Impact of antenatal exposure to a mixture of persistent organic pollutants on intellectual development.

Objective: Strong experimental evidence exists that several endocrine disrupting chemicals (EDCs) have neurobehavioral toxicity. However, evidence of associations between prenatal exposure and child's cognitive development is inconsistent. Moreover, toxicants are generally analyzed one by one without considering aggregate effects.

Enhanced identification of endocrine disruptors through integration of science-based regulatory practices and innovative methodologies: The MERLON Project.

The prevalence of hormone-related health issues caused by exposure to endocrine disrupting chemicals (EDCs) is a significant, and increasing, societal challenge. Declining fertility rates together with rising incidence rates of reproductive disorders and other endocrine-related diseases underscores the urgency in taking more action. Addressing the growing threat of EDCs in our environment demands robust and reliable test methods to assess a broad variety of endpoints relevant for endocrine disruption.

[Congenital hyperinsulinism : contributions of chemistry, therapeutic response, genetics and imaging].

Congenital hyperinsulinism is the most common cause of recurrent hypoglycemia in newborns and children. Early diagnosis and rapid management are essential to avoid hypoglycaemic brain injury and later neurological complications. Management of those patients involves biological evaluation, molecular genetics, imaging techniques and surgical advances.

Near adult height and BMI changes in growth hormone treated short children with Noonan syndrome: the Belgian experience.

Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al.

Emulsifiers during gestation: The risks of ultra-processed food revealed in mice.

Several dietary components disrupt the control of energy balance. A new study in PLOS Biology shows that, in mice, maternal consumption of emulsifiers induces a rewiring of the hypothalamic feeding circuits and causes neuropsychological impairment in the offspring.

Perinatal exposure to the fungicide ketoconazole alters hypothalamic control of puberty in female rats.

Introduction: Estrogenic endocrine disrupting chemicals (EDCs) such as diethylstilbestrol (DES) are known to alter the timing of puberty onset and reproductive function in females. Accumulating evidence suggests that steroid synthesis inhibitors such as ketoconazole (KTZ) or phthalates may also affect female reproductive health, however their mode of action is poorly understood. Because hypothalamic activity is very sensitive to sex steroids, we aimed at determining whether and how EDCs with different mode of action can alter the hypothalamic transcriptome and GnRH release in female rats.

Unusual Cardiac Manifestations of a Pheochromocytoma in a Girl.

We report the case of an 11-year-old girl who complained about severe asthenia, orthostatic dizziness and abdominal pain for 4 weeks. The primary investigation concluded on febrile urinary tract infection treated by antibiotics. Symptom persistence prompted cardiological and endocrinological investigations.

Male minipuberty involves the gonad-independent activation of preoptic nNOS neurons.

Background: The maturation of the hypothalamic-pituitary-gonadal (HPG) axis is crucial for the establishment of reproductive function. In female mice, neuronal nitric oxide synthase (nNOS) activity appears to be key for the first postnatal activation of the neural network promoting the release of gonadotropin-releasing hormone (GnRH), i.e.

Exposure to the pesticides linuron, dimethomorph and imazalil alters steroid hormone profiles and gene expression in developing rat ovaries.

Inhibition of androgen signaling during critical stages of ovary development can disrupt folliculogenesis with potential consequences for reproductive function later in life. Many environmental chemicals can inhibit the androgen signaling pathway, which raises the question if developmental exposure to anti-androgenic chemicals can negatively impact female fertility. Here, we report on altered reproductive hormone profiles in prepubertal female rats following developmental exposure to three pesticides with anti-androgenic potential: linuron (25 and 50 mg/kg bw/d), dimethomorph (60 and 180 mg/kg bw/d) and imazalil (8 and 24 mg/kg bw/d).

Induction of Oxidative Stress and Alteration of Synaptic Gene Expression in Newborn Hippocampal Granule Cells after Developmental Exposure to Aroclor 1254.

Introduction: Hippocampal newborn neurons integrate into functional circuits where they play an important role in learning and memory. We previously showed that perinatal exposure to Aroclor 1254, a commercial mixture of polychlorinated biphenyls (PCBs) associated with alterations of cognitive function in children, disrupted the normal maturation of excitatory synapses in the dentate gyrus. We hypothesized that hippocampal immature neurons underlie some of the cognitive effects of PCBs.

GnRH neurons recruit astrocytes in infancy to facilitate network integration and sexual maturation.

