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4. At the crossroads of fertility and metabolism: the importance of AMPK-dependent signaling in female infertility associated with hyperandrogenism.

Author

Froment, Pascal, Plotton, Ingrid, Giulivi, Cecilia, Fabre, Stephane, Khoueiry, Rita, Mourad, Nizar I, Horman, Sandrine, Ramé, Christelle, Rouillon, Charlène, Grandhaye, Jeremy, Bigot, Yves, Chevaleyre, Claire, Le Guevel, Remy, Mallegol, Patricia, Andriantsitohaina, Ramaroson, Guerif, Fabrice, Tamburini, Jérôme, Viollet, Benoit, Foretz, Marc, and Dupont, Joelle

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Infertility, Clinical Research, Genetics, Contraception/Reproduction, Nutrition, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Metabolic and endocrine, AMP-Activated Protein Kinases, Animals, Anti-Mullerian Hormone, Biological Phenomena, Female, Fertility, Humans, Hyperandrogenism, Infertility, Female, Metformin, Mice, Polycystic Ovary Syndrome, fertility, granulosa cells, AMPK, AMP-activated protein kinases, androgens, polycystic ovary syndrome, ovary, anti-Mullerian hormone, testosterone, anti-Müllerian hormone, Medical and Health Sciences, Studies in Human Society, Obstetrics & Reproductive Medicine, Reproductive medicine
Abstract

Study questionWhat biological processes are linked to the signaling of the energy sensor 5'-AMP-activated protein kinase (AMPK) in mouse and human granulosa cells (GCs)?Summary answerThe lack of α1AMPK in GCs impacted cell cycle, adhesion, lipid metabolism and induced a hyperandrogenic response.What is known alreadyAMPK is expressed in the ovarian follicle, and its activation by pharmacological medications, such as metformin, inhibits the production of steroids. Polycystic ovary syndrome (PCOS) is responsible for infertility in approximately 5-20% of women of childbearing age and possible treatments include reducing body weight, improving lifestyle and the administration of a combination of drugs to improve insulin resistance, such as metformin.Study design, size, durationAMPK signaling was evaluated by analyzing differential gene expression in immortalized human granulosa cells (KGNs) with and without silencing α1AMPK using CRISPR/Cas9. In vivo studies included the use of a α1AMPK knock-out mouse model to evaluate the role of α1AMPK in folliculogenesis and fertility. Expression of α1AMPK was evaluated in primary human granulosa-luteal cells retrieved from women undergoing IVF with and without a lean PCOS phenotype (i.e. BMI: 18-25 kg/m2).Participants/materials, setting, methodsα1AMPK was disrupted in KGN cells and a transgenic mouse model. Cell viability, proliferation and metabolism were evaluated. Androgen production was evaluated by analyzing protein levels of relevant enzymes in the steroid pathway by western blots, and steroid levels obtained from in vitro and in vivo models by mass spectrometry. Differential gene expression in human GC was obtained by RNA sequencing. Analysis of in vivo murine folliculogenesis was performed by histology and immunochemistry, including evaluation of the anti-Müllerian hormone (AMH) marker. The α1AMPK gene expression was evaluated by quantitative RT-PCR in primary GCs obtained from women with the lean PCOS phenotype (n = 8) and without PCOS (n = 9).Main results and the role of chanceSilencing of α1AMPK in KGN increased cell proliferation (P

Published
2022

5. Metformin in Reproductive Biology

Author

Faure, Melanie, Bertoldo, Michael J, Khoueiry, Rita, Bongrani, Alice, Brion, François, Giulivi, Cecilia, Dupont, Joelle, and Froment, Pascal

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Pediatric, Contraception/Reproduction, Diabetes, Infertility, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Reproductive health and childbirth, Metabolic and endocrine, Good Health and Well Being, testis, ovary, metformin, oocytes, spermatogenesis, Clinical Sciences, Nutrition and Dietetics, Clinical sciences
Abstract

