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Human Reproduction (Oxford, England) Jan 2019Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and...
STUDY QUESTION
Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls?
SUMMARY ANSWER
We found some associations of altered pubertal timing in girls, but little evidence in boys.
WHAT IS KNOWN ALREADY
Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies.
STUDY DESIGN, SIZE, DURATION
Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Pregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers.
MAIN RESULTS AND THE ROLE OF CHANCE
In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben.
LIMITATIONS, REASONS FOR CAUTION
These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable.
WIDER IMPLICATIONS OF THE FINDINGS
This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Adult; Child; Cohort Studies; Cosmetics; Endocrine Disruptors; Female; Humans; Longitudinal Studies; Male; Maternal Exposure; Maternal-Fetal Exchange; Parabens; Phenols; Phthalic Acids; Pregnancy; Prenatal Exposure Delayed Effects; Sex Factors; Sexual Maturation; Time Factors; Young Adult
PubMed: 30517665
DOI: 10.1093/humrep/dey337 -
The Cochrane Database of Systematic... Jul 2005Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some... (Review)
Review
BACKGROUND
Crohn's disease in childhood is a chronic relapsing condition. Fifteen to forty per cent of children with Crohn's disease have growth retardation (Griffiths 1993a). Some treatment modalities including corticosteroids have been implicated in growth failure but it is thought mainly to be secondary to uncontrolled disease activity (Motil 1993; Markowitz 1993). Growth is fundamental to the practice of pediatrics, so by taking growth as the primary outcome measure we address issues important to both patients, their families and pediatricians.
OBJECTIVES
To evaluate the effectiveness of the different modalities available for the treatment of childhood Crohn's disease with regard to the reversal of growth failure and the promotion of normal growth.
SEARCH STRATEGY
Searches were made of the following databases using the Collaborative Review Group Search Strategy: EMBASE (1984-2004), MEDLINE (1966-2004), The Cochrane Central Register of Controlled Trials, The Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register and the Science Citation Index. Abstracts from the major gastrointestinal research meetings and references from published articles were also reviewed.
SELECTION CRITERIA
Randomized controlled trials pertaining to children less than 18 years of age with Crohn's disease were selected. Those with growth as an outcome measure were included in the review.
DATA COLLECTION AND ANALYSIS
Data extraction and assessment of the methodological quality of each trial was independently reviewed by two reviewers. Only one good quality randomized controlled trial was included in the review and therefore no statistical analysis was possible.
MAIN RESULTS
Three randomized controlled trials were identified. One was of good methodological quality (Markowitz 2000). This study looked at the use of 6-mercaptopurine (6-MP) as a steroid sparing agent. No difference in linear growth was observed between the intervention and placebo groups, although the total steroid dose received over the 18 month follow up period was reduced in the group receiving 6-MP. The two remaining randomized controlled trials (Sanderson 1987; Thomas 1993a) consider the use of enteral feeding versus corticosteroids for induction of remission, with height velocity standard deviation score at 6 months as an outcome measure. Although of less rigorous methodological quality, the results of these studies are discussed in detail in the review. In both studies height velocity standard deviation scores were significantly increased in the enteral feeding group compared with the corticosteroid group.
AUTHORS' CONCLUSIONS
In addition to these randomized controlled trials, a body of lower quality evidence does exist relevant to two other important interventions; the use of supplemental enteral nutrition (Morin 1980; Belli 1988; Israel 1995) and the judicious use of surgical interventions in pre-pubertal children with refractory disease (Alperstein 1985; Lipson 1990; McLain 1990). Newer treatments, such as infliximab, are now becoming more widely used and may offer advantages in promoting growth. These effects are as yet unstudied. This review highlights the need for large, multi centre studies of the different treatment options in paediatric Crohn's disease and the importance of standardised measurements of growth, such as height velocity standard deviation scores and height standard deviation scores as outcome measures.
Topics: Adrenal Cortex Hormones; Antimetabolites; Child; Crohn Disease; Enteral Nutrition; Growth Disorders; Humans; Mercaptopurine; Prednisolone; Randomized Controlled Trials as Topic
PubMed: 16034910
DOI: 10.1002/14651858.CD003873.pub2 -
World Journal of Gastroenterology Mar 2014Growth and nutritional status are important issues in paediatric inflammatory bowel disease (IBD). While linear growth is easy to assess, nutritional status is more... (Review)
Review
Growth and nutritional status are important issues in paediatric inflammatory bowel disease (IBD). While linear growth is easy to assess, nutritional status is more complicated, with reports often compromised by the use of simple measures, such as weight and the body mass index, to assess nutritional status rather than more appropriate and sophisticated techniques to measure body composition. This review is an update on what is currently known about nutritional status as determined by body composition in paediatric IBD. Further, this review will focus on the impact of biologics on growth in paediatric IBD. Significant lean mass deficits have been reported in children with IBD compared with controls, and there is evidence these deficits persist over time. Furthermore, data imply that gender differences exist in body composition, both at diagnosis and in response to treatment. With respect to growth improvements following treatment with biologics, there are conflicting data. While some studies report enhancement of growth, others do not. The relationship between disease severity, impaired growth and the requirement for biologics needs to be considered when interpreting these data. However, key features associated with improvements in growth appear to be successful clinical response to treatment, patients in early stages of puberty, and the presence of growth failure at the onset of treatment.
