Leptin and adiponectin blood levels in women with premature ovarian failure and age- and weight-matched women with normal menstrual cycles

Author(s):  
Cristina Laguna Benetti-Pinto ◽  
Natália Castro ◽  
Oswaldo da Rocha Grassiotto ◽  
Heraldo Mendes Garmes
Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1529 ◽  
Author(s):  
Damla Akogullari ◽  
Elgin Turkoz Uluer ◽  
H. Seda Vatansever

Premature Ovarian Failure; is characterized by the dysfunction or early depletion of ovarian reserves due to follicular loss in the ovary in women under age of 40. POF is the important cause of infertility and its etiology is still not clearly understood. Investigation of cell death mechanisms (CDM) that play a role in the follicular atresia (FA) triggered by excessive loss of granulosa cells (GCs) that provide metabolic support for oocyte and follicle development in the ovary will help to understand POF etiology. It was known that apoptosis and autophagy play a role in FA. Recent studies have shown that paraptosis, associated with endoplasmic reticulum stress (ERS), also exist in FA. POF model was established in C57BL/6 female mice by CTX and it was confirmed by increased follicle stimulating hormone (FSH), luteal hormone (LH) and decreased estradiol (E2) blood levels and follicle count. According to the results of the immunohistochemistry (IHC) cell death markers were significantly more expressed than control (C) and sham (S) groups in the POF model. In addition, more apoptotic cells were observed in the POF group compared to C and S in the TUNEL analysis. In consequence of this study apoptosis and autophagy as well as paraptosis play a role in the FA leading to POF, will help to develop new treatment protocols.


2006 ◽  
Vol 154 (5) ◽  
pp. 739-744 ◽  
Author(s):  
Paul Laissue ◽  
Sophie Christin-Maitre ◽  
Philippe Touraine ◽  
Frederique Kuttenn ◽  
Olli Ritvos ◽  
...  

Background and objective: Mutations in bone morphogenic protein 15 (BMP15) and growth/differentiation factor 9 (GDF9) lead to altered fertility in animal models. In the human, a heterozygous point mutation of BMP15 has been associated with premature ovarian failure (POF). Subject and methods: We have directly sequenced both genes in a cohort of 203 POF patients presenting with primary or secondary amenorrhea and high FSH levels and in a control population including 54 women with regular menstrual cycles who had at least one child. Results: We have identified several heterozygous variants. One alteration in GDF9 (S186Y) and one in BMP15 (L148P) may have pathogenic effects as both positions are conserved in vertebrate species, ranging from the chicken to mammals. These variants were absent in the control samples. We also found synonymous and neutral substitutions. Conclusions: We propose that although mutations in BMP15 and GDF9 are not a major cause of ovarian insufficiency, they may be involved in POF.


2003 ◽  
Vol 88 (11) ◽  
pp. 5307-5314 ◽  
Author(s):  
Elisabeth C. Larsen ◽  
Jørn Müller ◽  
Kjeld Schmiegelow ◽  
Catherine Rechnitzer ◽  
Anders Nyboe Andersen

Abstract Seventy percent of children with cancer survive. Radiation and chemotherapy may, however, impair ovarian function. The aim of this population-based study was to achieve a comprehensive knowledge of the degree of ovarian damage. Ovarian function was evaluated in 100 childhood cancer survivors and 21 controls of similar age. Menstrual cycle pattern was recorded, and strictly timed ovarian sonography and hormonal assessment were performed. The median age of the survivors was 5.4 yr (range, 0.1–15.3) at the time of diagnosis and 25.7 yr (18.5–44.4) at study entry. Seventeen survivors with premature ovarian failure had follicle-depleted or nondetectable ovaries, elevated FSH and LH, and immeasurable inhibin B. Thirteen survivors used oral contraception. Survivors with spontaneous menstrual cycles (n = 70) had smaller ovarian volume per ovary than controls (median, 4.8 vs. 6.8 cm3; P < 0.001) and a lower number of antral follicles per ovary (median, 7.5 vs. 11; P < 0.001). Further, they had lower inhibin B levels than controls (median, 94 vs. 111 pg/ml; P = 0.03) and higher estradiol levels (median, 0.12 vs. 0.08 pm; P = 0.04). Multiple linear regression analysis was performed to predict the total antral follicle number per ovary, and it showed a reduced number with ovarian irradiation (β = −0.40, P < 0.001), alkylating chemotherapy (β = −0.25, P = 0.01), older age at diagnosis (β = −0.25, P = 0.01), and longer time period off treatment (β = −0.19, P = 0.044). One in every six female survivors may develop premature ovarian failure. In survivors with spontaneous menstrual cycles, the results indicate a diminished ovarian reserve. Consequently, cessation of fertility may occur much earlier than anticipated. Adult survivors with spontaneous cycles should be informed hereof to plan childbearing.


2008 ◽  
Vol 31 (4) ◽  
pp. 11
Author(s):  
Manda Ghahremani ◽  
Courtney W Hannah ◽  
Maria Peneherrera ◽  
Karla L Bretherick ◽  
Margo R Fluker ◽  
...  

Background/Purpose: Premature ovarian failure (POF) affects 1% of women with a largely idiopathic and poorly understood etiology. The objective of this study was to identify specific epigenetic alterations by measuring DNA methylation of gene regulatory regions in women with POF vs. controls. Methods: Blood samples were collected from idiopathic POFpatients (Amenorrhea for at least 3 months and 2 serum FSH levels of > 40mIU/ml obtained > 1 month apart prior to age 40) and control women (CW) (healthy pregnancy after age 37 with out a pregnancy loss). Genomic DNA was extracted from EDTA anticoagulated blood and bisulfite converted for analysis using the Illumina Golden Gate Methylation Panel which measures DNA methylation at 1506 CpG sites in the promoter regions of 807 genes in 10 POF and 12 CW. Candidate genes with altered epigenetic marks between POF and CW at a nominal P-value < 0.05 were identified using a t-testcomparison within the Illumina bead studio software. Genes of interest were further analyzed for quantitative methylation at specific CpG sites using pyrosequencing in 30 POF and 30 CW. Results: Comparison of DNA methylation profiles of our initial POF and CW groups identified several genes with statistically significanthyper- or hypo- methylation in the POF group (P < 0.05), including the Androgen Receptor (AR)promoter region, which was significantly hypermethylated. To further validate these results, DNA methylation of the AR gene promoter was quantified bypryosequencing in a larger group of POF and CW. Pyrosequencing further confirmed a significantly higher DNA methylation of the AR promoter region inPOF vs. CW (P=0.007). Conclusions: This is a novel study identifying epigenetic alterations in POF. The hypermethylation of the AR gene in POF patients may cause decreased level of the AR in these women. This is especially interesting given a recent report of induced POF in AR deficient mice^1. Specific epigenetic markers, as identified by DNA methylation array profiling in blood, may serve as useful biomarkers for POF and other fertility disorders. However, it will need to be determined if these methylation changes are present prior to diagnosis, or are a consequence of menopause itself. Reference: 1.Hiroko S. et al. Premature ovarian failure in androgenreceptor deficient mice. PNAS;103:224-9


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