Initially produced in Europe in 1958, metformin is still one of the most widely prescribed drugs to treat type II diabetes and other comorbidities associated with insulin resistance. Metformin has been shown to improve fertility outcomes in females with insulin resistance associated with polycystic ovary syndrome (PCOS) and in obese males with reduced fertility. Metformin treatment reinstates menstrual cyclicity, decreases the incidence of cesareans, and limits the number of premature births. Notably, metformin reduces steroid levels in conditions associated with hyperandrogenism (e.g., PCOS and precocious puberty) in females and improves fertility of adult men with metabolic syndrome through increased testosterone production. While the therapeutical use of metformin is considered to be safe, in the last 10 years some epidemiological studies have described phenotypic differences after prenatal exposure to metformin. The goals of this review are to briefly summarize the current knowledge on metformin focusing on its effects on the female and male reproductive organs, safety concerns, including the potential for modulating fetal imprinting via epigenetics.

Published
2018

8. Epigenetic regulation by TET1 in gene-environmental interactions influencing susceptibility to congenital malformations

Author

van der Veer, Bernard K., primary, Chen, Lehua, additional, Tsaniras, Spyridon Champeris, additional, Brangers, Wannes, additional, Chen, Qiuying, additional, Schroiff, Mariana, additional, Custers, Colin, additional, Kwak, Harm H.M., additional, Khoueiry, Rita, additional, Cabrera, Robert, additional, Gross, Steven S., additional, Finnell, Richard H., additional, Lei, Yunping, additional, and Koh, Kian Peng, additional

Published
2024
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10. PDGFRα+ Cells in Embryonic Stem Cell Cultures Represent the In Vitro Equivalent of the Pre-implantation Primitive Endoderm Precursors

Author

Lo Nigro, Antonio, de Jaime-Soguero, Anchel, Khoueiry, Rita, Cho, Dong Seong, Ferlazzo, Giorgia Maria, Perini, Ilaria, Abon Escalona, Vanesa, Aranguren, Xabier Lopez, Chuva de Sousa Lopes, Susana M., Koh, Kian Peng, Conaldi, Pier Giulio, Hu, Wei-Shou, Zwijsen, An, Lluis, Frederic, and Verfaillie, Catherine M.

Published
2017
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11. Supplementary Figure 2 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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12. Data from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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13. Data from Cytokeratin-20 and Survivin-Expressing Circulating Tumor Cells Predict Survival in Metastatic Colorectal Cancer Patients by a Combined Immunomagnetic qRT-PCR Approach

Author

Ning, Yan, primary, Hanna, Diana L., primary, Zhang, Wu, primary, Mendez, Angela, primary, Yang, Dongyun, primary, El-Khoueiry, Rita, primary, Matsusaka, Satoshi, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, Parekh, Anish, primary, Okazaki, Satoshi, primary, Berger, Martin D., primary, Barzi, Afsaneh, primary, and Lenz, Heinz-Josef, primary

Published
2023
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14. Supplementary Figure 1 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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15. Data from Prognostic Role of Lemur Tyrosine Kinase-3 Germline Polymorphisms in Adjuvant Gastric Cancer in Japan and the United States

Author

Wakatsuki, Takeru, primary, LaBonte, Melissa J., primary, Bohanes, Pierre O., primary, Zhang, Wu, primary, Yang, Dongyun, primary, Azuma, Mizutomo, primary, Barzi, Afsaneh, primary, Ning, Yan, primary, Loupakis, Fotios, primary, Saadat, Siamak, primary, Volz, Nico, primary, Stintzing, Sebastian, primary, El-Khoueiry, Rita, primary, Koizumi, Wasaburo, primary, Watanabe, Masahiko, primary, Shah, Manish, primary, Stebbing, Justin, primary, Giamas, Georgios, primary, and Lenz, Heinz-Josef, primary

Published
2023
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16. Supplementary Table 1 from Prognostic Role of Lemur Tyrosine Kinase-3 Germline Polymorphisms in Adjuvant Gastric Cancer in Japan and the United States

