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Follicle-stimulating hormone receptor gene polymorphism in chronic anovulatory women, with or without polycystic ovary syndrome: a cross-sectional study.

ABSTRACT: BACKGROUND: Polymorphisms at codons 307 and 680 are the most commonly encountered allelic variants of the follicle-stimulating hormone receptor (FSHR) gene. Studies in Caucasians suggest that certain FSHR variants are more common in women with polycystic ovary syndrome (PCOS) than normal women. The objective of this study was to determine the distribution of FSHR gene polymorphisms at codons 307 and 680 in Thai women with chronic anovulation, without (121 women) and with PCOS (133 women), using 132 known fertile women as controls. METHODS: DNA samples from peripheral blood lymphocytes were extracted and analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The prevalence of Threonine307Threonine (TT), Threonine307Alanine (TA), and Alanine307Alanine (AA) genotypes at codon 307 was 53.0% (95% CI?=?44.2-61.7%), 42.4% (95% CI?=?34-51.3%), and 4.5% (95% CI?=?1.9-10.1%) in controls; 52.6% (95% CI?=?43.8-61.3%), 39.8% (95% CI?=?31.6-48.7%), and 7.5% (95% CI?=?3.9-13.7%) in PCOS women; and 50.4% (95% CI?=?42.8-61.2%), 45.4% (95% CI?=?34.9-53.1%), and 4.5% (95% CI?=?1.5-9.6%) in anovulatory women without PCOS, respectively. The prevalence of Asparagine680Asparagine (NN), Asparagine680Serine (NS), and Serine680Serine (SS) genotypes at codon 680 was 54.5% (95% CI?=?45.7-63.2%), 40.9% (95% CI?=?32.5-49.8%), and 4.5% (95% CI?=?1.9-10.1%) in controls; 51.9% (95% CI?=?43.1-60.6%), 44.4% (95% CI?=?35.8-53.2%), and 3.8% (95% CI?=?1.4-9.0%) in PCOS women; and 47.9% (95% CI?=?40.4-58.8%), 47.1% (95% CI?=?36.5-54.7%), and 5.0% (95% CI?=?2-10.9%) in anovulatory women without PCOS, respectively. The prevalence of FSHR gene polymorphisms at both codons were not statistically different among the three groups. CONCLUSIONS: In Thai women, there was no association between the FSHR gene polymorphism at codons 307 and 680 and chronic anovulation.

SUBMITTER: Singhasena W

PROVIDER: S-EPMC4167524 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Follicle-stimulating hormone receptor gene polymorphism in chronic anovulatory women, with or without polycystic ovary syndrome: a cross-sectional study.

Singhasena Wanakan W Pantasri Tawiwan T Piromlertamorn Waraporn W Samchimchom Sudarat S Vutyavanich Teraporn T

Reproductive biology and endocrinology : RB&E 20140902

<h4>Background</h4>Polymorphisms at codons 307 and 680 are the most commonly encountered allelic variants of the follicle-stimulating hormone receptor (FSHR) gene. Studies in Caucasians suggest that certain FSHR variants are more common in women with polycystic ovary syndrome (PCOS) than normal women. The objective of this study was to determine the distribution of FSHR gene polymorphisms at codons 307 and 680 in Thai women with chronic anovulation, without (121 women) and with PCOS (133 women), ...[more]

PMID: 25179311

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Project description:BackgroundPolycystic ovary syndrome (PCOS) is a common disorder resulting in irregular menstruation and infertility due to improper follicular development and ovulation. PCOS pathogenesis is mediated by downregulated follicle-stimulating hormone receptor (FSHR) expression in granulosa cells (GCs); however, the underlying mechanism remains elusive. Unkeito (UKT) is a traditional Japanese medicine used to treat irregular menstruation in patients with PCOS. In this study, we aimed to confirm the effectiveness of UKT in PCOS by focusing on follicle-stimulating hormone (FSH) responsiveness.MethodsA rat model of PCOS was generated by prenatal treatment with 5α-dihydrotestosterone. Female offspring (3-week-old) rats were fed a UKT mixed diet or a normal diet daily. To compare the PCOS phenotype in rats, the estrous cycle, hormone profiles, and ovarian morphology were evaluated. To further examine the role of FSH, molecular, genetic, and immunohistological analyses were performed using ovarian tissues and primary cultured GCs from normal and PCOS model rats.ResultsUKT increased the number of antral and preovulatory follicles and restored the irregular estrous cycle in PCOS rats. The gene expression levels of FSHR and bone morphogenetic protein (BMP)-2 and BMP-6 were significantly decreased in the ovarian GCs of PCOS rats compared to those in normal rats. UKT treatment increased FSHR staining in the small antral follicles and upregulated Fshr and Bmps expression in the ovary and GCs of PCOS rats. There was no change in serum gonadotropin levels. In primary cultured GCs stimulated by FSH, UKT enhanced estradiol production, accompanied by increased intracellular cyclic adenosine monophosphate levels, and upregulated the expression of genes encoding the enzymes involved in local estradiol synthesis, namely Cyp19a1 and Hsd17b. Furthermore, UKT elevated the expression of Star and Cyp11a1, involved in progesterone production in cultured GCs in the presence of FSH.ConclusionsUKT stimulates ovarian follicle development by potentiating FSH responsiveness by upregulating BMP-2 and BMP-6 expression, resulting in the recovery of estrous cycle abnormalities in PCOS rats. Restoring the FSHR dysfunction in the small antral follicles may alleviate the PCOS phenotype.

Project description:Purpose:We aimed to compare the efficacy and safety of recombinant human follicle-stimulating hormone (follitropin alfa) and purified urinary human follicle-stimulating hormone (urofollitropin) for ovulation induction in Japanese women with anovulatory infertility;also to verify the noninferiority (in terms of ovulation rate) of follitropin alfa versus urofollitropin. Methods:In a Phase III, multicenter, single-blind, parallel-group study, we enrolled 265 Japanese women aged 20-39 years. The patients were menstruating without apparent ovulation or were amenorrheic (with a positive progestin challenge test), and had failed to conceive with anti-estrogen ovulation-induction therapy. The patients underwent a low-dose step-up regimen using follitropin alfa or urofollitropin with a starting dose of 75 IU. The primary endpoint was the proportion of patients who ovulated (mid-luteal serum progesterone ?5 ng/mL and/or confirmed clinical pregnancy). Secondary endpoints included the proportion of patients with a dominant follicle (?18 mm) and the duration of stimulation. Results:Ovulation occurred in 79.1% and 82.6% of the patients who received follitropin alfa and urofollitropin, respectively, in the full-analysis set (n = 261), and in 79.2% and 82.5% of the per-protocol set (n = 251). The predefined noninferiority criteria for the primary endpoint were achieved. No significant differences were observed in any secondary endpoint. Treatment-emergent adverse events were reported by a similar proportion of patients in each group (follitropin alfa, 53.5%; urofollitropin, 50.0%). Conclusions:No significant difference in the primary efficacy endpoint (rate of ovulation) was observed between follitropin alfa and purified urofollitropin in women with anovulatory infertility who were menstruating or had progestin-positive amenorrhea. The use of treatment holidays in this study prevents comparison of the data with previous trials that utilized consecutive daily doses.

Dataset Information

Follicle-stimulating hormone receptor gene polymorphism in chronic anovulatory women, with or without polycystic ovary syndrome: a cross-sectional study.

Publications

Follicle-stimulating hormone receptor gene polymorphism in chronic anovulatory women, with or without polycystic ovary syndrome: a cross-sectional study.

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