-
Human Reproduction (Oxford, England) Feb 2021Is in utero exposure to mercury associated with the risk of precocious puberty?
STUDY QUESTION
Is in utero exposure to mercury associated with the risk of precocious puberty?
SUMMARY ANSWER
Prenatal exposure to high levels of mercury was associated with increased risk of precocious puberty, which was strengthened by concomitant maternal cardiometabolic conditions and adverse birth outcomes.
WHAT IS KNOWN ALREADY
The developing fetus is sensitive to mercury, a well-known endocrine disruptor which impacts the endocrine and reproductive system.
STUDY DESIGN, SIZE, DURATION
This study included 1512 mother-child pairs from the Boston Birth Cohort, a longitudinal cohort which recruited at birth and followed prospectively up to 21 years of age.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Mother-child pairs, from a predominantly urban minority population, were enrolled from 2002 to 2013. Prenatal exposure was assessed by maternal mercury concentration in red blood cells (RBCs) collected at 1-3 days after delivery. Precocious puberty was defined based on International Classification of Disease codes. Cox proportional hazards models were applied to the association between maternal mercury concentrations and the risk of precocious puberty.
MAIN RESULTS AND THE ROLE OF CHANCE
The median (interquartile range) of maternal mercury concentrations among children with and without precocious puberty were 3.4 (1.9-4.6) µg/l and 2.0 (1.0-3.7) µg/l, respectively. Compared to those in the lowest tertile for mercury, the highest tertile was associated with increased risk of precocious puberty, with an adjusted hazard ratio (HR) of 2.41, 95% CI: 1.16-5.03. In addition, concomitant maternal cardiometabolic conditions and adverse birth outcomes strengthened the effects of mercury on the risk of precocious puberty. The highest risk of precocious puberty was observed among children who had adverse birth outcomes and whose mothers had high RBC-mercury concentrations along with cardiometabolic conditions, with an HR of 4.76 (95% CI: 1.66-13.60) compared to children with favorable profiles of all three risk factors.
LIMITATIONS, REASONS FOR CAUTION
Precocious puberty was defined based on medical records, not on a direct assessment, which may have led to underdiagnosis and the inability to make a subclassification. The study included a predominately urban, low-income, minority population and as such our findings may not be widely generalizable.
WIDER IMPLICATIONS OF THE FINDINGS
Prenatal Hg exposure was associated with an increased risk of precocious puberty. This risk was strengthened by concomitant maternal cardiometabolic conditions during pregnancy and adverse birth outcomes.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the NIH/National Institute of Environmental Health Sciences, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Boston; Child; Cohort Studies; Female; Humans; Infant, Newborn; Mercury; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Puberty, Precocious
PubMed: 33367618
DOI: 10.1093/humrep/deaa315 -
International Journal of Public Health 2023To investigate the associations of obesity with growth and puberty in children. From November 2017 to December 2019, height, weight, and Tanner stages of 26,879...
To investigate the associations of obesity with growth and puberty in children. From November 2017 to December 2019, height, weight, and Tanner stages of 26,879 children aged 3-18 years in Fuzhou, China were assessed. The obese group was significantly taller than the non-obese group after age 4 years for both genders, yet there was no significant difference in height between obese and non-obese group after 15.5 years old for boys and 12.5 years old for girls. The inflection points of significant growth deceleration in obese and non-obese groups were 14.4 and 14.6 years old for boys, and 11.8 and 12.8 years old for girls, respectively. The proportions of testicular development in boys with obesity and non-obesity were 7.96% and 5.08% at 8.5-8.9 years old, respectively, while the proportions of breast development in girls were 17.19% and 3.22% at age 7.5-7.9 years old, respectively. Children with obesity were taller in early childhood, earlier onset of puberty and earlier cessation of growth than children with non-obesity of the same age. However, there was sex dimorphism on the effect of obesity on the incidence of precocious puberty.
Topics: Humans; Child; Child, Preschool; Female; Male; Adolescent; Cross-Sectional Studies; Obesity; Puberty; Puberty, Precocious; China
PubMed: 37255545
DOI: 10.3389/ijph.2023.1605433 -
Sleep Medicine Reviews Oct 2022Narcolepsy type 1 (NT1) is a rare neurological sleep disorder triggered by postnatal loss of the orexin/hypocretin neuropeptides. Overweight/obesity and precocious... (Review)
Review
Narcolepsy type 1 (NT1) is a rare neurological sleep disorder triggered by postnatal loss of the orexin/hypocretin neuropeptides. Overweight/obesity and precocious puberty are highly prevalent comorbidities of NT1, with a close temporal correlation with disease onset, suggesting a common origin. However, the underlying mechanisms remain unknown and merit further investigation. The main question we address in this review is whether the occurrence of precocious puberty in NT1 is due to the lack of orexin/hypocretin or rather to a wider hypothalamic dysfunction in the context of neuroinflammation, which is likely to accompany the disease given its autoimmune origins. Our analysis suggests that the suspected generalized neuroinflammation of the hypothalamus in NT1 would tend to delay puberty rather than hastening it. In contrast, that the brutal loss of orexin/hypocretin would favor an early reactivation of gonadotropin-releasing hormone (GnRH) secretion during the prepubertal period in vulnerable children, leading to early puberty onset. Orexin/hypocretin replacement could thus be envisaged as a potential treatment for precocious puberty in NT1. Additionally, we put forward an alternative hypothesis regarding the concomitant occurrence of sleepiness, weight gain and early puberty in NT1.
