High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring.

Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g.

Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo.

Valproic acid (VPA) has long been the most widely used antiepileptic drug (AED) for the treatment of epilepsy, bipolar psychiatric disorders, and migraine. However, long-term VPA treatment has several adverse effects on the male reproductive system notably on endocrine functions and/or spermatic parameters. In utero exposure of the fetus to VPA is well known to be associated with a higher risk of several congenital malformations including those of male reproductive organs.

Spatiotemporal trends in human semen quality.

Over the past four decades, studies of various designs have reported spatial and temporal trends in human semen quality. Several standardized-methodology studies in homogeneous populations that compare specific cities within a country or a continent provide clear evidence of geographical differences in sperm production, even over short distances within the same country. Human sperm production is widely believed to be declining over time, but evidence from the scientific literature is less clear.

Comprehensive Evaluation of Blood Plasma and Serum Sample Preparations for HRMS-Based Chemical Exposomics: Overlaps and Specificities.

Sample preparation of biological samples can have a substantial impact on the coverage of small molecules detectable using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). This initial step is particularly critical for the detection of externally derived chemicals and their metabolites (internal chemical exposome) generally present at trace levels. Hence, our objective was to investigate how blood sample preparation methods affect the detection of low-abundant chemicals and to propose alternative methods to improve the coverage of the internal chemical exposome.

MERTK-Mediated LC3-Associated Phagocytosis (LAP) of Apoptotic Substrates in Blood-Separated Tissues: Retina, Testis, Ovarian Follicles.

Timely and efficient elimination of apoptotic substrates, continuously produced during one's lifespan, is a vital need for all tissues of the body. This task is achieved by cells endowed with phagocytic activity. In blood-separated tissues such as the retina, the testis and the ovaries, the resident cells of epithelial origin as retinal pigmented epithelial cells (RPE), testis Sertoli cells and ovarian granulosa cells (GC) provide phagocytic cleaning of apoptotic cells and cell membranes.

Acetaminophen metabolism revisited using non-targeted analyses: Implications for human biomonitoring.

The analgesic paracetamol/acetaminophen (N-acetyl-4-aminophenol, APAP) is commonly used to relieve pain, fever and malaise. While sales have increased worldwide, a growing body of experimental and epidemiological evidence has suggested APAP as a possible risk factor for various health disorders in humans. To perform internal exposure-based risk assessment, the use of accurate and optimized biomonitoring methods is critical.

Combined RNA/tissue profiling identifies novel Cancer/testis genes.

Cancer/Testis (CT) genes are induced in germ cells, repressed in somatic cells, and derepressed in somatic tumors, where these genes can contribute to cancer progression. CT gene identification requires data obtained using standardized protocols and technologies. This is a challenge because data for germ cells, gonads, normal somatic tissues, and a wide range of cancer samples stem from multiple sources and were generated over substantial periods of time.

From Metabolomics to HRMS-Based Exposomics: Adapting Peak Picking and Developing Scoring for MS1 Suspect Screening.

The technological advances of cutting-edge high-resolution mass spectrometry (HRMS) have set the stage for a new paradigm for exposure assessment. However, some adjustments of the metabolomics workflow are needed before HRMS-based methods can detect the low-abundant exogenous chemicals in human matrixes. It is also essential to provide tools to speed up marker identifications.

Potential for Virus Endogenization in Humans through Testicular Germ Cell Infection: the Case of HIV.

Viruses have colonized the germ line of our ancestors on several occasions during evolution, leading to the integration in the human genome of viral sequences from over 30 retroviral groups and a few nonretroviruses. Among the recently emerged viruses infecting humans, several target the testis (e.g.

Dynamics of the transcriptional landscape during human fetal testis and ovary development.

Study Question: Which transcriptional program triggers sex differentiation in bipotential gonads and downstream cellular events governing fetal testis and ovary development in humans?

Summary Answer: The characterization of a dynamically regulated protein-coding and non-coding transcriptional landscape in developing human gonads of both sexes highlights a large number of potential key regulators that show an early sexually dimorphic expression pattern.

What Is Known Already: Gonadal sex differentiation is orchestrated by a sexually dimorphic gene expression program in XX and XY developing fetal gonads. A comprehensive characterization of its non-coding counterpart offers promising perspectives for deciphering the molecular events underpinning gonad development and for a complete understanding of the etiology of disorders of sex development in humans.

