title: Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility.
abstract: Reproductive ageing is linked to the depletion of ovarian primordial follicles, which causes an irreversible change to ovarian cellular function and the capacity to reproduce. The current study aimed to profile the expression of bone morphogenetic protein receptor, (BMPR1B) in 53 IVF patients exhibiting different degrees of primordial follicle depletion. The granulosa cell receptor density was measured in 403 follicles via flow cytometry. A decline in BMPR1B density occurred at the time of dominant follicle selection and during the terminal stage of folliculogenesis in the 23-30 y good ovarian reserve patients. The 40+ y poor ovarian reserve patients experienced a reversal of this pattern. The results demonstrate an association between age-induced depletion of the ovarian reserve and BMPR1B receptor density at the two critical time points of dominant follicle selection and pre-ovulatory follicle maturation. Dysregulation of BMP receptor signalling may inhibit the normal steroidogenic differentiation required for maturation in older patients.
authors.affiliation: Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia. Electronic address: sheenaregan@aapt.net.au.
authors.forename: Sheena L P
authors.initials: SL
authors.lastname: Regan
authors.affiliation: School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights, Reading RG6 6UB, UK.
authors.forename: Phil G
authors.initials: PG
authors.lastname: Knight
authors.affiliation: PIVET Medical Centre, Perth, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Yovich
authors.affiliation: PIVET Medical Centre, Perth, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Stanger
authors.affiliation: Western Australian Gynaecologic Cancer Service, King Edward Memorial Hospital for Women, Perth, Australia.
authors.forename: Yee
authors.initials: Y
authors.lastname: Leung
authors.affiliation: Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.affiliation: Stem Cell and Cancer Biology Laboratory, School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
authors.forename: Arun
authors.initials: A
authors.lastname: Dharmarajan
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia.
authors.forename: Ghanim
authors.initials: G
authors.lastname: Almahbobi
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000378:metabolism*; D006080:Ovarian Follicle / Q000378:metabolism*; D065851:Ovarian Reserve; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Bone morphogenetic protein receptor 1B; Human granulosa cells; Ovary; Receptors