Objectives: Ovarian reserve is defined as the capacity of the ovary to provide fertile oocytes. Diminished ovarian reserve (DOR) is a disorder in which ovaries are prone to go through early menopause. Where this loss of function occurs before the age of 40, it results in the premature ovarian failure (POF) disease. Throughout folliculogenesis, the follicle-stimulating hormone receptor (FSHR) starts a signaling cascade in the granulosa cells where its inactivation leads to the arrest of follicle maturation and therefore adversely affects ovarian reserve. The aim of this study was to investigate the association of genetic variation (polymorphisms and inactivating mutations) of FSHR with POF and DOR.
Materials and methods: This case-control study comprised 84 POF, 52 DOR and 80 fertile Iranian women. To determine the presence of the 566C>T mutation and the -29G>A polymorphism in FSHR, PCR-RFLP method was used. SSCP-sequencing was used to identify any allelic variants in exon 10. The expression of human FSHR at the transcript level was also compared between DOR and fertile controls by real time-polymerase chain reaction (PCR).
Results: The 566C>T polymorphism was normal in all the cases. All genotypes of -29G>A and 919G>A (exon 10) polymorphisms were observed. Statistically significant differences were seen in the genotypic distribution of both polymorphisms when comparing the control group with the DOR patient group. A decrease was observed in FSHR expression of DOR patients compared with the control group but was not significant.
Conclusions: We conclude that the -29G>A and 919G>A polymorphisms in FSHR may be associated with DOR. Although these polymorphisms had significant differences at the genic level, no significant variation was found at the transcript level.
Keywords: Allelic Variants; Follicle Stimulating Hormone Receptor; Premature Ovarian Failure.
Copyright© by Royan Institute. All rights reserved.
Conflict of interest statement
The authors declare no conflict of interest in this study.
Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls.Hum Reprod. 2016 Apr;31(4):897-904. doi: 10.1093/humrep/dew022. Epub 2016 Feb 23. Hum Reprod. 2016. PMID: 26905078
Single nucleotide polymorphisms in premature ovarian failure-associated genes in a Chinese Hui population.Mol Med Rep. 2015 Aug;12(2):2529-38. doi: 10.3892/mmr.2015.3762. Epub 2015 May 8. Mol Med Rep. 2015. PMID: 25954833 Free PMC article.
Association of allelic combinations of FSHR gene polymorphisms with ovarian response.Reprod Biomed Online. 2013 Oct;27(4):400-6. doi: 10.1016/j.rbmo.2013.07.007. Epub 2013 Jul 18. Reprod Biomed Online. 2013. PMID: 23953588
Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization.Fertil Steril. 2013 Mar 15;99(4):970-8.e1. doi: 10.1016/j.fertnstert.2013.01.086. Epub 2013 Feb 4. Fertil Steril. 2013. PMID: 23380184 Review.
Mutations and polymorphisms of the FSH receptor (FSHR) gene: clinical implications in female fecundity and molecular biology of FSHR protein and gene.Obstet Gynecol Surv. 2008 Dec;63(12):785-95. doi: 10.1097/OGX.0b013e31818957eb. Obstet Gynecol Surv. 2008. PMID: 19017414 Review.
Cited by 2 articles
Correlation of follicle-stimulating hormone receptor gene Asn 680 Ser (rs6166) polymorphism with female infertility.J Family Med Prim Care. 2019 Oct 31;8(10):3356-3361. doi: 10.4103/jfmpc.jfmpc_685_19. eCollection 2019 Oct. J Family Med Prim Care. 2019. PMID: 31742168 Free PMC article.
"Evaluation of four genes associated with primary ovarian insufficiency in a cohort of Mexican women".J Assist Reprod Genet. 2018 Aug;35(8):1483-1488. doi: 10.1007/s10815-018-1232-3. Epub 2018 Jun 18. J Assist Reprod Genet. 2018. PMID: 29916099 Free PMC article.
- Broekmans FJ, Knauff EA, Te Velde ER, Macklon NS, Fauser BC. Female reproductive ageing: current knowledge and future trends. Trends Endocrinol Metab. 2007;18(2):58–65. - PubMed
- Coulam CB. Premature gonadal failure. Fertil Steril. 1982;38(6):645–655. - PubMed
- Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67(4):604–606. - PubMed
- Cordts EB, Christofolini DM, Dos Santos AA, Bianco B, Barbosa CP. Genetic aspects of premature ovarian failure: a literature review. Arch Gynecol Obstet. 2011;283(3):635–643. - PubMed
- Shelling AN. Premature ovarian failure. Reproduction. 2010;140(5):633–641. - PubMed