Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency

Author(s):Show less -

Miranda-Furtado, Cristiana L. ^[1] ; Luchiari, Heloise R. ^[2] ; Chielli Pedroso, Daiana C. ^[1] ; Kogure, Gislaine S. ^[1] ; Caetano, Lisandra C. ^[1] ; Santana, Barbara A. ^[3] ; Santana, Viviane P. ^[1] ; Benetti-Pinto, Cristina L. ^[4] ; Reis, Fernando M. ^[5] ; Maciel, Mariella A. ^[5] ; Ferriani, Rui A. ^[1] ; Ramos, Ester S. ^[2] ; Calado, Rodrigo T. ^[3] ; dos Reis, Rosana M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil

^[4] Univ Estadual Campinas, Sch Med Sci, Dept Gynecol & Obstet, Campinas, SP - Brazil

^[5] Univ Fed Minas Gerais, Dept Gynecol & Obstet, Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: Fertility and Sterility; v. 110, n. 3, p. 476+, AUG 2018.
• Web of Science Citations: 0

Abstract

Objective: To analyze whether telomere length, X-chromosome inactivation (XCI), and androgen receptor (AR) GAG polymorphism arc related to idiopathic premature ovarian insufficiency (POI). Design: Case-control study. Setting: University hospital. Patient(s): A total of 121 women, including 46 nonsyndromic POI and 75 controls. Intervention(s): None. Main Outcome Measure(s): Age, weight, height, body mass index (BMI), systolic and diastolic arterial pressure, E-2, androstenedione, T, and C-reactive protein were assessed. Telomere length was estimated by quantitative real-time polymerase chain reaction, XCI was measured using the Human Androgen Receptor and X-linked retinitis pigmentosa 2 (RP2) methylation assays. AR and FMRI polymorphism was assessed by quantitative fluorescent polymerase chain reaction and sequencing. Result(s): Premature ovarian insufficiency women had a higher mean age, weighed less, and exhibited lower C-reactive protein, E,, and androstenedione levels.The AR polymorphism did not differ between the groups. Four patients had premutation (55-200 CGG repeats), and none displayed a full mutation in the FMRI gene. However, patients with POI showed shorter telomere length and higher frequency of skewed XCI. Extreme skewing (>= 90%) was observed in 15% of women with POI, and shorter telomeres correlated with XCI skewing in both groups. Conclusion(s): Skewed XCI and shortened telomere length were associated with idiopathic POI, despite no alterations in the AR and FMRI genes. Additionally, there is a tendency for women with short telomeres to exhibit skewed XCI. (C) 2018 by American Society for Reproductive Medicine. (AU)

• FAPESP's process: 12/11566-2 - ANDROGEN RECEPTOR CAG POLIMORFISM AND TELOMERE LENGTH IN PREMATURE OVARIAN FAILURE
• Grantee: Rosana Maria dos Reis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/11069-9 - ANDROGEN RECEPTOR CAG POLIMORFISM AND TELOMERE LENGTH IN PREMATURE OVARIAN FAILURE
• Grantee: Cristiana Libardi Miranda Furtado
• Support Opportunities: Scholarships in Brazil - Post-Doctoral