Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Ilpo Huhtaniemi¹, Outi Hovatta², Antonio La Marca³, Gabriel Livera⁴, Danielle Monniaux⁵, Luca Persani⁶, Abdelkader Heddar⁷, Katarzyna Jarzabek⁸, Triin Laisk-Podar⁹, Andres Salumets⁹, Juha S Tapanainen¹⁰, Reiner A Veitia¹¹, Jenny A Visser¹², Peter Wieacker¹³, Slawomir Wolczynski¹⁴, Micheline Misrahi¹⁵

Affiliations

¹ Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
² Karolinska Institute, Stockholm, Sweden, Nova Southeastern University, Fort Lauderdale, FL, USA.
³ Mother-Infant Department, University of Modena and Reggio Emilia, Modena 41100, Italy.
⁴ Laboratory of Development of the Gonads, Unit of Genetic Stability, Stem Cells and Radiation: UMR 967, INSERM; CEA/DRF/iRCM/SCSR; Univ. Paris Diderot, Sorbonne Paris Cité; Univ. Paris-Sud, Université Paris-Saclay, Fontenay aux Roses, F-92265, France.
⁵ UMR85 PRC, Physiology of Reproduction and Behavior, INRA, CNRS, IFCE, University of Tours, 37380 Nouzilly, France.
⁶ Department of Clinical Sciences & Community Health, University of Milan, Milan 20122, Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, Milan 20149, Italy.
⁷ Medical Faculty, Univ. Paris Sud and Paris Saclay, Bicetre Hospital 94275, Le Kremlin Bicêtre, France.
⁸ Department of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
⁹ Women's Clinic, Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, Tartu, Estonia; Competence Centre on Health Technologies, 50410, Estonia.
¹⁰ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University, Hospital, Helsinki 00029, Finland; Department of Obstetrics and Gynecology, University Hospital of Oulu, University of Oulu, Medical Research Center Oulu and PEDEGO Research Unit, P.O BOX 23, FI-90029 OYS, Oulu, Finland.
¹¹ Molecular Oncology and Ovarian Pathologies Université Paris-Diderot/Paris 7, Institut Jacques Monod, 15 Rue Hélène Brion, Paris Cedex 13, France.
¹² Dept. of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
¹³ Institute of Human Genetics, University Hospital of Münster, Vesaliusweg 12-14 D48149 Münster, Germany.
¹⁴ Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Sklodowskiej 24A, 15-276 Bialystok, Poland.
¹⁵ Medical Faculty, Univ. Paris Sud and Paris Saclay, Bicetre Hospital 94275, Le Kremlin Bicêtre, France. Electronic address: micheline.misrahi@aphp.fr.

PMID: 29706485
DOI: 10.1016/j.tem.2018.03.010

Free article

Review

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Ilpo Huhtaniemi et al. Trends Endocrinol Metab. 2018 Jun.

Free article

. 2018 Jun;29(6):400-419.

doi: 10.1016/j.tem.2018.03.010. Epub 2018 Apr 26.

Authors

Affiliations

¹ Institute of Reproductive and Developmental Biology, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
² Karolinska Institute, Stockholm, Sweden, Nova Southeastern University, Fort Lauderdale, FL, USA.
³ Mother-Infant Department, University of Modena and Reggio Emilia, Modena 41100, Italy.
⁴ Laboratory of Development of the Gonads, Unit of Genetic Stability, Stem Cells and Radiation: UMR 967, INSERM; CEA/DRF/iRCM/SCSR; Univ. Paris Diderot, Sorbonne Paris Cité; Univ. Paris-Sud, Université Paris-Saclay, Fontenay aux Roses, F-92265, France.
⁵ UMR85 PRC, Physiology of Reproduction and Behavior, INRA, CNRS, IFCE, University of Tours, 37380 Nouzilly, France.
⁶ Department of Clinical Sciences & Community Health, University of Milan, Milan 20122, Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, Milan 20149, Italy.
⁷ Medical Faculty, Univ. Paris Sud and Paris Saclay, Bicetre Hospital 94275, Le Kremlin Bicêtre, France.
⁸ Department of Biology and Pathology of Human Reproduction, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
⁹ Women's Clinic, Institute of Clinical Medicine, University of Tartu, L. Puusepa 8, Tartu, Estonia; Competence Centre on Health Technologies, 50410, Estonia.
¹⁰ Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University, Hospital, Helsinki 00029, Finland; Department of Obstetrics and Gynecology, University Hospital of Oulu, University of Oulu, Medical Research Center Oulu and PEDEGO Research Unit, P.O BOX 23, FI-90029 OYS, Oulu, Finland.
¹¹ Molecular Oncology and Ovarian Pathologies Université Paris-Diderot/Paris 7, Institut Jacques Monod, 15 Rue Hélène Brion, Paris Cedex 13, France.
¹² Dept. of Internal Medicine, Erasmus University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
¹³ Institute of Human Genetics, University Hospital of Münster, Vesaliusweg 12-14 D48149 Münster, Germany.
¹⁴ Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Sklodowskiej 24A, 15-276 Bialystok, Poland.
¹⁵ Medical Faculty, Univ. Paris Sud and Paris Saclay, Bicetre Hospital 94275, Le Kremlin Bicêtre, France. Electronic address: micheline.misrahi@aphp.fr.

PMID: 29706485
DOI: 10.1016/j.tem.2018.03.010

Abstract

Primary ovarian insufficiency (POI) affects ∼1% of women before 40 years of age. The recent leap in genetic knowledge obtained by next generation sequencing (NGS) together with animal models has further elucidated its molecular pathogenesis, identifying novel genes/pathways. Mutations of >60 genes emphasize high genetic heterogeneity. Genome-wide association studies have revealed a shared genetic background between POI and reproductive aging. NGS will provide a genetic diagnosis leading to genetic/therapeutic counseling: first, defects in meiosis or DNA repair genes may predispose to tumors; and second, specific gene defects may predict the risk of rapid loss of a persistent ovarian reserve, an important determinant in fertility preservation. Indeed, a recent innovative treatment of POI by in vitro activation of dormant follicles proved to be successful.

Keywords: exome; genetics; in vitro activation of dormant follicles; meiosis genes; ovary; primary ovarian insufficiency.

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Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

Affiliations

Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency

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Affiliations

Abstract

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Medical