Topics: Child; Gonadotropin-Releasing Hormone; Humans; Narcolepsy; Neuroinflammatory Diseases; Neuropeptides; Orexins; Puberty, Precocious
PubMed: 36096986
DOI: 10.1016/j.smrv.2022.101683 -
The Journal of Clinical Endocrinology... Sep 2022The etiology of central precocious puberty (CPP) includes a spectrum of conditions. Girls younger than age 6 years with CPP should undergo cranial magnetic resonance...
CONTEXT
The etiology of central precocious puberty (CPP) includes a spectrum of conditions. Girls younger than age 6 years with CPP should undergo cranial magnetic resonance imaging (MRI), but it remains controversial whether all girls who develop CPP between the ages of 6 and 8 years require neuroimaging examination.
OBJECTIVE
To investigate the frequency of brain MRI abnormalities in girls diagnosed with CPP and the relationship between maternal factors, their age at presentation, clinical signs and symptoms, hormonal profiles, and neuroimaging findings.
METHODS
Data were collected between January 2005 and September 2019 from 112 girls who showed clinical pubertal progression before 8 years of age who underwent brain MRI.
RESULTS
MRI was normal in 47 (42%) idiopathic (I) scans, 54 (48%) patients had hypothalamic-pituitary anomalies (HPA) and/or extra-HP anomalies (EHPA), and 11 (10%) had brain tumors or tumor-like conditions (BT/TL), including 3 with neurological signs. Associated preexisting disorders were documented in 16. Girls with BT/TL had a higher LH peak after GnRH test (P = 0.01) than I, and those older than age 6 years had a higher craniocaudal diameter of the pituitary gland (P = 0.01); their baseline FSH and LH (P = 0.004) and peak FSH (P = 0.01) and LH (P = 0.05) values were higher than I. Logistic regression showed maternal age at menarche (P = 0.02) and peak FSH (P = 0.02) as BT/TL risk factors.
CONCLUSIONS
MRI provides valuable information in girls with CPP by demonstrating that fewer than half have a normal brain MRI and that few can have significant intracranial lesions after the age of 6, despite the absence of suggestive neurological signs.
Topics: Brain Neoplasms; Child; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Neuroimaging; Puberty, Precocious
PubMed: 35881919
DOI: 10.1210/clinem/dgac422 -
Journal of Pediatric and Adolescent... Oct 2022This is the first of two installments examining early puberty in girls. The first paper will discuss secular trends in onset of puberty and the possible mechanisms to... (Review)
Review
This is the first of two installments examining early puberty in girls. The first paper will discuss secular trends in onset of puberty and the possible mechanisms to explain these developments. The potential etiologies examined will include the role of endocrine-disrupting chemicals and obesogens, the impact of body mass index and obesity, genetic and biologic pathways, and the influence of lifestyle behaviors. The second paper of the two-part series will examine the potential health impacts of early puberty on young and adult women and offer suggestions for clinical management and public health prevention.
Topics: Adult; Biological Products; Body Mass Index; Female; Humans; Obesity; Puberty; Puberty, Precocious
PubMed: 35537618
DOI: 10.1016/j.jpag.2022.04.009 -
Frontiers in Endocrinology 2022In the last decade, deep learning methods have garnered a great deal of attention in endocrinology research. In this article, we provide a summary of current deep... (Review)
Review
In the last decade, deep learning methods have garnered a great deal of attention in endocrinology research. In this article, we provide a summary of current deep learning applications in endocrine disorders caused by either precocious onset of adult hormone or abnormal amount of hormone production. To give access to the broader audience, we start with a gentle introduction to deep learning and its most commonly used architectures, and then we focus on the research trends of deep learning applications in thyroid dysfunction classification and precocious puberty diagnosis. We highlight the strengths and weaknesses of various approaches and discuss potential solutions to different challenges. We also go through the practical considerations useful for choosing (and building) the deep learning model, as well as for understanding the thought process behind different decisions made by these models. Finally, we give concluding remarks and future directions.
