Cristiana L Miranda-Furtado1, Heloise R Luchiari2, Daiana C Chielli Pedroso1, Gislaine S Kogure1, Lisandra C Caetano1, Bárbara A Santana3, Viviane P Santana1, Cristina L Benetti-Pinto4, Fernando M Reis5, Mariella A Maciel5, Rui A Ferriani1, Ester S Ramos2, Rodrigo T Calado3, Rosana M Dos Reis6. 1. Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. 2. Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. 3. Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. 4. Department of Gynecology and Obstetrics, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil. 5. Department of Gynecology and Obstetrics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 6. Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: romareis@fmrp.usp.br.
Abstract
OBJECTIVE: To analyze whether telomere length, X-chromosome inactivation (XCI), and androgen receptor (AR) GAG polymorphism are 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, E2, 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 FMR1 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, E2, 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 FMR1 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 FMR1 genes. Additionally, there is a tendency for women with short telomeres to exhibit skewed XCI.
OBJECTIVE: To analyze whether telomere length, X-chromosome inactivation (XCI), and androgen receptor (AR) GAG polymorphism are 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, E2, androstenedione, T, and C-reactive protein were assessed. Telomere length was estimated by quantitative real-time polymerase chain reaction, XCI was measured using the HumanAndrogen Receptor and X-linked retinitis pigmentosa 2 (RP2) methylation assays. AR and FMR1 polymorphism was assessed by quantitative fluorescent polymerase chain reaction and sequencing. RESULT(S): Premature ovarian insufficiencywomen had a higher mean age, weighed less, and exhibited lower C-reactive protein, E2, 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 FMR1 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 FMR1 genes. Additionally, there is a tendency for women with short telomeres to exhibit skewed XCI.
Authors: Mette W Christensen; David L Keefe; Fang Wang; Christine S Hansen; Isaac J Chamani; Carolyn Sommer; Mette Nyegaard; Palle D Rohde; Anders L Nielsen; Jonas Bybjerg-Grauholm; Ulrik S Kesmodel; Ulla B Knudsen; Kirstine Kirkegaard; Hans Jakob Ingerslev Journal: J Assist Reprod Genet Date: 2021-10-01 Impact factor: 3.412
Authors: Anne-Julie Fattet; Simon Toupance; Simon N Thornton; Nicolas Monnin; Jean-Louis Guéant; Athanase Benetos; Isabelle Koscinski Journal: J Ovarian Res Date: 2020-08-21 Impact factor: 4.234