Endocrine-disrupting chemicals and their effects on puberty

López-Rodríguez, David; Franssen, Delphine; Heger, Sabine

doi:10.1016/j.beem.2021.101579

Cited by 38 publications

(28 citation statements)

References 111 publications

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“…It is interesting that females were resistant to NeuroMix effects on development, with no change in body weight or puberty. The lack of effect on the timing of puberty was surprising, as the mixture contains estrogenic EDCs previously shown to advance the timing of puberty [ 91 , 92 ]. It is likely that the presence of EDCs with anti-androgenic effects or other hormonal mechanisms that interact with the effects of estrogens may have counteracted these actions.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Gore

Moore

Groom

et al. 2022

Toxics

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Humans and wildlife are exposed to endocrine-disrupting chemicals (EDCs) throughout their lives. Environmental EDCs are implicated in a range of diseases/disorders with developmental origins, including neurodevelopment and behavior. EDCs are most often studied one by one; here, we assessed outcomes induced by a mixture designed to represent the real-world situation of multiple simultaneous exposures. The choice of EDCs, which we refer to as “NeuroMix,” was informed by evidence for neurobiological effects in single-compound studies and included bisphenols, phthalates, vinclozolin, and perfluorinated, polybrominated, and polychlorinated compounds. Pregnant Sprague Dawley rats were fed the NeuroMix or vehicle, and then offspring of both sexes were assessed for effects on postnatal development and behaviors and gene expression in the brain in adulthood. In order to determine whether early-life EDCs predisposed to subsequent vulnerability to postnatal life challenges, a subset of rats were also given a stress challenge in adolescence. Prenatal NeuroMix exposure decreased body weight and delayed puberty in males but not females. In adulthood, NeuroMix caused changes in anxiety-like, social, and mate preference behaviors only in females. Effects of stress were predominantly observed in males. Several interactions of NeuroMix and stress were found, especially for the mate preference behavior and gene expression in the brain. These findings provide novel insights into how two realistic environmental challenges lead to developmental and neurobehavioral deficits, both alone and in combination, in a sex-specific manner.

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Section: Discussionmentioning

confidence: 99%

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Gore

Moore

Groom

et al. 2022

Toxics

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“…In addition to its monogenic etiology, obesity (14) and environmental endocrine disrupting chemicals (EDCs) (15) are currently considered to be the main causes of CPP. EDCs could regulate the activation of either gonadotropin-releasing hormone (GnRH) neurons or gonadal steroidogenesis in order to initiate puberty through epigenetic mechanisms (16). Recently, Heras et al (17) revealed that linking kisspeptin, hypothalamic paraventricular nucleus (PVN) ceramide synthesis and sympathetic innervation in the rat ovary were key to obesity-induced pubertal precocity.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of proteomics and metabolomics in girls with central precocious puberty

Lan

Chen

2022

Front. Endocrinol.

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BackgroundCentral precocious puberty (CPP) is a multifactorial and complex condition. Traditional studies focusing on a single indicator cannot always elucidate this panoramic condition but these may be revealed by using omics techniques.ObjectiveProteomics and metabolomics analysis of girls with CPP were compared to normal controls and the potential biomarkers and pathways involved were explored.MethodsSerum proteins and metabolites from normal girls and those with CPP were compared by LC-MS/MS. Multivariate and univariate statistical analysis were used to identify the differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs). Functional annotation and pathway enrichment analysis were performed by using GO and KEGG databases, and candidate markers were screened. Finally, bioinformatic analysis was used to integrate the results of proteomics and metabolomics to find the key differential proteins, metabolites and potential biomarkers of CPP.Results134 DEPs were identified in girls with CPP with 71 up- and 63 down-regulated, respectively. Up-regulated proteins were enriched mainly in the extracellular matrix, cell adhesion and cellular protein metabolic processes, platelet degranulation and skeletal system development. The down-regulated proteins were mainly enriched in the immune response. Candidate proteins including MMP9, TIMP1, SPP1, CDC42, POSTN, COL1A1, COL6A1, COL2A1 and BMP1, were found that may be related to pubertal development. 103 DEMs were identified, including 42 up-regulated and 61 down-regulated metabolites which were mainly enriched in lipid and taurine metabolic pathways. KGML network analysis showed that phosphocholine (16:1(9Z)/16:1(9Z)) was involved in arachidonic acid, glycerophospholipid, linoleic acid and α-linolenic acid metabolism and it may be used as a biomarker of CPP.ConclusionsOur study is the first to integrate proteomics and metabolomics to analyze the serum of girls with CPP and we found some key differential proteins and metabolites as well as a potential biomarker for this condition. Lipid metabolism pathways are involved and these may provide a key direction to further explore the molecular mechanisms and pathogenesis of CPP.

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“…Endocrines 2022, 3 434 Specific environmental agents, known as endocrine disrupting chemicals (EDCs) are known to affect the HPG axis from the prenatal period throughout life. There are many proposed mechanisms of their actions, such as interference with the cellular organization of the hypothalamus including the molecular and cellular function of the GnRH neurons, and long-lasting epigenetic changes [11]. At a population level and in various cohort studies, some EDCs such as bisphenol A (BPA) and phthalates have been speculated to have estrogen-like properties and, hence, can cause precocious puberty in females and delayed puberty in males [12,13].…”

Section: Introductionmentioning

confidence: 99%

The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs)

Mucci

Clemente

2022

Endocrines

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Despite the growing prevalence of central precocious puberty (CPP), most cases are still diagnosed as “idiopathic” due to the lack of identifiable findings of other diagnostic etiology. We are gaining greater insight into some key genes affecting neurotransmitters and receptors and how they stimulate or inhibit gonadotropin-releasing hormone (GnRH) secretion, as well as transcriptional and epigenetic influences. Although the genetic contributions to pubertal regulation are more established in the hypogonadotropic hypogonadism (HH) literature, cases of CPP have provided the opportunity to learn more about its own genetic influences. There have been clinically confirmed cases of CPP associated with gene mutations in kisspeptin and its receptor (KISS1, KISS1R), Delta-like noncanonical Notch ligand 1 (DLK1), and the now most commonly identified genetic cause of CPP, makorin ring finger protein (MKRN3). In addition to these proven genetic causes, a number of other candidates continue to be evaluated. After reviewing the basic clinical aspects of puberty, we summarize what is known about the various genetic and epigenetic causes of CPP as well as discuss some of the potential effects of endocrine disrupting chemicals (EDCs) on some of these processes.

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Endocrine-disrupting chemicals and their effects on puberty

Cited by 38 publications

References 111 publications

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Prenatal Exposure to an EDC Mixture, NeuroMix: Effects on Brain, Behavior, and Stress Responsiveness in Rats

Integrated analysis of proteomics and metabolomics in girls with central precocious puberty

The Role of Genetics in Central Precocious Puberty: Confirmed and Potential Neuroendocrine Genetic and Epigenetic Contributors and Their Interactions with Endocrine Disrupting Chemicals (EDCs)

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