GnRHR and 5 agonists, with Asn305 constituting the most conservative GnRHR binding site. In summary, using a Tox21 10K compound library screen combined with cellular, molecular, and structural biology techniques, we have identified novel environmental agents that may activate the human KISS1R or GnRHR.

Inter-arm bone mass and size asymmetries in children tennis players are maturity status specific: a 9-month study on the effects of training time across pubertal change and somatic growth

PurposeBone growth with exercise is best assessed by tennis-induced inter-arm asymmetries. Yet, the effects of training and maturation across puberty were unclear. This study explored arm bone growth across 9 months of training in 46 tennis players 7–14 years (25 boys, 21 girls).MethodsBone mineral content (BMC) and bone area (BA) were measured from DXA scans. Pubertal status was assessed by Tanner stage (TS) and somatic growth by maturity offset (MO). Children were grouped as pre- (TS I–I), early (TS I–II), and mid/late pubertal (TS II–III).ResultsTraining time (TT) change in the three groups was 160–170, 190–230, and 200–220 h, respectively. Bone asymmetries were large in all groups (d > 0.8, P < 0.001): 5–18 g (9–21%) and 9–17 g (17–23%) in girls and boys, respectively, for BMC, and 5–15 cm2 (6–13%) and 9–15 cm2 (12–15%) in girls and boys (10–13%), respectively, for BA. BMC and BA change asymmetry peaked at pre-puberty in girls (56%, 46%) and at early puberty in boys (57%, 43%). Asymmetry gains varied with baseline asymmetry (41%) and change in TT (38%) and TS (17%) in BMC, and with baseline asymmetry (58%) and change in MO (17%) and TS (12%) in BA.ConclusionAll bone asymmetries were substantial. Tennis-induced bone gains were higher at pre- to early puberty in girls and at early to mid/late puberty in boys. Training enhanced mostly bone mass and maturity status enhanced mostly bone size; sex was not bone-change modeling impactful. Implications are discussed considering certain limitations.

THU204 Serum Vascular Endothelial Growth Factor-A Levels According To Pubertal State And Body Weight In Children

Abstract Disclosure: H. Nam: Grant Recipient; Self; Supported by a Korea University Grant. E. Kang: None. Y. Rhie: None. K. Lee: None. Objectives: Childhood obesity may lead to early puberty in girls, however, it remains unclear whether early thelarche in overweight girls is related to central activation of the gonadotropin releasing hormone-gonadotropin axis. Vascular endothelial growth factor-A (VEGF-A) is essential for governing angiogenesis in adipose tissue. We assessed serum VEGF-A level according to pubertal state and weight in girls. Patients and Methods: Total 165 girls were classified as prepuberty (n=40), puberty with peak LH &amp;lt;5.0 IU/L (n=60), and puberty with peak LH ≥5.0 IU/L (n=65). Serum VEGF-A, sex hormone, gonadotropin level and bone age were analyzed according to pubertal state and overweight including obesity. We measured serum level of VEGF-A using ELISA kit. Results: Their chronological age were similar (7.8±1.2, 7.9±0.8, and 8.0±0.9 years, p=0.410 in prepuberty, puberty with peak LH &amp;lt;5.0 IU/L, puberty with peak LH ≥5.0 IU/L, respectively). The mean VEGF-A level was higher in puberty girls (399.3±206.2, 633.5±473.0, 605.7±392.4 pg/mL, P=0.009) and was significantly correlated with Tanner stage (r=0.224, p=0.004), BMI SDS (r=0.191, p=0.014), and weight SDS (r=0.202, p=0.009). When sub-analysis with the degree of obesity, VEGF-A level (802.2±556.0 pg/mL) was highest in overweight puberty girls with peak LH &amp;lt;5 IU/L and was significantly correlated with peak LH (r=0.397, p=0.044) and peak LH/FSH (r=0.409, p=0.038). Conclusions: Our study showed higher VEGF-A levels in overweight puberty girls. Obesity-associated VEGF-A rise may involve in the progression of precocious puberty. Further studies related to pathophysiological mechanism are needed. Presentation: Thursday, June 15, 2023