Author

Wakatsuki, Takeru, primary, LaBonte, Melissa J., primary, Bohanes, Pierre O., primary, Zhang, Wu, primary, Yang, Dongyun, primary, Azuma, Mizutomo, primary, Barzi, Afsaneh, primary, Ning, Yan, primary, Loupakis, Fotios, primary, Saadat, Siamak, primary, Volz, Nico, primary, Stintzing, Sebastian, primary, El-Khoueiry, Rita, primary, Koizumi, Wasaburo, primary, Watanabe, Masahiko, primary, Shah, Manish, primary, Stebbing, Justin, primary, Giamas, Georgios, primary, and Lenz, Heinz-Josef, primary

Published
2023
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17. Supplementary Figure 3 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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18. Supplementary Figure 4 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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19. Supplementary Table 2 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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20. Supplementary Table 3 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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21. Supplementary Figure 1 from Cytokeratin-20 and Survivin-Expressing Circulating Tumor Cells Predict Survival in Metastatic Colorectal Cancer Patients by a Combined Immunomagnetic qRT-PCR Approach

Author

Ning, Yan, primary, Hanna, Diana L., primary, Zhang, Wu, primary, Mendez, Angela, primary, Yang, Dongyun, primary, El-Khoueiry, Rita, primary, Matsusaka, Satoshi, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, Parekh, Anish, primary, Okazaki, Satoshi, primary, Berger, Martin D., primary, Barzi, Afsaneh, primary, and Lenz, Heinz-Josef, primary

Published
2023
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22. Supplementary Table 2 from Prognostic Role of Lemur Tyrosine Kinase-3 Germline Polymorphisms in Adjuvant Gastric Cancer in Japan and the United States

Author

Wakatsuki, Takeru, primary, LaBonte, Melissa J., primary, Bohanes, Pierre O., primary, Zhang, Wu, primary, Yang, Dongyun, primary, Azuma, Mizutomo, primary, Barzi, Afsaneh, primary, Ning, Yan, primary, Loupakis, Fotios, primary, Saadat, Siamak, primary, Volz, Nico, primary, Stintzing, Sebastian, primary, El-Khoueiry, Rita, primary, Koizumi, Wasaburo, primary, Watanabe, Masahiko, primary, Shah, Manish, primary, Stebbing, Justin, primary, Giamas, Georgios, primary, and Lenz, Heinz-Josef, primary

Published
2023
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23. Supplementary Table 1 from Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Author

Ning, Yan, primary, Gerger, Armin, primary, Zhang, Wu, primary, Hanna, Diana L., primary, Yang, Dongyun, primary, Winder, Thomas, primary, Wakatsuki, Takeru, primary, Labonte, Melissa J., primary, Stintzing, Sebastian, primary, Volz, Nico, primary, Sunakawa, Yu, primary, Stremitzer, Stefan, primary, El-Khoueiry, Rita, primary, and Lenz, Heinz-Josef, primary

Published
2023
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24. Supplementary Table 4 from Prognostic Role of Lemur Tyrosine Kinase-3 Germline Polymorphisms in Adjuvant Gastric Cancer in Japan and the United States

Author

Wakatsuki, Takeru, primary, LaBonte, Melissa J., primary, Bohanes, Pierre O., primary, Zhang, Wu, primary, Yang, Dongyun, primary, Azuma, Mizutomo, primary, Barzi, Afsaneh, primary, Ning, Yan, primary, Loupakis, Fotios, primary, Saadat, Siamak, primary, Volz, Nico, primary, Stintzing, Sebastian, primary, El-Khoueiry, Rita, primary, Koizumi, Wasaburo, primary, Watanabe, Masahiko, primary, Shah, Manish, primary, Stebbing, Justin, primary, Giamas, Georgios, primary, and Lenz, Heinz-Josef, primary

Published
2023
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25. Supplementary Table 3 from Prognostic Role of Lemur Tyrosine Kinase-3 Germline Polymorphisms in Adjuvant Gastric Cancer in Japan and the United States

Author

Wakatsuki, Takeru, primary, LaBonte, Melissa J., primary, Bohanes, Pierre O., primary, Zhang, Wu, primary, Yang, Dongyun, primary, Azuma, Mizutomo, primary, Barzi, Afsaneh, primary, Ning, Yan, primary, Loupakis, Fotios, primary, Saadat, Siamak, primary, Volz, Nico, primary, Stintzing, Sebastian, primary, El-Khoueiry, Rita, primary, Koizumi, Wasaburo, primary, Watanabe, Masahiko, primary, Shah, Manish, primary, Stebbing, Justin, primary, Giamas, Georgios, primary, and Lenz, Heinz-Josef, primary

