BACKGROUND: Ambient air pollutants have been suggested to affect pubertal development. Nevertheless, current studies indicate inconsistent effects of these pollutants, causing precocious or delayed puberty onset. This study aimed to explore the associations between long-term exposure to particulate matter with aerodynamic diameters ≤ 2.5 μm (PM2.5) along with its components and menarche timing among Chinese girls.
METHODS: Self-reported age at menarche was collected among 855 girls from China Health and Nutrition Survey 2004 to 2015. The pre-menarche annual average concentrations of PM2.5 and its components were calculated on the basis of a long-term (2000-2014) high-resolution PM2.5 components dataset. Generalized linear models (GLM) and logistic regression models were used to analyze the associations of exposure to a single pollutant (PM2.5, sulfate, nitrate, ammonium, black carbon and organic matter) with age at menarche and early menarche (< 12 years), respectively. Weighted quantile sum methods were applied to examine the impacts of joint exposure on menarche timing.
RESULTS: In the adjusted GLM, per 1 µg/m3 increase of annual average concentrations of nitrate and ammonium decreased age at menarche by 0.098 years and 0.127 years, respectively (all P < 0.05). Every 1 µg/m3 increase of annual average concentrations of PM2.5 (OR: 1.04, 95% CI: 1.00-1.08), sulfate (OR: 1.23, 95% CI: 1.01-1.50), nitrate (OR: 1.23, 95% CI: 1.06-1.43) and ammonium (OR: 1.32, 95% CI: 1.06-1.66) were significantly positively associated with early menarche. Higher level of joint exposure to PM2.5 and its components was associated with 11% higher odds of early menarche (P = 0.04). Additionally, the estimated weight of sulfate was the largest among the mixed pollutants.
CONCLUSIONS: Long-term exposure to PM2.5 and its components could increase the risk of early menarche among Chinese girls. Moreover, sulfate might be the most critical components responsible for this relationship. Our study provides foundation for targeted prevention of PM2.5 components.

This study aimed to analyze the growth patterns of height and foot length (FL) among Chinese children aged 3-18 and examine their associations with puberty development.
A cross-sectional survey was conducted in September 2022 in Beijing. Data were collected through questionnaires and on-site physical examinations. The growth patterns and velocity of height and FL in different age groups were described, and their associations with puberty development were analyzed.
From an age perspective, the peak FL growth occurred between 9 and 11 years (boys were 11 years and girls were 9 years), while the peak height growth occurred at 11 ~ 13 years for boys and 9 ~ 11 years for girls. Additionally, boys and girls reached 99.0% of their final FL at the ages of 14 and 13, respectively, while they reached 99.0% of their final height at the ages of 16 and 15, respectively. From the perspective of Tanner stage, the age of peak FL growth in boys coincided with the age of the G2 stage, while in girls it occurred slightly earlier than the mean age of the B2 stage. The peak height growth for both boys and girls occurred between Tanner stages 2 and 3.
Boys and girls reach their peak FL growth at 11 and 9 years old, respectively, which were both 2 years earlier than their peak height growth. The peak FL growth occurred around the onset of puberty, while the peak height growth occurred between Tanner stages 2 and 3.

Pineal cysts have long been considered a benign intracranial variation. However, in our clinical practice, it has been observed that some children with central precocious puberty (CPP) who have pineal cysts experience rapid progression in adolescent development. In recent years, there has been a significant increase in the prevalence of CPP in girls, leading to more diagnoses of CPP among children with pineal cysts. Despite this, there is no consensus regarding whether pineal cysts contribute to CPP as one of its organic factors. This study aimed to analyze the clinical characteristics of pineal cysts in children with CPP and explore the potential effects of pineal cysts on puberty development.
This single-center study retrospectively analyzed clinical data from girls aged 3 to 10 years who underwent head/pituitary magnetic resonance imaging at the Children\'s Hospital Affiliated to Zhengzhou University between 2019 and 2022. The study categorized the detection rates of pineal cysts based on systematic disease classification and compared the rates of cyst detection between girls diagnosed with CPP and those without CPP. Subsequently, CPP-diagnosed girls with pineal cysts were examined. Among CPP-diagnosed girls meeting the study\'s criteria, those with pineal cysts formed the \'cyst group,\' while those without cysts were matched in a 1:1 ratio based on age and body mass index to form the \'non-cyst group.\' Comparative analyses were conducted to assess the clinical characteristics between these two groups. CPP-diagnosed girls with cysts were further subdivided into three groups according to cyst size (≤5 mm, 5.1-9.9 mm, and ≥10 mm) to investigate potential differences in clinical characteristics among these subgroups. The study involved an analysis of clinical data from girls diagnosed with CPP and included imaging follow-ups to explore the progression of pineal cysts over time.
Among the 23,245 girls who underwent head/pituitary magnetic resonance imaging scans, the detection rate of pineal cysts was 3.6% (837/23,245), with most cases being associated with endocrine diseases. The detection rate of pineal cysts in CPP patients was 6.4% (262/4099), which was significantly higher than the 3.0% (575/19,146) in patients without CPP. In comparison to the non-cyst group, the cyst group exhibited statistically significant increases in estradiol levels, peak luteinizing hormone (LH) levels, peak LH/follicle-stimulating hormone (FSH) ratios, uterine body length, and cervix length (P < 0.001). As cyst size increased, there were significant rises in LH peak, peak LH/FSH ratio, uterine body length, and cervical length (P < 0.01). Estradiol levels and left ovarian volume also showed an increasing trend (P < 0.05). Among girls who underwent follow-up imaging, 26.3% (5/19) exhibited an increase in cyst size.
Pineal cysts are relatively common in children with CPP. They may affect the pubertal development process, with larger cysts correlating to faster pubertal development. Therefore, the authors hypothesize that pineal cysts may trigger CPP in some cases, especially when the cysts are larger than 5 mm in size, as indicated by our data.