Identification of urine biomarkers associated with early puberty in children: An untargeted metabolomics analysis

A trend toward earlier pubertal maturation in both sexes has been shown in many countries. Early puberty affects an increasing proportion of children for reasons that remain obscure. Novel candidate biomarkers are strongly needed. We sought to apply untargeted metabolomic profiling to identify triggering mechanisms and candidate biomarkers in children with early puberty. Participants aged 7 – 12 years old were recruited directly from two elementary schools of Bengbu, Anhui Province, China, from Feb 2021 to May 2021. Early puberty was determined by breast and testicular development at baseline (May 2021) and 6-month later. Ultra-high-performance liquid chromatography-based untargeted metabolomic profiling was performed on urine samples of children with early puberty and control subjects. Metabolomic profiling for early puberty in a sex dependent manner. For boys, we identified several perturbed pathways, including histidine metabolism, glycine, serine and threonine metabolism, and selenoamino acid metabolism, associated with early puberty. In contrast, there were differences in pyruvate metabolism, one carbon pool by folate, and D-glutamine and D-glutamate metabolism pathways in girls with early puberty compared with controls. In addition, 4-hydroxyhippuric acid and 5-methoxytryptophol were shown as potential independent diagnostic biomarker for early puberty in boys, 3-hydroxybenzoic acid and glutaminylproline were shown as early biomarker for early puberty in girls, achieving area under the ROC curve of 0.71 and 0.72 in discriminating early puberty boys, and 0.70 and 0.74 in discriminating early puberty girls from controls. Through metabolomic analysis, we have identified metabolic perturbations and potential biomarkers of early puberty.

Mixed exposure to phthalates and organic UV filters affects Children's pubertal development in a gender-specific manner

BackgroundPrevious studies showed phthalates and UV filters are endocrine-disruptive and associated with puberty. However, few studies have examined effects of mixed exposure. MethodsSix phthalate metabolites and 12 organic UV filters were detected among 223 school-age children. Puberty development was evaluated at baseline and after 18 months of follow-up. Ordered logistic regression models, least absolute shrinkage and selection operator (LASSO) regression and quantile-based g-computation (qgcomp) were used to evaluate relationships between phthalate metabolites or UV filters exposure and pubertal development. ResultsSix phthalate metabolites and 5 UV filters were detectable in urine samples. In boys, BP-3 and 4′-MAP were negatively associated with genital (ORBP-3 = 0.52, (0.27, 0.93), OR4′-MAP = 0.45, (0.25, 0.74)) and pubic hair development (ORBP-3:0.24, (0.05, 0.76), OR4′-MAP:0.24, (0.05, 0.77)). In girls, MEP levels were associated with advanced breast development (OR: 1.29, (1.04, 1.64)). LASSO regression identified BP-3, 4′-MAP, and OD-PABA for inverse associations with pubertal development in boys. MEP was related to an increase in girls' breast development (OR: 1.64, (1.08, 2.63)). Overall mixture was related to a 70% reduction in boys' genital development stage, with a larger effect size than a single chemical in qgcomp. Mixed exposure was associated with girls' earlier puberty onset (OR: 2.61, (1.06, 6.42)). ConclusionsOur results suggested higher levels of phthalate metabolites and UV filters were associated with delayed pubertal development in boys but with earlier puberty in girls. Higher effect size of joint exposure than single chemicals suggested phthalates and UV filters might have synergistic effects on puberty and distort adolescent endocrine function together.

