ArticleMolecular human reproduction2014
Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH.
Article in Molecular human reproduction, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- An in silico model using prognostic genetic factors for ovarian response in controlled ovarian stimulation: A systematic review.Journal of assisted reproduction and genetics · 2021Pooled it
- Exploring genotype-phenotype correlation of FSHR polymorphisms in polycystic ovary syndrome.BMC endocrine disorders · 2025Article
- Vitrification alters growth differentiation factor 9 and follicle-stimulating hormone receptor expression in human cumulus-mural granulosa cells.Clinical and experimental reproductive medicine · 2024Article
- Multiomics Analyses Provide New Insight into Genetic Variation of Reproductive Adaptability in Tibetan Sheep.Molecular biology and evolution · 2024Article
- The Ala307Thr polymorphism of the follicle-stimulating hormone receptor (FSHR) gene is associated with the dose of recombinant FSH received during IVF/ICSI treatment.JBRA assisted reproduction · 2023Article
- Endogenous, tissue-resident stem/progenitor cells in gonads and bone marrow express FSHR and respond to FSH via FSHR-3.Journal of ovarian research · 2021Review
- An overview of FSH-FSHR biology and explaining the existing conundrums.Journal of ovarian research · 2021Review
- Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence.International journal of molecular sciences · 2021Article
- Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts.BMC genomics · 2021Article
- Recent advances in understanding gonadotropin signaling.Faculty reviews · 2021Review
- Extragonadal FSHR Expression and Function-Is It Real?Frontiers in endocrinology · 2019Review
- The role of combining medroxyprogesterone 17-acetate with human menopausal gonadotropin in mouse ovarian follicular development.Scientific reports · 2018Article
- Alternative splicing: the pledge, the turn, and the prestige : The key role of alternative splicing in human biological systems.Human genetics · 2017Review
- Dynamics of the ovarian reserve and impact of genetic and epidemiological factors on age of menopause.Biology of reproduction · 2015Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Genes critical for fertility are highly conserved in mammals. Interspecies DNA sequence variation, resulting in amino acid substitutions and post-transcriptional modifications, including alternative splicing, are a result of evolution and speciation. The mammalian follicle-stimulating hormone receptor (FSHR) gene encodes distinct species-specific forms by alternative splicing. Skipping of exon 2 of the human FSHR was reported in women of North American origin and correlated with low response to ovarian stimulation with exogenous follicle-stimulating hormone (FSH). To determine whether this variant correlated with low response in women of different genetic backgrounds, we performed a blinded retrospective observational study in a Turkish cohort. Ovarian response was determined as low, intermediate or high according to retrieved oocyte numbers after classifying patients in four age groups (<35, 35-37, 38-40, >40). Cumulus cells collected from 96 women undergoing IVF/ICSI following controlled ovarian hyperstimulation revealed four alternatively spliced FSHR products in seven patients (8%): exon 2 deletion in four patients; exon 3 and exons 2 + 3 deletion in one patient each, and a retention of an intron 1 fragment in one patient. In all others (92%) splicing was intact. Alternative skipping of exons 2, 3 or 2 + 3 were exclusive to low responders and was independent of the use of agonist or antagonist. Interestingly, skipping of exon 3 occurs naturally in the ovaries of domestic cats--a good comparative model for human fertility. We tested the signaling potential of human and cat variants after transfection in HEK293 cells and FSH stimulation. None of the splicing variants initiated cAMP signaling despite high FSH doses, unlike full-length proteins. These data substantiate the occurrence of FSHR exon skipping in a subgroup of low responders and suggest that species-specific regulation of FSHR splicing plays diverse roles in mammalian ovarian function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.