Pharmaceutical and personal care products (PPCPs) include a wide range of drugs, personal care products and household chemicals that are produced and used in significant quantities. The safety of PPCPs has become a growing concern in recent decades due to their ubiquitous presence in the environment and potential risks to human health. PPCPs have been detected in various human biological samples, including those from children and adolescents, at concentrations ranging from several ng/L to several thousand μg/L. Epidemiological studies have shown associations between exposure to PPCPs and changes in the timing of puberty in children and adolescents. Animal studies have shown that exposure to PPCPs results in advanced or delayed pubertal onset. Mechanisms by which PPCPs regulate pubertal development include alteration of the hypothalamic kisspeptin and GnRH networks, disruption of steroid hormones, and modulation of metabolic function and epigenetics. Gaps in knowledge and further research needs include the assessment of environmental exposure to pharmaceuticals in children and adolescents, low-dose and long-term effects of exposure to PPCPs, and the modes of action of PPCPs on pubertal development. In summary, this comprehensive review examines the potential effects of exposure to PPCPs on pubertal development based on evidence from human and animal studies.

BACKGROUND: Previous studies showed phthalates and UV filters are endocrine-disruptive and associated with puberty. However, few studies have examined effects of mixed exposure.
METHODS: Six 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.
RESULTS: Six 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)).
CONCLUSIONS: Our 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.

Animal studies suggest that exposure to certain neonicotinoids may interfere with the normal function of endocrine system in mammals. However, evidence from human studies is limited.
This study conducted a cross-sectional analysis to examine urinary neonicotinoids concentrations in Chinese adolescents and its association with pubertal development.
774 urine samples from 439 boys (median age: 13.7 years; 25th-75th percentile: 12.7-14.5 years) and 335 girls (median age: 13.7 years; 25th-75th percentile: 12.7-14.5 years) were collected for determination of ten neonicotinoids (imidacloprid, nitenpyram, acetamiprid, thiacloprid, imidaclothiz, thiamethoxam, clothianidin, dinotefuran, flonicamid, sulfoxaflor) and one metabolite (N-desmethyl-acetamiprid). Urinary creatinine was detected for concentration adjustment. Pubertal development including pubic hair, axillary hair, genitalia (boys), testicular volume (boys) and breast (girls) assessed by Tanner stages and others (spermarche, facial hair for boys and menarche for girls) were obtained by physical examination and questionnaire. Logistic and bayesian kernel machine regression were used to investigate the association between neonicotinoids concentrations and pubertal developments.
High detection rates ranged from 72.0% to 100.0% for all neonicotinoids. Boys and girls with thiacloprid concentration at the >75th percentile had lower stage of genitalia development (OR: 0.83, 95% CI: 0.33-0.93) and higher stage of axillary hair development (OR: 1.46, 95% CI: 1.12-3.41), respectively, compared with those at the <25th percentile. The estimate change in genitalia stage was significantly different at or above the 75th percentile concentration of neonicotinoids mixture compared to the 50th percentile concentration. No associations were found between other urinary neonicotinoids and other indicators of puberty.
Higher thiacloprid concentration was associated with delayed genitalia development in boys and early axillary hair development in girls. Neonicotinoids mixture was negatively associated with genitalia stage in the joint effect. Given the characteristic of the cross-sectional study, our results need further confirmation of the causal relationship.