Influence of Health Education with Audio Visual Media on Anxiety Facing Menarche with Students Elementary Schools 006 Long Iram

Introduction: Early puberty in girls is one of the best examples of adolescent mental health problems including anxiety. The results of Riskesdas show that based on reports of respondents who have experienced menstruation, the average age of menarche is 13 years (20%) with an earlier occurrence at the age of less than 9 years and some delaying up to 20 years. Objective: To determine the effect of health education with audiovisual media on anxiety facing menarche in students of Elementary Schools 006 Long Iram. Methods: Experimental research design with pre-experimental design one group pretest posttest. Results and Discussion: It was found that before the intervention providing education with audiovisual media, most of them experienced moderate anxiety as many as 21 people (61.8%), after the intervention most of the anxiety became a mild category as many as 21 people (61.8%). A total of 18 people had anxiety after the health education intervention with audio-visual media about menarche decreased compared to before the intervention. Conclusion: There are differences in student anxiety before and after being given health education with audio-visual media about menarche at Sekolah Dasar 006 Long Iram students

Association of the consumption of common drinks with early puberty in both sexes.

We examined the effect of sugar-sweetened beverages (SSB) and common drink intake on pubertal development in both sexes. Data were retrieved from Taiwan Children Health Study, which involved detailed pubertal stage assessments of 2,819 schoolchildren aged 11 years in 2011-2012. Drawings of secondary sexual characteristics and self-reported age at menarche or voice breaking were used to assess pubertal stages. Dietary intake was assessed using a detailed semi-quantitative food frequency questionnaire. Generalized estimating equation modeling was applied to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to represent the effects of each drink on early pubertal development outcomes. In boys, an one cup/day increment of a SSB was associated with earlier voice breaking (β = -0.12; 95% CI = -0.20, -0.04), whereas consuming yogurt (≥2 cups/day) was a protective factor against early puberty (OR = 0.78; 95% CI = 0.73, 0.83). In girls, SSB consumption was associated with increased risk of early puberty in a dose-response manner, and a similar protective effect of yogurt consumption and fermented probiotic drink (≥2 cups/day) against early puberty was observed (OR = 0.96; 95% CI = 0.94, 0.99). Furthermore, the intake of both total sugar and added sugar within SSBs increased risk of early puberty in girls but not in boys. Sugar-sweetened beverages were associated with early puberty, and probiotic drinks appeared to mitigate this link. These findings indicate that the gut-brain axis could play a crucial role in sexual maturation.

Childhood exposure to non-persistent pesticides and pubertal development in Spanish girls and boys: Evidence from the INMA (Environment and Childhood) cohort

This study assessed cross-sectional associations between urinary metabolites of non-persistent pesticides and pubertal development in boys and girls from urban and rural areas in Spain and examined effect modification by body mass index (BMI). Four metabolites of insecticides (TCPy, metabolite of chlorpyrifos; IMPy, metabolite of diazinon; DETP, non-specific metabolite of organophosphates; 3-PBA, metabolite of pyrethroids) and the metabolite of ethylene-bis-dithiocarbamate fungicides (ETU) were quantified in urine collected in 2010–2016 from 7 to 11-year-old children (606 girls, 933 boys) participating in the INMA Project. Pubertal development was ascertained by Tanner stages and/or parent-reported Pubertal Development Scale (PDS). Associations between pesticide metabolites and odds of being in stage 2+ for breast development (girls), genital development (boys), pubic hair growth (girls and boys), and/or overall puberty onset, gonadarche, and adrenarche (PDS for girls and boys) were examined by mixed-effect logistic regression. Effect modification by BMI was explored by interaction terms and stratified analysis. In girls, DETP and ETU concentrations>75th percentile (P75) were associated with higher odds of overall puberty development (OR [95%CI] = 1.86 [1.07–3.24] and 1.71 [1.03–2.83], respectively, for > P75 vs. undetected concentrations), while ETU > P75 was also associated with higher odds of breast development (OR [95%CI] = 5.55 [2.83–12.91]), particularly in girls with underweight/normal weight (OR [95%CI] = 10.08 [2.62–38.76]). In boys, detection of TCPy (40%) and 3-PBA (34%) was associated with higher odds of genital development (OR [95%CI] = 1.97 [1.08–3.57] and 2.08 [1.15–3.81], respectively), and the association with 3-PBA was observed in boys with overweight/obesity alone. In addition, ETU > P75 was associated with higher odds of genital development in boys with underweight/normal weight (OR [95%CI] = 2.89 [1.08–7.74]) but higher DETP with lower odds of puberty in boys with overweight/obesity (OR [95%CI] = 0.94 [0.89–0.99] per log-unit increase in concentration). Results suggest an association of childhood exposure to ETU and certain insecticides with earlier puberty in girls and boys that may be modified by child BMI.

