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Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and\/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.<\/jats:p>","DOI":"10.1530\/rep-14-0499","type":"journal-article","created":{"date-parts":[[2015,4,3]],"date-time":"2015-04-03T09:03:17Z","timestamp":1428051797000},"page":"R11-R24","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":73,"title":["Pathogenesis of polycystic ovary syndrome: multifactorial assessment from the foetal stage to menopause"],"prefix":"10.1093","volume":"150","author":[{"given":"Anderson Sanches","family":"de Melo","sequence":"first","affiliation":[{"name":"Unit of Human Reproduction and Gynecological Endocrinology Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Department of Paediatrics Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrine Vilan","family":"Dias","sequence":"additional","affiliation":[{"name":"Unit of Human Reproduction and Gynecological Endocrinology Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Department of Paediatrics Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 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Endocrinology Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Department of Paediatrics Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloisa","family":"Bettiol","sequence":"additional","affiliation":[{"name":"Unit of Human Reproduction and Gynecological Endocrinology Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Department of Paediatrics Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Antonio","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Unit of Human Reproduction and Gynecological Endocrinology Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"},{"name":"Department of Paediatrics Department of Gynecology and Obstetrics 2 Medical School of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenida Bandeirantes, 3900 \u2013 Campus Universit\u00e1rio \u2013 Monte Alegre, CEP: 14049-900, 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