Topics: Adolescent; Antibodies, Monoclonal; Biological Products; Body Composition; Body Mass Index; Body Weight; Child; Colitis, Ulcerative; Crohn Disease; Female; Growth Disorders; Humans; Inflammatory Bowel Diseases; Infliximab; Male; Nutrition Therapy; Nutritional Status; Puberty; Sex Factors
PubMed: 24696604
DOI: 10.3748/wjg.v20.i12.3191 -
Frontiers in Endocrinology 2022Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH... (Review)
Review
Despite decades of experience, the diagnosis of growth hormone deficiency (GHD) remains challenging, especially in peripubertal children. Failure to respond to GH stimulation tests (GHSTs) is needed to confirm GHD, but long-standing controversies regarding the number of tests needed and the interpretation of GH peaks are still a matter of debate worldwide. Diagnostic workup is even more problematic in short children with slow growth and delayed sexual development: they often exhibit low GH peaks under GHST, which often normalize as puberty progresses. Consequently, this transient suboptimal response to GHST may result in GH overtreatment, carrying both health and economic concerns. Considering the complex and bound link between GH axis and sex steroids, the use of sex steroid priming prior to GHST might be helpful in peripubertal setting. However, its use is still controversial. There is no consensus regarding patient selection, timing, dose, and preparation of sex steroids. In this review, we aim to overview the use of sex steroid priming in clinical practice, highlighting the need to develop appropriate guidelines in order to overcome diagnostic pitfalls in peripubertal age.
Topics: Humans; Child; Human Growth Hormone; Dwarfism, Pituitary; Gonadal Steroid Hormones; Puberty; Hypopituitarism; Steroids
PubMed: 36523598
DOI: 10.3389/fendo.2022.1072271 -
Theranostics 2021Sertoli cells are essential regulators of testicular fate in the differentiating gonad; however, its role and underlying molecular mechanism of regulating testicular...
Sertoli cells are essential regulators of testicular fate in the differentiating gonad; however, its role and underlying molecular mechanism of regulating testicular development in prepubertal testes are poorly understood. Although several critical regulatory factors of Sertoli cell development and function have been identified, identifying extrinsic factors that regulate gonocyte proliferation and migration processes during neonatal testis development remains largely unknown. We used the Sertoli cell-specific conditional knockout strategy (Cre/Loxp) in mice and molecular biological analyses (Luciferase assay, ChIP-qPCR, RNA-Seq, etc.) in vitro and in vivo to study the physiological roles of hnRNPU in Sertoli cells on regulating testicular development in prepubertal testes. We identified a co-transcription factor, hnRNPU, which is highly expressed in mouse and human Sertoli cells and required for neonatal Sertoli cell and pre-pubertal testicular development. Conditional knockout of hnRNPU in murine Sertoli cells leads to severe testicular atrophy and male sterility, characterized by rapid depletion of both Sertoli cells and germ cells and failure of spermatogonia proliferation and migration during pre-pubertal testicular development. At molecular levels, we found that hnRNPU interacts with two Sertoli cell markers WT1 and SOX9, and enhances the expression of two transcriptional factors, and in Sertoli cells by directly binding to their promoter regions. Further RNA-Seq and bioinformatics analyses revealed the transcriptome-wide of key genes essential for Sertoli cell and germ cell fate control, such as biological adhesion, proliferation and migration, were deregulated in Sertoli cell-specific hnRNPU mutant testes. Our findings demonstrate an essential role of hnRNPU in Sertoli cells for prepubertal testicular development and testis microenvironment maintenance and define a new insight for our understanding of male infertility therapy.
Topics: Animals; Cell Differentiation; Gene Expression; Gene Expression Regulation; Heterogeneous-Nuclear Ribonucleoprotein U; Humans; Male; Mice; Mice, Inbred C57BL; SOX9 Transcription Factor; SOXE Transcription Factors; Sertoli Cells; Testis; Transcription Factors; Transcriptome; WT1 Proteins
PubMed: 34815802
DOI: 10.7150/thno.66819 -
The Journal of Veterinary Medical... May 2023Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical...