Associations Between Childhood Obesity and Pubertal Timing Stratified by Sex and Race/Ethnicity.

Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio= 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio= 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.

Are Black Girls Exhibiting Puberty Earlier? Examining Implications of Race-Based Guidelines.

Are Black Girls Exhibiting Puberty Earlier? Examining Implications of Race-Based Guidelines.

Early and delayed puberty among Iranian children with obesity.

It has been hypothesized that puberty onset is disturbed as the children gain more weight. This study aimed to investigate the prevalence and risk factors of the puberty disturbances among children with obesity in Tehran, Iran. This study was performed as a cross-sectional study, investigating 168 children with obesity from Tehran, Iran, from March 2018 to February 2019. BMI percentile more than 95% was considered as the inclusion criteria. Seventy-eight (46.4%) of the assessed children were females. The mean weight, height, BMI were 89.65 (±11.01) kg, 169.88 (±8.32) centimeters and 31.13(±3.8) kg/m2, respectively. There was no difference between males and females regarding the early puberty (P=0.098), but delayed puberty was significantly higher among males (P=0.029). Our results indicated higher birth weight is associated with earlier onset of obesity in children (P=0.044). Our study demonstrated no association between obesity and early puberty in girls; however, boys with obesity had delayed puberty. We also found higher birth weight is associated with earlier onset of obesity, putting light on the importance of preventive interventions.

Body composition in sexual precocity.

In this review, we have summarized the current data on the effect of sexual precocity and treatment with gonadotropin-releasing hormone analogues (GnRHa) on body composition. Higher body weight and weight gain in infancy and childhood may increase the risk of early puberty in girls. The relation between BMI and pubertal onset in boys is controversial. Current studies draw attention to the fact that a similar relationship may exist in boys too. Obesity prevalence is high among girls with central precocious puberty (CPP) and treatment with GnRHa has a different effect on BMI according to baseline body composition. Although BMI values of normal weight girls tend to increase under treatment, they return to normal following treatment. The few studies that have followed up body composition longitudinally in girls show a gradual increase in adiposity, decrease in muscle mass and bone mineral density during GnRHa treatment, whereas bone mass was preserved after treatment. Adequate data are not available in boys to determine the effect of GnRHa therapy on body composition. Body composition and fat distribution should be monitored longitudinally in patients with CPP treated with GnRHa to ascertain the long-term effects of therapy.

Obesity-related genetic polymorphisms are associated with the risk of early puberty in Han Chinese girls.

To explore the association between obesity and precocious puberty from the perspective of genetic polymorphism. Two hundred and ninety-eight pairs of girls in early puberty and age-matched controls (±3 months) were recruited. The genotypes of four obesity-related single-nucleotide polymorphism (SNP) loci (rs10968576, rs12935153, rs4674340 and rs7635103) were determined and the effect of variation on early puberty in Chinese Han girls was evaluated. The unstimulated luteinizing hormone (LH), follicle-stimulating hormone and estradiol levels were also measured to determine the relationship with SNP polymorphisms. The effect allele A of rs12935153 was associated with early puberty (odds ratio [OR] = 1.256, 95% confidence interval [CI]: 1.010-1.585), but the significance disappeared after multiple comparisons. After adjusting for body mass index, rs12935153 variation increased the risk of early puberty in additive (OR = 1.589, 95% CI: 1.222-2.066), dominant (OR = 1.788, 95% CI: 1.210-2.642) and recessive (OR = 1.915, 95% CI: 1.207-3.038) models of inheritance. Individuals harbouring AA genotype in rs12935153 had a risk of higher LH levels than that of wild type (OR = 1.668, 95% CI: 1.093-2.546). The association between obesity and precocity can be explained from a genetic perspective. Our study suggests that variations in rs12935153 increase the risk of early puberty in Chinese girls. Further studies are needed to verify our findings.

