Tribbles expression in cumulus cells is related to oocyte maturation and fatty acid metabolism.

International audienceIn mammals, the Tribbles family includes widely expressed serine-threonine kinase-like proteins (TRIB1, TRIB2 and TRIB3) that are involved in multiple biological processes including cell proliferation and fatty acid (FA) metabolism. Our recent studies highlighted the importance of FA metabolism in cumulus cells (CC) during oocyte maturation in vertebrates and reported a higher TRIB1 expression in CC surrounding in vivo mature oocytes as compared to immature ooocytes in mice and cows. The objective was to investigate Tribbles expression patterns in bovine CC during in vitro maturation (IVM) and to examine their roles in the cumulus-oocyte complex

Bilateral Ptosis and Lower Eyelid Ectropion Secondary to Cutaneous Leishmaniasis

A 73-year-old white woman had a 14-month history of an extensive, disfiguring facial lesion involving the cheeks, nose, and eyelids, resulting in exposure keratopathy. A biopsy of the facial lesion established the diagnosis of cutaneous leishmania, and the lesion responded to treatment with itraconazole.Arch Ophthalmol. 1998;116:1244-1245--

Bisphenol S is present in culture media used for ART and cell culture

International audienceSTUDY QUESTION: Do plastic laboratory consumables and cell culture media used in ART contain bisphenols?SUMMARY ANSWER: The majority of human embryo culture media assessed contained bisphenol S close to the nanomolarconcentration range, while no release of bisphenols by plastic consumables was detected under routine conditions.WHAT IS KNOWN ALREADY: The deleterious effect of the endocrine disruptor bisphenol A (BPA) on female fertility raised concernsregarding ART outcome. BPA was detected neither in media nor in the majority of plastic consumables used in ART; however, it mighthave already been replaced by its structural analogs, including bisphenol S (BPS).STUDY DESIGN, SIZE, DURATION: Seventeen plastic consumables and 18 cell culture and ART media were assessed for thepresence of bisphenols.PARTICIPANTS/MATERIALS, SETTING, METHODS: Ten different bisphenols (bisphenol A, S, AF, AP, B, C, E, F, P and Z) weremeasured using an isotopic dilution according to an on-line solid phase extraction/liquid chromatography/mass spectrometry method.MAIN RESULTS AND THE ROLE OF CHANCE: While the plastic consumables did not release bisphenols under routine conditions,16 of the 18 cell culture and ART media assessed contained BPS. Six media exhibited BPS concentrations higher than 1 nM and reached upto 6.7 nM (1693 ng/l).LARGE SCALE DATA: N/A.LIMITATIONS, REASONS FOR CAUTION: Further studies are required to investigate a greater number of ART media to identifyless potentially harmful ones, in terms of bisphenol content.WIDER IMPLICATIONS OF THE FINDINGS: As BPS has already been reported to impair oocyte quality at nanomolar concentrations,its presence in ART media, at a similar concentration range, could contribute to a decrease in the ART success rate. Thus far, therehas been no regulation of these compounds in the ART context.STUDY FUNDING/COMPETING INTERESTS: This study was financially supported by the ‘Centre-Val de Loire’ Region (Bemolproject, APR IR 2017), INRAE, BRGM, the French National Research Agency (project ANR-18-CE34-0011-01 MAMBO) and theBioMedicine Agency (Project 18AMP006 FertiPhenol). The authors declare that they have no conflict of interest that could be perceived asprejudicing the impartiality of the reported research

Bisphenols are present in culture media used for ART and cell culture

International audienceStudy question Do plastic laboratory consumables and cell culture media used in human ART contain bisphenols? Summary answer Human embryo development media contained bisphenols close to the nanomolar concentration range while no release of bisphenols by plastic consumables was detected under routine conditions. What is known already The deleterious effect of the endocrine disruptor bisphenol A (BPA) on female fertility raised concerns regarding ART outcome. BPA was detected neither in media nor in the majority of plastic consumables used in ART, however it might have already been replaced by its structural analogs, including bisphenol S (BPS). Study design, size, duration Seventeen plastic consumables and 18 cell culture and ART media were assessed for the presence of bisphenols. Participants/materials, setting, methods Ten different bisphenols (bisphenol A, S, AF, AP, B, C, E, F, P, and Z) were measured using an isotopic dilution according to an on-line solid phase extraction / liquid chromatography/mass spectrometry method. Main results and the role of chance While all the plastic consumables of this study did contain bisphenols, none of them did release bisphenols under routine conditions. Moreover, 16 of the 18 cell culture and ART media assessed contained bisphenols, including 8 among the 10 media used in human ART. Five human ART media exhibited bisphenol concentrations higher than 0.8 nM and reached up to 3.2 nM (799 ng/L). Limitations, reasons for caution Further studies are required to investigate a greater number of ART media to identify less potentially harmful ones, in terms of bisphenol content. Wider implications of the findings: As BPS has already been reported to impair oocyte quality at nanomolar concentrations, its presence in ART media, at a similar concentration range, could contribute to a decrease in the ART success rate. Thus far, there has been no regulation of these compounds in the ART context. Trial registration number Not applicabl

