Impact of non-ionising radiation of male fertility: a systematic review.

Exposure to non-ionizing radiation has become inevitable because people cannot escape sources of electromagnetic fields, such as Wi-Fi or cell phones. Among the mechanisms mentioned, the energy emitted by this non-ionizing radiation could cause heating which would have harmful effects on semen quality. The objective of our study was to carry out a systematic review of the literature concerning the impact of exposure to non-ionizing radiation from mobile phones (or other sources) on sperm parameters.

Subfertile patients underestimate their risk factors of reprotoxic exposure.

Background: Exposure of men and women to environmental reprotoxic agents is associated with impaired fertility and pregnancy rates after assisted reproductive treatment (ART). Nevertheless, such exposures are generally not systematically assessed in current practice before ART and subfertile men are generally less explored than women. Our objective was to study subfertile men and women's level of knowledge about reprotoxic agents, their perception of their own risk factors and the correlation between perceived and identified circumstances of exposure.

Nomograms for predicting adverse obstetric outcome in IVF pregnancy: A preliminary study.

Background: In a previous study, we showed that the obstetric complication rate after in vitro fertilization (IVF) pregnancy was 40%. The main objective of our study was to determine maternal prognosis factors that influence the IVF pregnancy outcome.

Methods: We conducted an observational retrospective monocentric study between January 2014 and January 2018.

Assessment of a Screening Questionnaire to Identify Exposure to Lead in Pregnant Women.

Lead readily crosses the placenta and displays adverse effects on birth outcomes and neurodevelopment. Systematic identification of the risk of exposure during pregnancy is essential but rarely performed, probably due to hospital staff's workload and their lack of awareness. We aimed to evaluate the relevance of a questionnaire to screen pregnant women for lead exposure.

[Focus on the endocannabinoid system and the reprotoxicity of marijuana in female users].

Among recreative compounds, marijuana is the most used worldwide. Delta9THC binding on brain endocannabinoid receptors drives its psychotropic effects. The endocannabinoid system (ECS) is an endogenous neurohormonal system essential for homeostasis composed of ligands, metabolic enzymes and at least 2 receptors discovered to date.

Environmental Health in Perinatal and Early Childhood: Awareness, Representation, Knowledge and Practice of Southern France Perinatal Health Professionals.

The exposure of adults of reproductive age as well as pregnant women and children to environmental contaminants is of particular concern, as it can impact fertility, in utero development, pregnancy outcomes and child health. Consequently, the World Health Organisation (WHO) and international societies advocate including Environmental Health (EH) in perinatal care, yet perinatal health professionals (HPs) hardly put these recommendations into practice. In 2017, a cross-sectional study was performed in a large panel of perinatal HPs in south-eastern France with the aim of painting a picture of their current attitudes, representation, knowledge, and training expectations.

Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.

Although the precise signaling mechanisms underlying the vulnerability of some sub-populations of motoneurons in ALS remain unclear, critical factors such as metallo-proteinase 9 expression, neuronal activity and endoplasmic reticulum stress have been shown to be involved. In the context of SOD1(G93A) ALS mouse model, we previously showed that a two-fold decrease in calreticulin (CRT) is occurring in the vulnerable fast motoneurons. Here, we asked to which extent the decrease in CRT levels was causative to muscle denervation and/or motoneuron degeneration.

Somatic and axonal LIGHT signaling elicit degenerative and regenerative responses in motoneurons, respectively.

A receptor-ligand interaction can evoke a broad range of biological activities in different cell types depending on receptor identity and cell type-specific post-receptor signaling intermediates. Here, we show that the TNF family member LIGHT, known to act as a death-triggering factor in motoneurons through LT-βR, can also promote axon outgrowth and branching in motoneurons through the same receptor. LIGHT-induced axonal elongation and branching require ERK and caspase-9 pathways.

A rare motor neuron deleterious missense mutation in the DPYSL3 (CRMP4) gene is associated with ALS.

The dihydropyrimidinase-like 3 (DPYSL3) or Collapsin Response Mediator Protein 4a (CRMP4a) expression is modified in neurodegeneration and is involved in several ALS-associated pathways including axonal transport, glutamate excitotoxicity, and oxidative stress. The objective of the study was to analyze CRMP4 as a risk factor for ALS. We analyzed the DPYSL3/CRMP4 gene in French ALS patients (n = 468) and matched-controls (n = 394).

Reduced calreticulin levels link endoplasmic reticulum stress and Fas-triggered cell death in motoneurons vulnerable to ALS.

Cellular responses to protein misfolding are thought to play key roles in triggering neurodegeneration. In the mutant superoxide dismutase (mSOD1) model of amyotrophic lateral sclerosis (ALS), subsets of motoneurons are selectively vulnerable to degeneration. Fast fatigable motoneurons selectively activate an endoplasmic reticulum (ER) stress response that drives their early degeneration while a subset of mSOD1 motoneurons show exacerbated sensitivity to activation of the motoneuron-specific Fas/NO pathway.

Olesoxime delays muscle denervation, astrogliosis, microglial activation and motoneuron death in an ALS mouse model.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. The pathology is mimicked to a striking degree in transgenic mice carrying familial ALS-linked SOD1 gene mutations. Olesoxime (TRO19622), a novel neuroprotective and reparative compound identified in a high-throughput screen based on motoneuron (MN) survival, delays disease onset and improves survival in mutant SOD1(G93A) mice, a model for ALS.

α-Secretase-derived fragment of cellular prion, N1, protects against monomeric and oligomeric amyloid β (Aβ)-associated cell death.