Positive effect of combined exercise on adipokines levels and pubertal signs in overweight and obese girls with central precocious puberty

BackgroundThe prevalence of precocious puberty is increasing. Obesity has been demonstrated to be associated with changes in the adipokine profile and incidence of early puberty in girls. This study assessed the pubertal signs, the levels of adiponectin, resistin, and tumor necrosis factor-alpha (TNF-α) after 12 weeks of combined exercise and 4 weeks of detraining in overweight and obese girls with precocious puberty.MethodsThirty overweight and obese girls (aged 7–9) with precocious puberty, who had received Triptorelin, were randomly divided into two groups (15 exercise and 15 control). Initially, serum levels of adiponectin, resistin, TNF-α, luteinising hormone (LH), and follicle-stimulating hormone (FSH) and the signs of puberty progression (bone age, uterine length, and ovarian volume) were measured. The exercise group performed 60 min of combined (aerobic and resistance) exercise three times/week for 12 weeks. The control group did not receive any exercise. 48 h after the last training session and after 4 weeks of detraining, all research variables were measured (also in the control group). The statistical method used for data analysis was repeated measures ANOVA.ResultsIn the exercise group, adiponectin significantly increased and resistin significantly decreased after 12 weeks. After 4 weeks of detraining, adiponectin significantly decreased, but resistin significantly increased. TNF-α levels did not change significantly during the study. There was no significant difference in all of the factors in the control group. Throughout the 16-week study period, the rate of puberty and LH significantly decreased in both exercise and control groups, but FSH, LH/FSH and ovarian volume significantly decreased in the exercise group alone (P<0.05).ConclusionsCombined exercise increased adiponectin and decreased resistin and the rate of puberty. However, after 4 weeks of detraining, these effects diminished but did not disappear.Trial registrationIRCT, IRCT56471. Registered 25 may 2021 - Retrospectively registered, https://fa.irct.ir/user/profile

Investigation of early puberty prevalence and time of addition thelarche to pubarche in girls with premature pubarche: two-year follow-up results.

.We aimed to determine the prevalence of early puberty in girls with premature pubarche and analyze the time interval between their pubarche and succeeding thelarche. This study included 60 female children with premature pubarche. We retrospectively collected clinical, laboratory, and radiological findings from all participants. We investigated the time interval between pubarche and thelarche in cases wherein premature pubarche was followed by thelarche. The mean age at onset of pubarche was 6.93 ± 0.79 yr old. Among the participants, 16.7% were preterm, 20% were small for gestational age (SGA), and 55% were overweight or obese. The mean time interval between pubarche and thelarche was 11.20 ± 7.41 mo. The mean serum DHEA-S level was higher in the preterm group (p = 0.016), and DHEA-S levels were generally higher in the SGA group (p = 0.004). This study documented the presence of being overweight or obese and having more advanced growth than their genetic potential in half of the patients who had premature pubarche. In addition to these identified risk factors, obesity-independent DHEA-S levels were observed to be higher in patients who had early puberty with the first six months of their follow-up considered to be the most critical time in predicting early puberty.

Endocrine-Disrupting Chemicals and Early Puberty in Girls.