Published
2023
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26. Data from Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers

Author

Talukdar, Fazlur Rahman, primary, Soares Lima, Sheila C., primary, Khoueiry, Rita, primary, Laskar, Ruhina Shirin, primary, Cuenin, Cyrille, primary, Sorroche, Bruna Pereira, primary, Boisson, Anne-Claire, primary, Abedi-Ardekani, Behnoush, primary, Carreira, Christine, primary, Menya, Diana, primary, Dzamalala, Charles P., primary, Assefa, Mathewos, primary, Aseffa, Abraham, primary, Miranda-Gonçalves, Vera, primary, Jerónimo, Carmen, primary, Henrique, Rui M., primary, Shakeri, Ramin, primary, Malekzadeh, Reza, primary, Gasmelseed, Nagla, primary, Ellaithi, Mona, primary, Gangane, Nitin, primary, Middleton, Daniel R.S., primary, Le Calvez-Kelm, Florence, primary, Ghantous, Akram, primary, Roux, Maria Leon, primary, Schüz, Joachim, primary, McCormack, Valerie, primary, Parker, M. Iqbal, primary, Pinto, Luis Felipe Ribeiro, primary, and Herceg, Zdenko, primary

Published
2023
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27. Supplementary Data from Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers

Author

Talukdar, Fazlur Rahman, primary, Soares Lima, Sheila C., primary, Khoueiry, Rita, primary, Laskar, Ruhina Shirin, primary, Cuenin, Cyrille, primary, Sorroche, Bruna Pereira, primary, Boisson, Anne-Claire, primary, Abedi-Ardekani, Behnoush, primary, Carreira, Christine, primary, Menya, Diana, primary, Dzamalala, Charles P., primary, Assefa, Mathewos, primary, Aseffa, Abraham, primary, Miranda-Gonçalves, Vera, primary, Jerónimo, Carmen, primary, Henrique, Rui M., primary, Shakeri, Ramin, primary, Malekzadeh, Reza, primary, Gasmelseed, Nagla, primary, Ellaithi, Mona, primary, Gangane, Nitin, primary, Middleton, Daniel R.S., primary, Le Calvez-Kelm, Florence, primary, Ghantous, Akram, primary, Roux, Maria Leon, primary, Schüz, Joachim, primary, McCormack, Valerie, primary, Parker, M. Iqbal, primary, Pinto, Luis Felipe Ribeiro, primary, and Herceg, Zdenko, primary

Published
2023
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28. Data from Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer

Author

Gerger, Armin, primary, El-Khoueiry, Anthony, primary, Zhang, Wu, primary, Yang, Dongyun, primary, Singh, Harpreet, primary, Bohanes, Pierre, primary, Ning, Yan, primary, Winder, Thomas, primary, LaBonte, Melissa J., primary, Wilson, Peter M., primary, Benhaim, Leonor, primary, Paez, David, primary, El-Khoueiry, Rita, primary, Absenger, Gudrun, primary, and Lenz, Heinz-Josef, primary

Published
2023
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29. Figures from Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers

Author

Talukdar, Fazlur Rahman, primary, Soares Lima, Sheila C., primary, Khoueiry, Rita, primary, Laskar, Ruhina Shirin, primary, Cuenin, Cyrille, primary, Sorroche, Bruna Pereira, primary, Boisson, Anne-Claire, primary, Abedi-Ardekani, Behnoush, primary, Carreira, Christine, primary, Menya, Diana, primary, Dzamalala, Charles P., primary, Assefa, Mathewos, primary, Aseffa, Abraham, primary, Miranda-Gonçalves, Vera, primary, Jerónimo, Carmen, primary, Henrique, Rui M., primary, Shakeri, Ramin, primary, Malekzadeh, Reza, primary, Gasmelseed, Nagla, primary, Ellaithi, Mona, primary, Gangane, Nitin, primary, Middleton, Daniel R.S., primary, Le Calvez-Kelm, Florence, primary, Ghantous, Akram, primary, Roux, Maria Leon, primary, Schüz, Joachim, primary, McCormack, Valerie, primary, Parker, M. Iqbal, primary, Pinto, Luis Felipe Ribeiro, primary, and Herceg, Zdenko, primary