Cryptorchid bulls have low economic value owing to the effects of masculinization. Moreover, surgical removal of an ectopic testis is difficult in certain clinical cases. Recently, immunocastration has garnered popularity as a nonsurgical castration method in pig farming; however, the effects of immunocastration on cryptorchid bulls are yet to be yet. Herein, we investigated endocrine changes due to immunocastration in cryptorchid bulls and studied its effectiveness. This study included 13 Holstein bulls diagnosed with cryptorchidism and classified into two groups based on pubertal period: <8 months of age (pregroup) and ≥8 months of age (postgroup). Antigonadotropin-releasing hormone (GnRH) vaccine was used for immunocastration, and two vaccine doses were administered. Blood testosterone and anti-Müllerian hormone (AMH) levels were measured and analyzed for endocrine evaluation. The testosterone levels significantly decreased following the start of immunocastration in both groups, thereby confirming the efficacy of antiGnRH vaccination in cryptorchid bulls. The AMH levels significantly increased in the pregroup with two antiGnRH vaccination, suggesting a compensatory response via the neutralization of GnRH antibodies. The AMH levels did not significantly change in the postgroup, indicating the partial suppression of AMH secretion in Sertoli cells during sexual maturation and failure of Sertoli cell maturation. Thus, we successfully restrained the serum testosterone levels in cryptorchid bulls using antiGnRH vaccine. The testosterone levels are a useful indicator of the immunocastration effect on cryptorchid bulls. Hereafter, a vaccine program that can sustain the castration effect on cryptorchid bulls is necessary.
Topics: Male; Animals; Cattle; Swine; Gonadotropin-Releasing Hormone; Cryptorchidism; Testis; Testosterone; Vaccines; Cattle Diseases; Swine Diseases
PubMed: 36927961
DOI: 10.1292/jvms.22-0571 -
Frontiers in Endocrinology 2018Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels,... (Review)
Review
Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG) axis during the neonatal period, resulting in high gonadotropin and sex steroid levels, and occurs mainly in the first 3-6 months of life in both sexes. The rise in the levels of these hormones allows for the maturation of the sexual organs. In boys, the peak testosterone level is associated with penile and testicular growth and the proliferation of gonadic cells. In girls, the oestradiol levels stimulate breast tissue, but exhibit considerable fluctuations that probably reflect the cycles of maturation and atrophy of the ovarian follicles. Minipuberty allows for the development of the genital organs and creates the basis for future fertility, but further studies are necessary to understand its exact role, especially in girls. Nevertheless, no scientific study has yet elucidated how the HPG axis turns itself off and remains dormant until puberty. Additional future studies may identify clinical implications of minipuberty in selected cohorts of patients, such as premature and small for gestational age infants. Finally, minipuberty provides a fundamental 6-month window of the possibility of making early diagnoses in patients with suspected sexual reproductive disorders to enable the prompt initiation of treatment rather than delaying treatment until pubertal failure.
PubMed: 30093882
DOI: 10.3389/fendo.2018.00410 -
Molecular and Cellular Endocrinology Dec 2020Prenatal testosterone (T)- treated female sheep manifest juvenile insulin resistance, post-pubertal increase in insulin sensitivity and return to insulin resistance...
Prenatal testosterone (T)- treated female sheep manifest juvenile insulin resistance, post-pubertal increase in insulin sensitivity and return to insulin resistance during adulthood. Since compensatory hyperinsulinemia is associated with insulin resistance, altered pancreatic islet ontogeny may contribute towards metabolic defects. To test this, pregnant sheep were treated with or without T propionate from days 30-90 of gestation and pancreas collected from female fetuses at gestational day 90 and female offspring at 21 months-of-age. Uterine (maternal) and umbilical (fetal) arterial blood insulin/glucose ratios were determined at gestational day 90. The morphological and functional changes in pancreatic islet were assessed through detection of 1) islet hormones (insulin, glucagon) and apoptotic beta cells at fetal day 90 and 2) islet hormones (insulin, glucagon and somatostatin), and pancreatic lipid and collagen accumulation in adults. At gestational day 90, T-treatment led to maternal but not fetal hyperinsulinemia, decrease in pancreatic/fetal weight ratio and alpha cells, and a trend for increase in beta cell apoptosis in fetal pancreas. Adult prenatal T-treated female sheep manifested 1) significant increase in beta cell size and a tendency for increase in insulin and somatostatin stained area and proportion of beta cells in the islet; and 2) significant increase in pancreatic islet collagen and a tendency towards increased lipid accumulation. Gestational T-treatment induced changes in pancreatic islet endocrine cells during both fetal and adult ages track the trajectory of hyperinsulinemic status with the increase in adult pancreatic collagen accumulation indicative of impending beta cell failure with chronic insulin resistance.