In physiological conditions, both β-amyloid precursor protein (βAPP) and cellular prion (PrP(c)) undergo similar disintegrin-mediated α-secretase cleavage yielding N-terminal secreted products referred to as soluble amyloid precursor protein-α (sAPPα) and N1, respectively. We recently demonstrated that N1 displays neuroprotective properties by reducing p53-dependent cell death both in vitro and in vivo. In this study, we examined the potential of N1 as a neuroprotector against amyloid β (Aβ)-mediated toxicity.

Optimised and rapid pre-clinical screening in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS).

The human SOD1(G93A) transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS). In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease.

Enhanced neuronal Met signalling levels in ALS mice delay disease onset.

Signalling by receptor tyrosine kinases (RTKs) coordinates basic cellular processes during development and in adulthood. Whereas aberrant RTK signalling can lead to cancer, reactivation of RTKs is often found following stress or cell damage. This has led to the common belief that RTKs can counteract degenerative processes and so strategies to exploit them for therapy have been extensively explored.

The alpha-secretase-derived N-terminal product of cellular prion, N1, displays neuroprotective function in vitro and in vivo.

Cellular prion protein (PrP(c)) undergoes a disintegrin-mediated physiological cleavage, generating a soluble amino-terminal fragment (N1), the function of which remained unknown. Recombinant N1 inhibits staurosporine-induced caspase-3 activation by modulating p53 transcription and activity, whereas the PrP(c)-derived pathological fragment (N2) remains biologically inert. Furthermore, N1 protects retinal ganglion cells from hypoxia-induced apoptosis, reduces the number of terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling-positive and p53-immunoreactive neurons in a pressure-induced ischemia model of the rat retina and triggers a partial recovery of b-waves but not a-waves of rat electroretinograms.

Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease.

Mutations of the ubiquitin ligase parkin account for most autosomal recessive forms of juvenile Parkinson's disease (AR-JP). Several studies have suggested that parkin possesses DNA-binding and transcriptional activity. We report here that parkin is a p53 transcriptional repressor.

Loss of function of DJ-1 triggered by Parkinson's disease-associated mutation is due to proteolytic resistance to caspase-6.

DJ-1 was recently identified as a gene product responsible for a subset of familial Parkinson's disease (PD). The mechanisms by which mutations in DJ-1 alter its function and account for PD-related pathology remained largely unknown. We show that DJ-1 is processed by caspase-6 and that the caspase-6-derived C-terminal fragment of DJ-1 fully accounts for associated p53-dependent cell death.

p53-Dependent transcriptional control of cellular prion by presenilins.

The presenilin-dependent gamma-secretase processing of the beta-amyloid precursor protein (betaAPP) conditions the length of the amyloid beta peptides (Abeta) that accumulate in the senile plaques of Alzheimer's disease-affected brains. This, together with an additional presenilin-mediated epsilon-secretase cleavage, generates intracellular betaAPP-derived fragments named amyloid intracellular domains (AICDs) that regulate the transcription of several genes. We establish that presenilins control the transcription of cellular prion protein (PrP(c)) by a gamma-secretase inhibitor-sensitive and AICD-mediated process.

Regulation of betaAPP and PrPc cleavage by alpha-secretase: mechanistic and therapeutic perspectives.

Alzheimer's disease (AD) is by far the most common form of dementia in the elderly and concerns one out of three individuals over 85. Like other neurodegenerative disorders such as Parkinson, Hungtington or prion diseases, AD is characterized by the formation of amyloid plaques in the central nervous system. In the brain of AD patients, the main component of these abnormal deposits is an aggregated form of the so-called amyloid beta-peptide (Abeta), which is produced from a large trans-membrane type-1 protein, the beta-amyloid precursor protein (betaAPP), by the sequential action of the beta- and gamma-secretases.

LRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein.

The trafficking of normal cellular prion protein (PrPC) is believed to control its conversion to the altered conformation (designated PrPSc) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrPC on neurons is rapidly and constitutively endocytosed by means of coated pits, a property dependent upon basic amino acids at its N-terminus. Here, we show that low-density lipoprotein receptor-related protein 1 (LRP1), which binds to multiple ligands through basic motifs, associates with PrPC during its endocytosis and is functionally required for this process.

The gamma/epsilon-secretase-derived APP intracellular domain fragments regulate p53.

Amyloid beta-peptide (Abeta), which plays a central role in Alzheimer Disease, is generated by presenilin-dependent and presenilin-independent gamma-secretase cleavages of beta-amyloid precursor protein (betaAPP). We report that the presenilins (PS1 and PS2) also regulate p53-associated cell death. Thus, we established that PS deficiency, catalytically inactive PS mutants, gamma-secretase inhibitors and betaAPP or APLP2 depletion reduced the expression and activity of p53, and lowered the transactivation of its promoter and mRNA levels.

M1 and M3 muscarinic receptors control physiological processing of cellular prion by modulating ADAM17 phosphorylation and activity.

The cellular prion protein (PrP(c)) undergoes a physiological processing yielding the N-terminal fragment referred to as N1, the production of which can be constitutive or protein kinase C regulated. We show that activation of endogenous muscarinic receptors by carbachol and by the M1-selective agonist AF267B increases N1 recovery in an atropine-sensitive manner, in mouse embryonic primary neurons. To identify the muscarinic receptor subtype involved, we used human embryonic kidney HEK293 (HEK) cells stably overexpressing M1, M2, M3, or M4 receptor subtype.

The C-terminal products of cellular prion protein processing, C1 and C2, exert distinct influence on p53-dependent staurosporine-induced caspase-3 activation.

The cellular prion protein (PrP(c)) undergoes various endopro-teolytic attacks within its N-terminal domain, leading to the production of C-terminal fragments (C) tethered to the plasma membrane and soluble N-terminal peptides (N). One of these cleavages occurs at position 110/111, thereby generating C1 and N1 products. We have reported that disintegrins ADAM-10, -9, and -17 participate either directly or indirectly to this proteolytic event.