Published
2023
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30. Supplementary Table 1 from Pharmacogenetic Angiogenesis Profiling for First-line Bevacizumab plus Oxaliplatin-Based Chemotherapy in Patients with Metastatic Colorectal Cancer

Author

Gerger, Armin, primary, El-Khoueiry, Anthony, primary, Zhang, Wu, primary, Yang, Dongyun, primary, Singh, Harpreet, primary, Bohanes, Pierre, primary, Ning, Yan, primary, Winder, Thomas, primary, LaBonte, Melissa J., primary, Wilson, Peter M., primary, Benhaim, Leonor, primary, Paez, David, primary, El-Khoueiry, Rita, primary, Absenger, Gudrun, primary, and Lenz, Heinz-Josef, primary

Published
2023
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32. Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development

Author

Manara, Francesca, primary, Jay, Antonin, additional, Odongo, Grace, additional, Mure, Fabrice, additional, Maroui, Mohamed, additional, Diederichs, Audrey, additional, Sirand, Cecilia, additional, Cuenin, Cyrille, additional, Granai, Massimo, additional, Mundo, Lucia, additional, Hernandez-Vargas, Hector, additional, Lazzi, Stefano, additional, Khoueiry, Rita, additional, Gruffat, Henri, additional, Herceg, Zdenko, additional, and Accardi, Rosita, additional

Published
2022
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34. In utero exposure to metformin reduces the fertility of male offspring in adulthood

Author

Faure, Mélanie C., Khoueiry, Rita, Quanico, Jusal, Acloque, Hervé, Guerquin, Marie-Justine, Bertoldo, Michael J., Chevaleyre, Claire, Ramé, Christelle, Fournier, Isabelle, Salzet, Michel, Dupont, Joëlle, Froment, Pascal, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génétique Animale et Biologie Intégrative (GABI), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), U967, Laboratoire de Développement des Gonades, Institut National de la Santé et de la Recherche Médicale (INSERM), University of New South Wales [Sydney] (UNSW), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), INSERM, Université de Lille, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, and Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Adult, Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], digestive, oral, and skin physiology, nutritional and metabolic diseases, embryo, testis, Endocrinology, Fertility, pregnancy, metformin, spermatozoa, ovary, Humans, Hypoglycemic Agents, reproductive and urinary physiology, Original Research
Abstract

International audience; Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the consequences of foetal exposure to metformin on the fertility of exposed offspring remain poorly documented. In this study, we investigated the effect of in utero metformin exposure on the fertility of female and male offspring. We observed that metformin is detectable in the blood of the mother and in amniotic fluid and blood of the umbilical cord. Metformin was not measurable in any tissues of the embryo, including the gonads. The effect of metformin exposure on offspring was sex specific. The adult females that had been exposed to metformin in utero presented no clear reduction in fertility. However, the adult males that had been exposed to metformin during foetal life exhibited a 30% reduction in litter size compared with controls. The lower fertility was not due to a change in sperm production or the motility of sperm. Rather, the phenotype was due to lower sperm head quality – significantly increased spermatozoa head abnormality with greater DNA damage – and hypermethylation of the genomic DNA in the spermatozoa associated with lower expression of the ten-eleven translocation methylcytosine dioxygenase 1 (TET1) protein. In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility.