Topics: Humans; Puberty, Precocious; Deep Learning; Thyroid Gland; Hormones
PubMed: 36339395
DOI: 10.3389/fendo.2022.959546 -
Advances in Pediatrics Aug 2020
Review
Topics: Body Height; Child; Disease Management; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious
PubMed: 32591066
DOI: 10.1016/j.yapd.2020.04.003 -
Pediatric Annals Jan 2023
Topics: Rats; Humans; Animals; Puberty, Precocious; Endocrinologists; Screen Time; Gonadotropin-Releasing Hormone
PubMed: 36625799
DOI: 10.3928/19382359-20221206-01 -
Journal of Neuroendocrinology Feb 2022Puberty is a crucial biological process normally occurring at a specific time during the lifespan, during which sexual and somatic maturation are completed, and... (Review)
Review
Puberty is a crucial biological process normally occurring at a specific time during the lifespan, during which sexual and somatic maturation are completed, and reproductive capacity is reached. Pubertal timing is not only determined by genetics, but also by endogenous and environmental cues, including nutritional and metabolic signals. During the last decade, we have learned much regarding the essential roles of kisspeptins and the neuropeptide pathways that converge on these neurones to modulate kisspeptin signalling, as well as neurokinin B and dynorphin, the co-transmitters of Kiss1 neurones in the arcuate nucleus, and the effects of melanocortins on puberty. Indeed, melanocortins are involved in transmitting the regulatory actions of metabolic cues on pubertal maturation. Intracellular metabolic sensors, such as the AMP-activated protein kinase and the fuel-sensing deacetylase SIRT1, have been shown to contribute to puberty. Further understanding of these signals and regulatory circuits will help uncover the intimacies of the central control of puberty, as well as how alterations in metabolic status, ranging from undernutrition to obesity, affect the pubertal process. Precocious puberty is rare and has a clear female predominance. Central precocious puberty (CPP) is diagnosed when premature activation of the hypothalamic-pituitary axis occurs. Its causes are heterogeneous, with alterations of the central nervous system being of special interest, and with environmental factors also playing a role in some cases. During the last decade, several mutations in different genes (including KISS1, KISS1R, MKRN3 and DLK1) that cause CPP have been discovered. Loss-of-function mutations in MKRN3 are the most common monogenic cause of CPP known to date. Here, we review and update what is known regarding the genotype-phenotype relationship in patients with CPP.
Topics: Female; Humans; Kisspeptins; Male; Melanocortins; Puberty, Precocious; Receptors, Kisspeptin-1; Sexual Maturation; Ubiquitin-Protein Ligases
PubMed: 33904190
DOI: 10.1111/jne.12979 -
European Journal of Endocrinology Sep 2023Several rare loss-of-function mutations of delta-like noncanonical notch ligand 1 (DLK1) have been described in non-syndromic children with familial central precocious...
BACKGROUND
Several rare loss-of-function mutations of delta-like noncanonical notch ligand 1 (DLK1) have been described in non-syndromic children with familial central precocious puberty (CPP).
OBJECTIVE
We investigated genetic abnormalities of DLK1 gene in a French cohort of children with idiopathic CPP. Additionally, we explored the pattern of DLK1 serum levels in patients with CPP and in healthy children at puberty, as well as in wild-type female mice.
PATIENTS AND METHODS
Genomic DNA was obtained from 121 French index cases with CPP. Automated sequencing of the coding region of the DLK1 gene was performed in all cases. Serum DLK1 levels were measured by enzyme linked immunosorbent assay (ELISA) in 209 individuals, including 191 with normal pubertal development and in female mice during postnatal pubertal maturation.
RESULTS
We identified 2 rare pathogenic DLK1 allelic variants: A stop gain variant (c.372C>A; p.Cys124X) and a start loss variant (c.2T>G; p.Met1?, or p.0) in 2 French girls with CPP. Mean serum DLK1 levels were similar between healthy children and idiopathic CPP children. In healthy individuals, DLK1 levels correlated with pubertal stage: In girls, DLK1 decreased between Tanner stages III and V, whereas in boys, DLK1 decreased between Tanner stages II and V (P = .008 and .016, respectively). Serum levels of Dlk1 also decreased in wild-type female mice.
CONCLUSIONS
Novel loss-of-function mutations in DLK1 gene were identified in 2 French girls with CPP. Additionally, we demonstrated a pattern of dynamic changes in circulating DLK1 serum levels in humans and mice during pubertal stages, reinforcing the role of this factor in pubertal timing.
Topics: Animals; Child; Female; Humans; Male; Mice; Alleles; Calcium-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Membrane Proteins; Mutation; Puberty, Precocious
PubMed: 37703313
DOI: 10.1093/ejendo/lvad129