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  • 1.
    Risal, Sanjiv
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pei, Yu
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Lu, Haojiang
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Manti, Maria
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Pui, Han-Pin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Zhao, Zhiyi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Department of Gynecology, Shandong Provincial Qianfoshan Hospital, Jinan, China.
    Massart, Julie
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Ohlsson, Claes
    Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Lindgren, Eva
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Crisosto, Nicolas
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Carlos Schachtebeck 299, Santiago, Chile / Endocrinology Unit, Clinica Las Condes, Santiago, Chile.
    Maliqueo, Manuel
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Echiburú, Barbara
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Ladrón de Guevara, Amanda
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Sir-Petermann, Teresa
    Endocrinology and Metabolism Laboratory, West Division, School of Medicine, University of Chile, Santiago, Chile.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden / School of Medical Sciences, Örebro University, Örebro, Sweden.
    Rosenqvist, Mina A.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Cesta, Carolyn E.
    Department of Medicine, Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
    Benrick, Anna
    Högskolan i Skövde, Institutionen för hälsa och lärande. Högskolan i Skövde, Forskningsspecialiseringen Hälsa och Lärande. Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Deng, Qiaolin
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome2019Ingår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, nr 12, s. 1894-1904Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.

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