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  1. Article ; Online: Low-polarity untargeted metabolomic profiling as a tool to gain insight into seminal fluid.

    Olesti, Eulalia / Boccard, Julien / Rahban, Rita / Girel, Sergey / Moskaleva, Natalia E / Zufferey, Fanny / Rossier, Michel F / Nef, Serge / Rudaz, Serge / González-Ruiz, Víctor

    Metabolomics : Official journal of the Metabolomic Society

    2023  Volume 19, Issue 6, Page(s) 53

    Abstract: Introduction: A decrease in sperm cell count has been observed along the last several decades, especially in the most developed regions of the world. The use of metabolomics to study the composition of the seminal fluid is a promising approach to gain ... ...

    Abstract Introduction: A decrease in sperm cell count has been observed along the last several decades, especially in the most developed regions of the world. The use of metabolomics to study the composition of the seminal fluid is a promising approach to gain access to the molecular mechanisms underlying this fact.
    Objectives: In the present work, we aimed at relating metabolomic profiles of young healthy men to their semen quality parameters obtained from conventional microscopic analysis.
    Methods: An untargeted metabolomics approach focusing on low- to mid-polarity compounds was used to analyze a subset of seminal fluid samples from a cohort of over 2700 young healthy men.
    Results: Our results show that a broad metabolic profiling comprising several families of compounds (including acyl-carnitines, steroids, and other lipids) can contribute to effectively distinguish samples provided by individuals exhibiting low or high absolute sperm counts.
    Conclusion: A number of metabolites involved in sexual development and function, signaling, and energy metabolism were highlighted as being distinctive of samples coming from either group, proving untargeted metabolomics as a promising tool to better understand the pathophysiological processes responsible for male fertility impairment.
    MeSH term(s) Humans ; Male ; Semen Analysis ; Semen/metabolism ; Metabolomics/methods ; Spermatozoa/metabolism ; Sperm Count
    Language English
    Publishing date 2023-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2250617-2
    ISSN 1573-3890 ; 1573-3882
    ISSN (online) 1573-3890
    ISSN 1573-3882
    DOI 10.1007/s11306-023-02020-y
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    Zs.A 6361: Show issues Location:
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  2. Article ; Online: Gonadotropin axis and semen quality in young Swiss men after cannabis consumption: Effect of chronicity and modulation by cannabidiol.

    Zufferey, Fanny / Buitrago, Elina / Rahban, Rita / Senn, Alfred / Stettler, Eric / Rudaz, Serge / Nef, Serge / Donzé, Nicolas / Thomas, Aurélien / Rossier, Michel F

    Andrology

    2023  Volume 12, Issue 1, Page(s) 56–67

    Abstract: Background: While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level ... ...

    Abstract Background: While cannabis is the most widely used recreational drug in the world, the effects of phytocannabinoids on semen parameters and reproductive hormones remain controversial. Cannabinoid receptors are activated by these compounds at each level of the hypothalamus-pituitary-gonadotropic axis.
    Objectives: To assess the impact of the consumption of Δ-9-tetrahydrocannabinol and cannabidiol on semen parameters, as well as on male reproductive hormone and endocannabinoid levels, in a cohort of young Swiss men.
    Materials and methods: The individuals in a Swiss cohort were divided according to their cannabis consumption. In the cannabis user group, we determined the delay between the last intake of cannabis and sample collection, the chronicity of use and the presence of cannabidiol in the consumed product. Urinary Δ-9-tetrahydrocannabinol metabolites were quantified via gas chromatography-mass spectrometry. Blood phytocannabinoids, endocannabinoids and male steroids were determined via liquid chromatography-mass spectrometry/mass spectrometry, and other hypothalamus-pituitary-gonadotropic axis hormones were determined via immunoassays. Semen parameters such as sperm concentration and motility were recorded using computer-assisted sperm analysis.
    Results: Anandamide, N-palmitoyl ethanolamide, androgens, estradiol and sex hormone binding globulin levels were all higher in cannabis users, particularly in chronic, recent and cannabidiol-positive consumers. Gonadotropin levels were not significantly different in these user subpopulations, whereas prolactin and albumin concentrations were lower. In addition, cannabis users had a more basic semen pH and a higher percentage of spermatozoa with progressive motility. However, the two latter observations seem to be related to a shorter period of sexual abstinence in this group rather than to the use of cannabis.
    Conclusions: Because both cannabidiol and Δ-9-tetrahydrocannabinol are frequently used by men of reproductive age, it is highly relevant to elucidate the potential effects they may have on human reproductive health. This study demonstrates that the mode of cannabis consumption must be considered when evaluating the effect of cannabis on semen quality.
    MeSH term(s) Humans ; Male ; Semen Analysis ; Cannabis ; Cannabidiol/pharmacology ; Dronabinol/pharmacology ; Switzerland ; Seeds ; Prolactin
    Chemical Substances Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S) ; Prolactin (9002-62-4)
    Language English
    Publishing date 2023-04-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2696108-8
    ISSN 2047-2927 ; 2047-2919
    ISSN (online) 2047-2927
    ISSN 2047-2919
    DOI 10.1111/andr.13440
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    Zs.A 6983: Show issues Location:
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  3. Article ; Online: Semen endocannabinoids are correlated to sperm quality in a cohort of 200 young Swiss men.

