Endocrine Disruptors and Metabolic Changes: Impact on Puberty Control

Peralta, Marcela; Lizcano, Fernando

doi:10.1016/j.eprac.2024.01.006

Endocrine Practice

2024

DOI: 10.1016/j.eprac.2024.01.006

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Endocrine Disruptors and Metabolic Changes: Impact on Puberty Control

Marcela Peralta,

Fernando Lizcano

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2024

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Cited by 3 publications

References 220 publications

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Insights into pubertal development: a narrative review on the role of epigenetics

Shulhai,

Munerati,

Menzella

et al. 2024

J Endocrinol Invest

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Purpose Puberty is a key phase of growth and development, characterized by psychophysical transformations. It is driven by a combination of genetic, hormonal, and environmental variables. Epigenetic mechanisms, including histone post-translational modifications and chromatin remodeling, microRNAs, and DNA methylation, play important roles in orchestrating the developmental processes. We describe environmental factors that may interact with genetics, and factors influencing puberty onset, focusing in particular on epigenetic mechanisms that can help understand the timing and variations that lead to precocious or delayed puberty. Methods We conducted a narrative review of associations between puberty and epigenetic mechanisms through a comprehensive search of PubMed, Scopus, and Web of Science databases. Results The chromatin landscape of genes as KISS1 has revealed dynamic changes in histone modifications as puberty approaches, influencing the stimulation or inhibition of gene expression critical for reproductive maturation. MiRNAs regulate gene expression, whereas DNA methylation affects activation or repression of gene transcription of genes involved in pubertal timing. Moreover, studies in animal models have provided insights into the role of DNA methylation and miRNAs in brain sexual differentiation, highlighting the active involvement of epigenetic mechanisms in shaping sexually dimorphic brain structures. Conclusion This review highlights the importance of understanding the complex interplay between epigenetic regulation and pubertal development, which can lead to new therapeutic options and shed light on the fundamental processes driving reproductive maturation.

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Insights into pubertal development: a narrative review on the role of epigenetics

Shulhai,

Munerati,

Menzella

et al. 2024

J Endocrinol Invest

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Methylome analysis in girls with idiopathic central precocious puberty

Palumbo,

Cirillo

et al. 2024

Clin Epigenet

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Background Genetic and environmental factors are implicated in many developmental processes. Recent evidence, however, has suggested that epigenetic changes may also influence the onset of puberty or the susceptibility to a wide range of diseases later in life. The present study aims to investigate changes in genomic DNA methylation profiles associated with pubertal onset analyzing human peripheral blood leukocytes from three different groups of subjects: 19 girls with central precocious puberty (CPP), 14 healthy prepubertal girls matched by age and 13 healthy pubertal girls matched by pubertal stage. For this purpose, the comparisons were performed between pre- and pubertal controls to identify changes in normal pubertal transition and CPP versus pre- and pubertal controls. Results Analysis of methylation changes associated with normal pubertal transition identified 1006 differentially methylated CpG sites, 86% of them were found to be hypermethylated in prepubertal controls. Some of these CpG sites reside in genes associated with the age of menarche or transcription factors involved in the process of pubertal development. Analysis of methylome profiles in CPP patients showed 65% and 55% hypomethylated CpG sites compared with prepubertal and pubertal controls, respectively. In addition, interestingly, our results revealed the presence of 43 differentially methylated genes coding for zinc finger (ZNF) proteins. Gene ontology and IPA analysis performed in the three groups studied revealed significant enrichment of them in some pathways related to neuronal communication (semaphorin and gustation pathways), estrogens action, some cancers (particularly breast and ovarian) or metabolism (particularly sirtuin). Conclusions The different methylation profiles of girls with normal and precocious puberty indicate that regulation of the pubertal process in humans is associated with specific epigenetic changes. Differentially methylated genes include ZNF genes that may play a role in developmental control. In addition, our data highlight changes in the methylation status of genes involved in signaling pathways that determine the migration and function of GnRH neurons and the onset of metabolic and neoplastic diseases that may be associated with CPP in later life.

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Genetically Determined Plasma Docosahexaenoic Acid Showed a Causal Association with Female Reproductive Longevity-Related Phenotype: A Mendelian Randomization Study

Gao,

Ying,

Sun

et al. 2024

Nutrients

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Background: Female reproductive aging remains irreversible. More evidence is needed on how polyunsaturated fatty acids (PUFAs) affect the female reproductive lifespan. Objectives: To identify and validate specific PUFAs that can influence the timing of menarche and menopause in women. Methods: We utilized a two-sample Mendelian randomization (MR) framework to evaluate the causal relationships between various PUFAs and female reproductive longevity, defined by age at menarche (AAM) and age at natural menopause (ANM). Our analyses leveraged summary statistics from four genome-wide association studies (GWASs) on the plasma concentrations of 10 plasma PUFAs, including 8866 to 121,633 European individuals and 1361 East Asian individuals. Large-scale GWASs for reproductive traits provided the genetic data of AAM and ANM from over 202,323 European females and 43,861 East Asian females. Causal effects were estimated by beta coefficients, representing, for each increase in the standard deviation (SD) of plasma PUFA concentration, the yearly increase in AAM or ANM. Replications, meta-analyses, and cross-ancestry effects were assessed to validate the inference. Conclusions: Higher plasma DHA was identified to be associated with delayed natural menopause without affecting menarche, offering a potential intervention target for extending reproductive longevity.

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Endocrine Disruptors and Metabolic Changes: Impact on Puberty Control

Cited by 3 publications

References 220 publications

Insights into pubertal development: a narrative review on the role of epigenetics

Insights into pubertal development: a narrative review on the role of epigenetics

Methylome analysis in girls with idiopathic central precocious puberty

Genetically Determined Plasma Docosahexaenoic Acid Showed a Causal Association with Female Reproductive Longevity-Related Phenotype: A Mendelian Randomization Study

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