Published
2021
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36. Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation

Author

Sklias, Athena, primary, Halaburkova, Andrea, additional, Vanzan, Ludovica, additional, Jimenez, Nora Fernandez, additional, Cuenin, Cyrille, additional, Bouaoun, Liacine, additional, Cahais, Vincent, additional, Ythier, Victor, additional, Sallé, Aurélie, additional, Renard, Claire, additional, Durand, Geoffroy, additional, Le Calvez-Kelm, Florence, additional, Khoueiry, Rita, additional, Murr, Rabih, additional, and Herceg, Zdenko, additional

Published
2021
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37. Epigenetic remodelling of enhancers in response to estrogen deprivation and re-stimulation

Author

Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Sklias, Athena, Halaburkova, Andrea, Vanzan, Ludovica, Fernández Jiménez, Nora, Cuenin, Cyrille, Bouaoun, Liacine, Cahais, Vincent, Ythier, Victor, Salle, Aurelie, Renard, Claire, Durand, Geoffroy, Le Calvez Kelm, Florence, Khoueiry, Rita, Murr, Rabih, Herceg, Zdenko, Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Sklias, Athena, Halaburkova, Andrea, Vanzan, Ludovica, Fernández Jiménez, Nora, Cuenin, Cyrille, Bouaoun, Liacine, Cahais, Vincent, Ythier, Victor, Salle, Aurelie, Renard, Claire, Durand, Geoffroy, Le Calvez Kelm, Florence, Khoueiry, Rita, Murr, Rabih, and Herceg, Zdenko

Abstract

Estrogen hormones are implicated in a majority of breast cancers and estrogen receptor alpha (ER), the main nuclear factor mediating estrogen signaling, orchestrates a complex molecular circuitry that is not yet fully elucidated. Here, we investigated genome-wide DNA methylation, histone acetylation and transcription after estradiol (E2) deprivation and re-stimulation to better characterize the ability of ER to coordinate gene regulation. We found that E2 deprivation mostly resulted in DNA hypermethylation and histone deacetylation in enhancers. Transcriptome analysis revealed that E2 deprivation leads to a global down-regulation in gene expression, and more specifically of TET2 demethylase that may be involved in the DNA hypermethylation following short-term E2 deprivation. Further enrichment analysis of transcription factor (TF) binding and motif occurrence highlights the importance of ER connection mainly with two partner TF families, AP-1 and FOX. Theseinteractions takeplace in the proximity of E2 deprivation-mediated differentially methylated and histone acetylated enhancers. Finally, while most deprivation-dependent epigenetic changes were reversed following E2 re-stimulation, DNA hypermethylation and H3K27 deacetylation at certain enhancers were partially retained. Overall, these results show that inactivation of ER mediates rapid and mostly reversible epigenetic changes at enhancers, and bring new insight into early events, which may ultimately lead to endocrine resistance.

Published
2021

38. Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers

Author

Talukdar, Fazlur Rahman, primary, Soares Lima, Sheila C., additional, Khoueiry, Rita, additional, Laskar, Ruhina Shirin, additional, Cuenin, Cyrille, additional, Sorroche, Bruna Pereira, additional, Boisson, Anne-Claire, additional, Abedi-Ardekani, Behnoush, additional, Carreira, Christine, additional, Menya, Diana, additional, Dzamalala, Charles P., additional, Assefa, Mathewos, additional, Aseffa, Abraham, additional, Miranda-Gonçalves, Vera, additional, Jerónimo, Carmen, additional, Henrique, Rui M., additional, Shakeri, Ramin, additional, Malekzadeh, Reza, additional, Gasmelseed, Nagla, additional, Ellaithi, Mona, additional, Gangane, Nitin, additional, Middleton, Daniel R.S., additional, Le Calvez-Kelm, Florence, additional, Ghantous, Akram, additional, Roux, Maria Leon, additional, Schüz, Joachim, additional, McCormack, Valerie, additional, Parker, M. Iqbal, additional, Pinto, Luis Felipe Ribeiro, additional, and Herceg, Zdenko, additional

Published
2021
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41. Regulatory dynamics of Tet1 and Oct4 resolve stages of global DNA demethylation and transcriptomic changes in the final phases of reprogramming

Author

Bartoccetti, Michela, van der Veer, Ben, Luo, Xinlong, Khoueiry, Rita, SHE, Pinyi, Bajaj, Manmohan, Xu, Jiayi, Janiszewski, Adiran, Thienpont, Bernard, Pasque, Vincent, and Koh, Kian Peng