Topics: Animals; Animals, Newborn; Apoptosis; Embryonic Development; Female; Fetus; Hyperandrogenism; Hyperinsulinism; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Pancreas; Pregnancy; Prenatal Exposure Delayed Effects; Sheep; Testosterone
PubMed: 32726642
DOI: 10.1016/j.mce.2020.110950 -
Environmental Health : a Global Access... Apr 2018The age of menarche has been associated with metabolic and cardiovascular disease, as well as cancer risk. The decline in menarcheal age over the past century may be...
BACKGROUND
The age of menarche has been associated with metabolic and cardiovascular disease, as well as cancer risk. The decline in menarcheal age over the past century may be partially attributable to increased exposure to endocrine disrupting chemicals (EDCs).
METHODS
We assessed the influence of 26 phenol and phthalate biomarkers on the timing of menarche in a longitudinal cohort of Chilean girls. These EDCs were quantified in urine collected prior to the onset of breast development (Tanner 1; B1), and during adolescence (Tanner 4; B4). Multivariable accelerated failure time (AFT) models were used to analyze associations between biomarker concentrations and the age of menarche adjusting for body mass index (BMI) Z-score and maternal education, accounting for within-subject correlation.
RESULTS
Several biomarkers were significantly associated with the age at menarche; however, these associations were dependent on the timing of biomarker assessment. A log(ng/ml) increase in B1 concentrations of di(2-ethylhexyl) phthalate biomarkers was associated with later menarche (hazard ratio (HR): 0.77; 95% CI: 0.60, 0.98), whereas higher B1 concentrations of 2,5-dichlorophenol and benzophenone-3 were associated with earlier menarche (HR: 1.13; 95% CI: 1.01, 1.27; HR: 1.17; 95% CI: 1.06, 1.29, respectively). Elevated B4 concentrations of monomethyl phthalate were similarly associated with earlier menarche (HR: 1.30; 95% CI: 1.10, 1.53). The impact of monoethyl phthalate and triclosan concentrations on pubertal timing were significantly modified by BMI Z-score. Higher monoethyl phthalate and triclosan concentrations were associated with earlier menarche among overweight or obese girls, but not among those that were normal weight.
CONCLUSIONS
This study identifies modulation of sexual maturation by specific EDC biomarkers in Latina girls.
Topics: Adolescent; Age Factors; Child; Chile; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Humans; Longitudinal Studies; Menarche; Phenols; Phthalic Acids; Sexual Maturation
PubMed: 29615064
DOI: 10.1186/s12940-018-0376-z -
Cureus Jan 2022It has been observed that 5% of adolescents are affected by pubertal timing disorders. However, there is limited data about this in Pakistan. This cross-sectional study...
INTRODUCTION
It has been observed that 5% of adolescents are affected by pubertal timing disorders. However, there is limited data about this in Pakistan. This cross-sectional study aimed to observe the patterns and causes of delayed puberty (DP) among patients presenting at the endocrine clinic of a tertiary care hospital in Karachi.
METHODS
This observational study was conducted at the endocrine clinic of Jinnah Postgraduate Medical Centre (JPMC) Unit II from 2007 to 2015. A detailed history was obtained from patients presenting with DP. We noted the available demographic data, main complaints, and family history of DP. Physical examinations were performed and the data recorded. Tanner staging was used to assess pubertal development. Relevant laboratory and imaging investigations were performed; data analysis was performed using SPSS 17 (IBM Corp., Armonk, NY).
RESULTS
A total of 2670 patients were registered in the endocrine clinic during the study period, of which 171 presented with DP; 119 were males and 52 were females. There was a wide variation in age at presentation ranging from 10 to 32 years. The majority of patients presented with short stature - 69 (57.98%) males and 19 (36.53%) females. Small testes were present in 28 patients (23.52%); 19 (15.96%) males presented with absent secondary sexual characteristics and infertility was present in three (2.54%) males, primary amenorrhea was observed in 25 (48.07%), both primary amenorrhea and short stature were the presenting symptoms of five (9.61%), and failure of breast development was seen in three (5.76%) females. Constitutional delayed growth and puberty (CDGP) was diagnosed in 42 patients (24.6%). The definitive diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) was made in 18 (10.5%) patients. In another 18 (10.5%) patients, we could not differentiate between CDGP and IHH. Functional hypogonadotropic hypogonadism (FHH) due to non-endocrine illness was present in 16 patients (9.4%). The cause of DP was hypogonadotropic hypogonadism in 33 (19.3%) patients whereas 44 patients presenting with DP could not be classified due to incomplete data.
CONCLUSION
This study showed that CDGP was the most common cause of DP in our patients with the most common presentation being short stature in males and amenorrhea in females. It is essential to differentiate CDGP in children from a small fraction of the pathological and treatable causes of DP.
PubMed: 35228933
DOI: 10.7759/cureus.21574