    Zufferey, Fanny / Donzé, Nicolas / Rahban, Rita / Senn, Alfred / Stettler, Eric / Rudaz, Serge / Nef, Serge / Rossier, Michel F

    Andrology

    2020  Volume 8, Issue 5, Page(s) 1126–1135

    Abstract: Background: A role for endocannabinoids in the male and female reproductive systems has been highlighted during the recent decades. Some of these compounds bind the cannabinoid CB1 receptor, which is abundantly expressed in the central nervous system ... ...

    Abstract Background: A role for endocannabinoids in the male and female reproductive systems has been highlighted during the recent decades. Some of these compounds bind the cannabinoid CB1 receptor, which is abundantly expressed in the central nervous system but also present in the reproductive system, while others act as 'entourage compounds' modulators.
    Objectives: The present study aimed at evaluating the relationship between sperm quality and endocannabinoid profiles in a cohort of 200 young Swiss men and whether the presence of specific xenobiotics could influence these profiles.
    Materials and methods: Semen analysis was performed according to WHO guidelines. Endocannabinoid profiles in blood and semen, as well as bisphenol A and S in urine, were determined by LC-MSMS methods. The presence of selected drugs was tested in urine by immunological screening, and urinary tetrahydrocannabinol (THC) metabolites were quantified by GC-MS.
    Results: Anandamide concentrations in seminal fluid and oleoylethanolamide (OEA) concentrations in blood serum appeared inversely correlated with sperm motility, while semen palmytoylethanolamide (PEA) was positively linked to sperm concentration. Moreover, OEA and PEA in seminal fluid were associated with better sperm morphology. Interestingly, the concentrations of the same endocannabinoids measured in both blood and semen were not correlated, and the presence of THC metabolites in some individuals was linked to lower concentrations of endocannabinoids.
    Conclusions: In the context of the general decline of the sperm count observed within the male population, endocannabinoids in semen constitute a class of promising biochemical markers that open new perspectives as a complement for the usual evaluation of semen quality or for the toxicological screening of individuals' exposure to putative endocrine disruptors.
    Language English
    Publishing date 2020-04-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2696108-8
    ISSN 2047-2927 ; 2047-2919
    ISSN (online) 2047-2927
    ISSN 2047-2919
    DOI 10.1111/andr.12785
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  4. Article ; Online: In vitro models to study insulin and glucocorticoids modulation of trimethyltin (TMT)-induced neuroinflammation and neurodegeneration, and in vivo validation in db/db mice.

    Sandström, Jenny / Kratschmar, Denise V / Broyer, Alexandra / Poirot, Olivier / Marbet, Philippe / Chantong, Boonrat / Zufferey, Fanny / Dos Santos, Tania / Boccard, Julien / Chrast, Roman / Odermatt, Alex / Monnet-Tschudi, Florianne

    Archives of toxicology

    2019  Volume 93, Issue 6, Page(s) 1649–1664

    Abstract: Brain susceptibility to a neurotoxic insult may be increased in a compromised health status, such as metabolic syndrome. Both metabolic syndrome and exposure to trimethyltin (TMT) are known to promote neurodegeneration. In combination the two factors may ...