Abstract

Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) involves the reactivation of endogenous pluripotency genes and global DNA demethylation, but temporal resolution of these events using existing markers is limited. Here, we generate murine transgenic lines harboring reporters for the 5-methylcytosine dioxygenase Tet1 and for Oct4. By monitoring dual reporter fluorescence during pluripotency entry, we identify a sequential order of Tet1 and Oct4 activation by proximal and distal regulatory elements. Full Tet1 activation marks an intermediate stage that accompanies predominantly repression of somatic genes, preceding full Oct4 activation, and distinguishes two waves of global DNA demethylation that target distinct genomic features but are uncoupled from transcriptional changes. Tet1 knockout shows that TET1 contributes to both waves of demethylation and activates germline regulatory genes in reprogramming intermediates but is dispensable for Oct4 reactivation. Our dual reporter system for time-resolving pluripotency entry thus refines the molecular roadmap of iPSC maturation. ispartof: Cell Reports vol:30 issue:7 pages:2150-2169 ispartof: location:United States status: published

Published
2020

45. Temporal Dynamics of Tet1 and Oct4 Gene Activation Resolve Distinct Stages of Global DNA Demethylation and Transcriptomic Changes in the Final Phases of Induced Pluripotency

Author

Bartoccetti, Michela, primary, Luo, Xinlong, additional, Veer, Ben van der, additional, Khoueiry, Rita, additional, Janiszewski, Adrian, additional, Xu, Jiayi, additional, Verfaillie, Catherine, additional, Pasque, Vincent, additional, Thienpont, Bernard, additional, and Koh, Kian, additional

Published
2019
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46. Metformin in Reproductive Biology

Author

Faure, Melanie, primary, Bertoldo, Michael J., additional, Khoueiry, Rita, additional, Bongrani, Alice, additional, Brion, François, additional, Giulivi, Cecilia, additional, Dupont, Joelle, additional, and Froment, Pascal, additional

Published
2018
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48. The interplay of dietary mycotoxins and oncogenic viruses toward human carcinogenesis: a scoping review.

Author

Mouchtaris Michailidis, Thanos, De Saeger, Sarah, Khoueiry, Rita, Odongo, Grace A., Bader, Yasmine, Dhaenens, Maarten, Herceg, Zdenko, and De Boevre, Marthe

Subjects
*ONCOGENIC viruses, *HUMAN papillomavirus, *HUMAN carcinogenesis, *HEPATITIS B virus, *PUBLIC health, *EPSTEIN-Barr virus, *PAPILLOMAVIRUSES
Abstract

AbstractBackgroundObjectivesMethodsResultsConclusionsMycotoxins, fungal metabolites prevalent in many foods, are recognized for their role in carcinogenesis, especially when interacting with oncogenic viruses.This scoping review synthesizes current evidence on the human cancer risk associated with mycotoxin exposure and oncogenic virus infections.Searches were conducted on PubMed, Embase, and Web of Science. Studies were selected based on the PECOS framework. Data extraction involved narrative and qualitative presentation of findings, with meta-analysis where feasible. Risk of bias and outcome quality were assessed using the OHAT tool and GRADE approach.From 25 included studies, 18 focused on aflatoxins and hepatitis viruses in hepatocellular carcinoma (HCC). Four studies examined aflatoxin B1 (AFB1) and human papilloma virus (HPV) in cervical cancer, while three investigated AFB1 with Epstein-Barr virus (EBV) in lymphomagenesis. The review highlights a significant synergistic effect between AFB1 and hepatitis B and C viruses in HCC development. Significant interactions between AFB1 and HPV, as well as AFB1 and EBV, were observed, but further research is needed.The synergistic impact of mycotoxins and oncogenic viruses is a critical public health concern. Future research, especially prospective cohort studies and investigations into molecular mechanisms, is essential to address this complex issue. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Lineage-specific functions of TET1 in the postimplantation mouse embryo

Author

Khoueiry, Rita, primary, Sohni, Abhishek, additional, Thienpont, Bernard, additional, Luo, Xinlong, additional, Velde, Joris Vande, additional, Bartoccetti, Michela, additional, Boeckx, Bram, additional, Zwijsen, An, additional, Rao, Anjana, additional, Lambrechts, Diether, additional, and Koh, Kian Peng, additional

Published
2017
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