Effet cocktail des perturbateurs endocriniens: bisphénols et cellules ovariennes de granulosa humaines

International audienceLa population humaine est fréquemment exposée à des polluants environnementaux incluant des perturbateurs endocriniens. Parmi eux, le Bisphénol A (un plastifiant notamment utilisé dans les emballages alimentaires, affecte la reproduction en altérant la prolifération et la production d’hormones sexuelles ou stéroïdogenèse (œstradiol et progestérone) des cellules ovariennes de granulosa. Ces fonctions sont essentielles à la croissance du follicule ovarien et à la maturation de l’ovocyte. Le BPA reconnu comme perturbateur endocrinien est interdit en France dans l’industrie agro alimentaire depuis 2015 ce qui a provoqué l’émergence d’analogues structuraux pour le substituer tels que le BPS, BPAF, BPF, BPAP, BPB et BPE analogues non réglementés et aux effets peu connus.L ’hypothèse de ce travail est que l'homologie structurale de ces molécules peut entraîner des effets similaires. L ’objectif de cette étude consiste donc à étudier les effets in vitro de différents bisphénols seuls et en cocktail sur les cellules de granulosa humaines (CGh). Les CGh sont collectées par ponction folliculaire réalisée chez des femmes suivant un protocole de Fécondation in vitro (cultivées en milieu McCoy complet) et traitées avec les 7 bisphénols seuls ou leur cocktail équimolaire à 10 ou 50 μM pendant 48h. Les mesures de viabilité prolifération et de sécrétion de la progestérone (P4) et de l’œstradiol (E2) ont été réalisées par dosage ELISA. Un test non paramétrique d’analyse de variance (ANOVA) par permutation suivi d’un test post-hoc de Tukey (logiciel R) a permis d’analyser ces données.Les BPAF et BPAP induisent une cytotoxicité à 50 µM. Les BPA, BPAF, BPF, BPAP, BPB et le cocktail à 50 μM diminuent la prolifération. Seuls BPAF et BPAP à 50µM induisent une inhibition significative de la sécrétion de l’E2. Les BPA, BPAF, BPAP, BPE, BPB et le cocktail à 10 µM inhibent la sécrétion de P4 et pour toutes les conditions à 50µM.En conclusion, les 7 bisphénols et leur cocktail équimolaire induisent une altération de la stéroïdogenèse et de la prolifération des CGh. Les BPAP et BPAF possèdent une cytotoxicité supérieure aux autres analogues structuraux. Enfin, le cocktail semble suggérer un effet additif des 7 bisphénols qui serait en faveur d’une réglementation à l’échelle de la famille de ces molécules plutôt qu’une règlementation individuelle

Bisphenol S alters the steroidome in the preovulatory follicle, oviduct fluid and plasma in ewes with contrasted metabolic status

International audienceBisphenol A (BPA), a plasticizer and endocrine disruptor, has been substituted by bisphenol S (BPS), a structural analogue that had already shown adverse effects on granulosa cell steroidogenesis. The objective of this study was to assess the effect of chronic exposure to BPS, a possible endocrine disruptor, on steroid hormones in the ovary, oviduct and plasma using the ewe as a model. Given the interaction between steroidogenesis and the metabolic status, the BPS effect was tested according to two diet groups. Eighty adult ewes were allotted to restricted (R) and well-fed (WF) groups, that were further subdivided into two subgroups. Ewes were exposed to 50 µg BPS/kg/day in their diet (R50 and WF50 groups) or were unexposed controls (R0 and WF0 groups). After at least 3 months of BPS exposure, preovulatory follicular fluid, oviduct fluid and plasma were collected and steroid hormones were analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). A deleterious effect of restricted diet on the volume of oviduct fluid and numbers of pre-ovulatory follicles was observed. Exposure to BPS impaired estradiol concentrations in both follicular and oviduct fluids of well-fed ewes and progesterone, estradiol and estrone concentrations in plasma of restricted ewes. In addition, a significant interaction between metabolic status and BPS exposure was observed for seven steroids, including estradiol. In conclusion, BPS acts in ewes as an endocrine disruptor with differential actions according to metabolic status