Author Correction: Characterisation and localisation of the endocannabinoid system components in the adult human testis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Autophagy and spermatozoa].

Spermiogenesis, the ultimate stage of spermatogenesis, is a process involving autophagy. At this stage, the acrosome is generated by vesicular fusion and most of the cytoplasm disappears. Autophagy, literally "eating oneself", allowing the elimination and replacement of proteins and nonfunctional organelles, ensures the recycling of cellular constituents and is a highly conserved cellular mechanism within eukaryotic cells.

Characterisation and localisation of the endocannabinoid system components in the adult human testis.

Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testis but there is little information on the ECS expression within the human testis. In this study we characterised the main components of the ECS by immunohistochemistry (IHC) on archived testis tissue samples from 15 patients, and by in silico analysis of existing transcriptome datasets from testicular cell populations.

Autophagy is increased in cryptorchid testis resulting in abnormal spermatozoa.

Autophagy is involved in spermatogenesis by regulating germ cell maturation. This catabolic process increases with hyperthermic conditions to prevent the accumulation of damaged organelles. Cryptorchidism is associated with impairment of germ cell maturation revealed by the presence of immature forms of sperm cells in ejaculates.

Perinatal Exposure to Glyphosate and a Glyphosate-Based Herbicide Affect Spermatogenesis in Mice.

Glyphosate is the most widely used herbicide in the world. Several studies have investigated the effects of glyphosate and glyphosate-based herbicides (GBHs) on male reproduction, but there is still little and conflicting evidence for its toxicity. In this study, we analyzed the effects of glyphosate, alone or in formula, on the male reproductive system.

The ReproGenomics Viewer: a multi-omics and cross-species resource compatible with single-cell studies for the reproductive science community.

Motivation: Recent advances in transcriptomics have enabled unprecedented insight into gene expression analysis at a single-cell resolution. While it is anticipated that the number of publications based on such technologies will increase in the next decade, there is currently no public resource to centralize and enable scientists to explore single-cell datasets published in the field of reproductive biology.

Results: Here, we present a major update of the ReproGenomics Viewer, a cross-species and cross-technology web-based resource of manually-curated sequencing datasets related to reproduction.

The GMO90+ Project: Absence of Evidence for Biologically Meaningful Effects of Genetically Modified Maize-based Diets on Wistar Rats After 6-Months Feeding Comparative Trial.

The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33% with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial.

Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders.

Several studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXRα antagonist.

Gestational exposure to chlordecone promotes transgenerational changes in the murine reproductive system of males.

Environmental factors can affect epigenetic events during germline reprogramming and impose distinctive transgenerational consequences onto the offspring. In this study, we examined the transgenerational effects of chlordecone (CD), an organochlorine insecticide with well-known estrogenic properties. We exposed pregnant mice to CD from embryonic day 6.

Seminal Simian Immunodeficiency Virus in Chronically Infected Cynomolgus Macaques Is Dominated by Virus Originating from Multiple Genital Organs.

The sexual transmission of viruses is responsible for the spread of multiple infectious diseases. Although the human immunodeficiency virus (HIV)/AIDS pandemic remains fueled by sexual contacts with infected semen, the origin of virus in semen is still unknown. In a substantial number of HIV-infected men, viral strains present in semen differ from the ones in blood, suggesting that HIV is locally produced within the genital tract.

New transcriptomic tools to understand testis development and functions.

The testis plays a central role in the male reproductive system - secreting several hormones including male steroids and producing male gametes. A complex and coordinated molecular program is required for the proper differentiation of testicular cell types and maintenance of their functions in adulthood. The testicular transcriptome displays the highest levels of complexity and specificity across all tissues in a wide range of species.

Phagocytosis by Sertoli Cells: Analysis of Main Phagocytosis Steps by Confocal and Electron Microscopy.

Sertoli cells were discovered in the seminiferous tubules by Enrico Sertoli in 1865 (Morgagni 7:31-33, 1865). Intense phagocytosis is, in the context of spermatogenesis cycle, morphologically the most noticeable function of Sertoli cells. In this chapter the major principles of phagocytosis machinery and its specificities in the seminiferous tubules will be briefly reviewed, guidelines of analysis of main phagocytosis steps by confocal and transmission electron microscopy will be described, and a simplified method to assess phagocytosis rate in routine experiments will be given.