Neurons that produce gonadotropin-releasing hormone (GnRH), which control fertility, complete their nose-to-brain migration by birth. However, their function depends on integration within a complex neuroglial network during postnatal development. Here, we show that rodent GnRH neurons use a prostaglandin D receptor DP1 signaling mechanism during infancy to recruit newborn astrocytes that 'escort' them into adulthood, and that the impairment of postnatal hypothalamic gliogenesis markedly alters sexual maturation by preventing this recruitment, a process mimicked by the endocrine disruptor bisphenol A.

Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect.

Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERβ- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role. Twenty children and young adults (seven females and 13 males) with a median age of 13.

Endocrine-disrupting chemicals and their effects on puberty.

Sexual maturation in humans is characterized by a unique individual variability. Pubertal onset is a highly heritable polygenic trait but it is also affected by environmental factors such as obesity or endocrine disrupting chemicals. The last 30 years have been marked by a constant secular trend toward earlier age at onset of puberty in girls and boys around the world.

Perinatal exposure to known endocrine disrupters alters ovarian development and systemic steroid hormone profile in rats.

Disrupted ovarian development induced by chemical exposure may impair fertility later in life. Since androgens are essential for early ovarian development, we speculated that perinatal exposure to a binary mixture of the known anti-androgens DEHP and procymidone could alter steroid synthesis, disrupt ovarian follicle recruitment and ultimately maturation in female rat offspring. Wistar rat dams were exposed by oral gavage from gestation day 7 to postnatatal day 22 to two mixture doses known to alter reproductive development in male offspring (low: 10 mg/kg bw/day of procymidone and 30 mg/kg bw/day of DEHP; high: 20 mg/kg bw/day of procymidone and 60 mg/kg bw/day of DEHP).

A Putative Adverse Outcome Pathway Network for Disrupted Female Pubertal Onset to Improve Testing and Regulation of Endocrine Disrupting Chemicals.

The average age for pubertal onset in girls has declined over recent decades. Epidemiological studies in humans and experimental studies in animals suggest a causal role for endocrine disrupting chemicals (EDCs) that are present in our environment. Of concern, current testing and screening regimens are inadequate in identifying EDCs that may affect pubertal maturation, not least because they do not consider early-life exposure.

Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals-The FREIA Project.

Currently available test methods are not well-suited for the identification of chemicals that disturb hormonal processes involved in female reproductive development and function. This renders women's reproductive health at increasing risk globally, which, coupled with increasing incidence rates of reproductive disorders, is of great concern. A woman's reproductive health is largely established during embryonic and fetal development and subsequently matures during puberty.

Persistent vs Transient Alteration of Folliculogenesis and Estrous Cycle After Neonatal vs Adult Exposure to Bisphenol A.

Exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is known to produce variable effects on female puberty and ovulation. This variability of effects is possibly due to differences in dose and period of exposure. Little is known about the effects of adult exposure to environmentally relevant doses of this EDC and the differences in effect after neonatal exposure.

Endocrine disrupters and possible contribution to pubertal changes.

The onset of puberty strongly depends on organizational processes taking place during the fetal and early postnatal life. Therefore, exposure to environmental pollutants such as Endocrine disrupting chemicals (EDCs) during critical periods of development can result in delayed/advanced puberty and long-term reproductive consequences. Human evidence of altered pubertal timing after exposure to endocrine disrupting chemicals is equivocal.

Compound heterozygous mutations in the luteinizing hormone receptor signal peptide causing 46,XY disorder of sex development.

Testosterone production by the fetal testis depends on a functional relationship between hCG and the LH/chorionic gonadotropin receptor (LHCGR). Failure of the receptor to correctly respond to its ligand leads to impaired sexual differentiation in males. A phenotypically female patient with pubertal delay had a 46,XY karyotype and was diagnosed with 46,XY disorder of sex development (DSD).

Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against .

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene () have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of mice against , a pathogen carrying T-independent antigens.

Rationale for Environmental Hygiene towards global protection of fetuses and young children from adverse lifestyle factors.

Background: The regulatory management of chemicals and toxicants in the EU addresses hundreds of different chemicals and health hazards individually, one by one. An issue is that, so far, the possible interactions among chemicals or hazards are not considered as such. Another issue is the anticipated delay of several decades before effective protection of public health by regulatory decisions due to a time consuming process.

Neuroendocrine disruption without direct endocrine mode of action: Polychloro-biphenyls (PCBs) and bisphenol A (BPA) as case studies.

Endocrine disruption is commonly thought to be restricted to a direct endocrine mode of action i.e. the perturbation of the activation of a given type of hormonal receptor by its natural ligand.