title: Infertility and ovarian follicle reserve depletion are associated with dysregulation of the FSH and LH receptor density in human antral follicles.
abstract: The low take-home baby rate in older women in Australia (5.8%) undergoing IVF (5.8%) is linked to the depletion of the ovarian reserve of primordial follicles. Oocyte depletion causes an irreversible change to ovarian function. We found that the young patient FSH receptor and LH receptor expression profile on the granulosa cells collected from different size follicles were similar to the expression profile reported in natural cycles in women and sheep. This was reversed in the older patients with poor ovarian reserve. The strong correlation of BMPR1B and FSH receptor density in the young was not present in the older women; whereas, the LH receptor and BMPR1B correlation was weak in the young but was strongly correlated in the older women. The reduced fertilisation and pregnancy rate was associated with a lower LH receptor density and a lack of essential down-regulation of the FSH and LH receptor. The mechanism regulating FSH and LH receptor expression appears to function independently, in vivo, from the dose of FSH gonadotrophin, rather than in response to it. Restoring an optimum receptor density may improve oocyte quality and the pregnancy rate in older women.
authors.affiliation: Stem Cell and Cancer Biology Laboratory, 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; D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D004967:Estrogens / Q000097:blood; D005260:Female; D005307:Fertilization in Vitro; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007247:Infertility, Female / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism*; D065851:Ovarian Reserve; D011374:Progesterone / Q000097:blood; D011962:Receptors, FSH / Q000378:metabolism*; D011974:Receptors, LH / Q000378:metabolism*; D015203:Reproducibility of Results; D012756:Sheep; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D004967:Estrogens; D011962:Receptors, FSH; D011974:Receptors, LH; D011374:Progesterone; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Cell signalling; FSH receptor; LH receptor; Ovarian follicle; Receptor expression