    Abstract Brain susceptibility to a neurotoxic insult may be increased in a compromised health status, such as metabolic syndrome. Both metabolic syndrome and exposure to trimethyltin (TMT) are known to promote neurodegeneration. In combination the two factors may elicit additive or compensatory/regulatory mechanisms. Combined effects of TMT exposure (0.5-1 μM) and mimicked metabolic syndrome-through modulation of insulin and glucocorticoid (GC) levels-were investigated in three models: tridimensional rat brain cell cultures for neuron-glia effects; murine microglial cell line BV-2 for a mechanistic analysis of microglial reactivity; and db/db mice as an in vivo model of metabolic syndrome. In 3D cultures, low insulin condition significantly exacerbated TMT's effect on GABAergic neurons and promoted TMT-induced neuroinflammation, with increased expression of cytokines and of the regulator of intracellular GC activity, 11β-hydroxysteroid dehydrogenase 1 (11β-Hsd1). Microglial reactivity increased upon TMT exposure in medium combining low insulin and high GC. These results were corroborated in BV-2 microglial cells where lack of insulin exacerbated the TMT-induced increase in 11β-Hsd1 expression. Furthermore, TMT-induced microglial reactivity seems to depend on mineralocorticoid receptor activation. In diabetic BKS db mice, a discrete exacerbation of TMT neurotoxic effects on GABAergic neurons was observed, together with an increase of interleukin-6 (IL-6) and of basal 11β-Hsd1 expression as compared to controls. These results suggest only minor additive effects of the two brain insults, neurotoxicant TMT exposure and metabolic syndrome conditions, where 11β-Hsd1 appears to play a key role in the regulation of neuroinflammation and of its protective or neurodegenerative consequences.
    MeSH term(s) 11-beta-Hydroxysteroid Dehydrogenase Type 1/biosynthesis ; 11-beta-Hydroxysteroid Dehydrogenase Type 1/drug effects ; Animals ; Cell Line ; Cells, Cultured ; Cytokines/biosynthesis ; Glucocorticoids/metabolism ; In Vitro Techniques ; Inflammation/chemically induced ; Inflammation/metabolism ; Insulin Secretion/drug effects ; Metabolic Syndrome/metabolism ; Mice ; Mice, Inbred Strains ; Nerve Degeneration/chemically induced ; Nerve Degeneration/metabolism ; Neuroglia/drug effects ; Neurons/drug effects ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucocorticoid/drug effects ; Reproducibility of Results ; Trimethyltin Compounds/toxicity
    Chemical Substances Cytokines ; Glucocorticoids ; Receptors, Glucocorticoid ; Trimethyltin Compounds ; trimethyltin (1631-73-8) ; 11-beta-Hydroxysteroid Dehydrogenase Type 1 (EC 1.1.1.146)
    Language English
    Publishing date 2019-04-16
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-019-02455-0
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    Uf I Zs.90: Show issues Location:
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  5. Article ; Online: Steroid profiles in both blood serum and seminal plasma are not correlated and do not reflect sperm quality: Study on the male reproductive health of fifty young Swiss men.

    Zufferey, Fanny / Rahban, Rita / Garcia, Arnaud / Gagnebin, Yoric / Boccard, Julien / Tonoli, David / Jeanneret, Fabienne / Stettler, Eric / Senn, Alfred / Nef, Serge / Rudaz, Serge / Rossier, Michel F

    Clinical biochemistry

    2018  Volume 62, Page(s) 39–46

    Abstract: Steroids play an important role in sperm production and quality. These hormones have been extensively studied in blood, but poorly investigated in semen. The purpose of our study was to evaluate the relationship between sperm quality and steroid profiles ...

    Abstract Steroids play an important role in sperm production and quality. These hormones have been extensively studied in blood, but poorly investigated in semen. The purpose of our study was to evaluate the relationship between sperm quality and steroid profiles in blood and semen in a small cohort of young Swiss men. Another objective was to determine whether the presence of xenobiotics or drugs could influence these profiles. Semen analysis was performed according to WHO guidelines, and steroid profiles in blood serum and seminal plasma were determined by two complementary approaches: a targeted investigation involving the quantification of a limited number of relevant steroids for testing putative correlations with sperm parameters and a global "steroidomic" analysis highlighting their complex metabolic relationship. Results showed that steroid profiles are distinct within blood and seminal fluid. No significant correlation was found between individual steroids measured in blood and in semen, demonstrating the relevance of assessing hormone levels in both fluids. Moreover, testosterone and androstenedione levels were significantly correlated in semen but not in blood. None of the evaluated spermiogram parameters was linked to steroid levels measured in any medium. The steroidomic analyses confirmed that the steroids present in both fluids are different and that there is no correlation with spermiogram parameters. Finally, upon toxicological screening, we observed that all the three samples positive for tetrahydrocannabinol, which is known to act as an endocrine disruptor, displayed low seminal testosterone concentrations. In conclusion, we did not find any evidence suggesting using steroid profiles, neither in blood nor in semen, as surrogates for sperm analyses. However, steroid profiles could be useful biomarkers of individual exposure to endocrine disruptors.
    MeSH term(s) Adolescent ; Adult ; Androstenedione/blood ; Androstenedione/metabolism ; Biomarkers/blood ; Biomarkers/metabolism ; Cluster Analysis ; Cohort Studies ; Dronabinol/analysis ; Endocrine Disruptors/analysis ; Environmental Monitoring/methods ; Humans ; Infertility, Male/blood ; Infertility, Male/diagnosis ; Infertility, Male/metabolism ; Infertility, Male/physiopathology ; Male ; Reproductive Health ; Semen/chemistry ; Semen/metabolism ; Semen Analysis ; Severity of Illness Index ; Steroids/blood ; Steroids/metabolism ; Switzerland ; Testosterone/blood ; Testosterone/metabolism ; Young Adult
    Chemical Substances Biomarkers ; Endocrine Disruptors ; Steroids ; Testosterone (3XMK78S47O) ; Androstenedione (409J2J96VR) ; Dronabinol (7J8897W37S)
    Language English
    Publishing date 2018-03-16
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 390372-2
    ISSN 1873-2933 ; 0009-9120
    ISSN (online) 1873-2933
    ISSN 0009-9120
    DOI 10.1016/j.clinbiochem.2018.03.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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