Chlorocholine chloride (CCC) promote plant growth as a regulator. Emerging evidence by our group showed that CCC might restrain the puberty onset and impair the reproductive functions in male rats through HPT axis. In this study, we further investigated the effects of prenatal CCC exposure on pubertal development, reproduction of male offspring in rats and explored the underlying mechanisms. The results showed that CCC of 137.5 and 200 mg/kg bw/day delayed the age of preputial separation (PPS), decreased the sperm motility of male offspring. PP1γ2 which is an essential protein in spermatogenesis reduced in 137.5 and 200 mg/kg bw/day groups. Crucial hormones involved in hypothalamic-puititary-testicular (HPT) axis decreased at postnatal day (PND) 30. It was indicated that CCC exposure in pregnancy might disturb the pubertal development, reproductive functions of male offspring through HPT axis and disturb the sperm motility through PP1γ2.

Blood pressure (BP) increased with age and height development, but little was known about the effect of pubertal development on blood pressure in children. A cross-sectional study was performed among 4146 children aged 7-12 years old in China. Pubertal development was assessed based on breast stages and testicular volume. The associations of pubertal development with BP levels and the rate of elevated blood pressure (EBP) were quantified using multiple linear and logistic regressions. We found that pubertal developmental level was positively correlated with BP, and children who experienced puberty onset and early pubertal timing had higher BP levels and prevalence of EBP. After adjusting for covariates, children experienced puberty onset had 3.84 and 2.24 mmHg increase in systolic blood pressure and diastolic blood pressure, and 70%, 53%, and 62% increased odds of EBP, ESBP, and EDBP, respectively, compared with those without puberty onset. Similar results were observed for children who had early pubertal timing. The change of BP in puberty is greater and the association between pubertal development and BP is stronger in girls than boys. These findings suggested that pubertal development could be an important independent factor and one critical period for the EBP progress. Monitoring and management of pubertal development are necessary particularly among girls.

Perfluoroundecanoic acid (PFUnA) is one of long-chain perfluoroalkyl carboxylic acids. However, the effect of PFUnA on pubertal development of Leydig cells remains unclear. The goal of this study was to investigate the effect of PFUnA on Leydig cell development in pubertal male rats. We orally dosed male Sprague-Dawley rats (age 35 days) with PFUnA at doses of 0, 1, 5, and 10 mg/kg/day from postnatal day (PND) 35 to PND 56. Serum testosterone and luteinizing hormone levels were remarkably reduced by PFUnA at ≥1 mg/kg while serum follicle-stimulating hormone levels were lowered at 5 and 10 mg/kg. PFUnA down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Hsd11b1, Insl3, Nr5a1, Fshr, Dhh, Sod1, and Sod2 and their proteins in the testis and the expression of Lhb and Fshb in the pituitary. PFUnA reduced Leydig cell number at 5 and 10 mg/kg. PFUnA induced oxidative stress and increased autophagy. These may result from the inhibition of phosphorylation of mTOR, AKT1, AKT2, and ERK1/2 in the testis. In conclusion, PFUnA exhibits inhibitory effects on pubertal Leydig cell development possibly via inducing oxidative stress and increasing autophagy.

Congenital lipoid adrenal hyperplasia (LCAH), as the most severe form of congenital adrenal hyperplasia (CAH), is caused by mutations in the steroidogenic acute regulatory protein (STAR). Affected patients were typically characterized by adrenal insufficiency in the first year of life and present with female external genitalia regardless of karyotype. Non-classic LCAH patients usually present from 2 to 4 years old with glucocorticoid deficiency and mild mineralocorticoid deficiency, even develop naturally masculinized external genitalia at birth when they have 46,XY karyotype. We described thirty patients from unrelated Chinese families, including three non-classic LCAH ones. Four novel mutations were reported, including c.556A > G, c.179-15G > T, c.695delG and c.306 + 3_c.306 + 6delAAGT. The c.772C > T is the most common STAR mutation in Chinese population, suggesting a possibility of founder effect. Enzymatic activity assay combined with clinical characteristics showed a good genotype-phenotype correlation in this study. Residual STAR activity more than 20 % may be correlated with non-classic LCAH phenotype. We support the perspective that onset age may be affected by multiple factors and masculinization should be the main weighting factor for diagnosis of non-classic LCAH. Compared with 46,XX LCAH patients, less 46,XY ones were found in our report. A less comprehensive inspection and an easy diagnosis due to classical phenotype both would reduce the possibility of 46,XY LCAH patients to be referred to specialists or geneticists.