Intergenerational Influences between Maternal Polycystic Ovary Syndrome and Offspring: An Updated Overview

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder. Affecting 5%-10% 1 Li R. Zhang Q. Yang D. Li S. Lu S. Wu X. et al. Prevalence of polycystic ovary syndrome in women in China: a large community-based study. Hum Reprod. 2013; 28: 2562-2569 Crossref PubMed Scopus (188) Google Scholar of reproductive-aged women, PCOS is characterized by hyperandrogenemia, anovulation, and insulin resistance (IR), with long-term effects throughout the different stages of a woman's life. During gestation, women with PCOS have greater androgen concentrations. 2 Sir-Petermann T. Maliqueo M. Angel B. Lara H.E. Perez-Bravo F. Recabarren S.E. Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization. Hum Reprod. 2002; 17: 2573-2579 Crossref PubMed Google Scholar Intrauterine exposure to high androgen concentrations may cause fetal reprogramming or placental changes through epigenetic regulation or other mechanisms, thus causing changes in multiple systems in the offspring and ultimately affecting growth and development. The hormonal and metabolic alterations have been found in brothers of women with PCOS, 3 Sam S. Coviello A.D. Sung Y.A. Legro R.S. Dunaif A. Metabolic phenotype in the brothers of women with polycystic ovary syndrome. Diabetes Care. 2008; 31: 1237-1241 Crossref PubMed Scopus (45) Google Scholar ,4 Torchen L.C. Kumar A. Kalra B. Savjani G. Sisk R. Legro R.S. et al. Increased antimüllerian hormone levels and other reproductive endocrine changes in adult male relatives of women with polycystic ovary syndrome. Fertil Steril. 2016; 106: 50-55 Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar which may reflect the effects of PCOS susceptibility genes or programming effects of the intrauterine environment. Furthermore, a greater risk of pregnancy complications, 5 Palomba S. de Wilde M.A. Falbo A. Koster M.P. La Sala G.B. Fauser B.C. Pregnancy complications in women with polycystic ovary syndrome. Hum Reprod Update. 2015; 21: 575-592 Crossref PubMed Scopus (163) Google Scholar , 6 Damm P. Houshmand-Oeregaard A. Kelstrup L. Lauenborg J. Mathiesen E.R. Clausen T.D. Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia. 2016; 59: 1396-1399 Crossref PubMed Scopus (182) Google Scholar , 7 Walker C.K. Krakowiak P. Baker A. Hansen R.L. Ozonoff S. Hertz-Picciotto I. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatr. 2015; 169: 154-162 Crossref PubMed Scopus (136) Google Scholar the use of metformin during pregnancy, 8 Rowan J.A. Rush E.C. Plank L.D. Lu J. Obolonkin V. Coat S. et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age. BMJ Open Diabetes Res Care. 2018; 6: e000456 Crossref PubMed Google Scholar and maternal metabolic abnormalities (including obesity or IR 9 Drake A.J. Reynolds R.M. Impact of maternal obesity on offspring obesity and cardiometabolic disease risk. Reproduction. 2010; 140: 387-398 Crossref PubMed Scopus (278) Google Scholar ,10 Fusco S. Spinelli M. Cocco S. Ripoli C. Mastrodonato A. Natale F. et al. Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms. Nat Commun. 2019; 10: 4799 Crossref PubMed Scopus (0) Google Scholar ) may be implicated in the effects on offspring.