In recent decades, pubertal onset in girls has been considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, with several reports suggesting that EDCs may have a role in the secular trend in pubertal maturation, at least in girls. However, relevant studies give inconsistent results. On the other hand, the majority of girls with idiopathic precocious or early puberty present the growth pattern of constitutional advancement of growth (CAG), i.e., growth acceleration soon after birth. Herein, we show that the growth pattern of CAG is unrelated to exposure to endocrine-disrupting chemicals and is the major determinant of precocious or early puberty. Presented data suggest that EDCs, at most, have a minor effect on the timing of pubertal onset in girls.

Pubertal Onset Occurs in Female Mice Lacking Paternally Expressed Dlk1 Despite Lower Leptin and Kisspeptin Levels

Abstract The timing of puberty in females is highly sensitive to metabolic cues and energy reserves. Epidemiologic studies indicate a relationship between increased body mass index and earlier puberty in girls. In contrast, a significant delay in puberty and menarche is seen in girls who have diminished body fat. Multiple peripheral hormones are responsible for transmitting metabolic information to hypothalamic kisspeptin and GnRH neurons. Sufficient levels of leptin, an adipose tissue hormone with a permissive/stimulatory effect on the metabolic control of reproduction, are required for puberty onset, reproductive function and fertility. Loss-of-function mutations in the Delta-like homolog 1 (DLK1) gene have been described in girls with central precocious puberty (CPP) and increased body fat, suggesting a link between metabolism and reproduction. DLK1 is a paternally expressed gene located on human chromosome 14q32.2 in a locus associated with Temple syndrome (TS). Dlk1 knockout mice display pre- and postnatal growth retardation, a phenotype that overlaps with TS. We have shown that Dlk1 deficient female mice achieved puberty at the same age as wild type mice, despite a considerably lower body weight (BW) (“relative precocious puberty”). To date, the mechanisms of action of Dlk1 in determining pubertal onset remain unknown. In this study, we used a Dlk1 deficient mouse model to explore the influence of Dlk1 in the regulation of reproductive axis, particularly its effects on leptin and/or kisspeptin, a major excitatory factor of the reproductive axis. By RT-qPCR and Western blot, we confirmed that both Dlk1 mRNA and protein were undetectable in the mediobasal hypothalamus (MBH) of Dlk+/p- (which inherited the mutant allele from their father), but it was present in Dlk+/+ mice. White adipose tissue (WAT) and blood were collected from Dlk+/p- and Dlk+/+ female mice at postnatal day (PND) 26, and MBH tissue was obtained from both groups at PND 15, 26 and 60. Quantification of total WAT showed no significant difference between Dlk1+/p-and Dlk1+/+ mice (p=0.8) at PND26, even after correction for total BW (p=0.29). Hypothalamic mRNA levels of Kiss1 and Socs3, a downstream mediator of leptin signaling, were measured by RT-qPCR. Kiss1 mRNA levels were significantly reduced in the MBH of Dlk1+/p- mice at PND15 and PND60, but no significant difference was found at PND 26. Socs3 expression was significantly lower in Dlk1+/p- mice (p=0.04) as a result of the reduced circulating levels of leptin (ELISA) observed in these mice at PDN26 (p=0.01). Our findings suggest that the absence of Dlk1 may attenuate the metabolic effects of low body weight and low leptin levels on puberty onset and that, as seen in humans, DLK1 is an important link between body weight and pubertal development. Finally, Dlk1 deficiency leads to activation of the reproductive axis despite lower levels of kisspeptin.

Hypothalamic Ceramides and the Ovarian Sympathetic System: At the Crossroads of Obesity and Puberty

Childhood obesity has been linked to early puberty in girls but the mechanism(s) by which overnutrition triggers pubertal onset remain unclear. In a recent issue of Cell Metabolism, Heras et al., 2020 implicate a non-canonical central ceramide to ovarian sympathetic innervation pathway as a novel mediator of obesity-induced pubertal acceleration in female rats.