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Cited by 85Ovarian function and disordersReproductive Biology and FertilityGenetic and Kidney Cyst Diseases

Gene Expression in Granulosa Cells From Small Antral Follicles From Women With or Without Polycystic Ovaries

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Owens, Lisa Ann, Kristensen, Stine Gry, Lerner, Avi, Christopoulos, Georgios, Lavery, Stuart, Hanyaloglu, Aylin C, Hardy, Kate, Yding Andersen, Claus +1 more·2019·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2019-00780PMC PMC6822643
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Abstract

Context: Polycystic ovary syndrome (PCOS) is the most common cause of anovulation. A key feature of PCOS is arrest of follicles at the small- to medium-sized antral stage. Objective and Design: To provide further insight into the mechanism of follicle arrest in PCOS, we profiled (i) gonadotropin receptors; (ii) characteristics of aberrant steroidogenesis; and (iii) expression of anti-Müllerian hormone (AMH) and its receptor in granulosa cells (GCs) from unstimulated, human small antral follicles (hSAFs) and from granulosa lutein cells (GLCs). Setting: GCs from hSAFs were collected at the time of cryopreservation of ovarian tissue for fertility preservation and GLCs collected during oocyte aspiration before in vitro fertilization/intracytoplasmic sperm injection. Participants: We collected hSAF GCs from 31 women (98 follicles): 10 with polycystic ovaries (PCO) and 21 without. GLCs were collected from 6 women with PCOS and 6 controls undergoing IVF. Main Outcome Measures: Expression of the following genes: LHCGR, FSHR, AR, INSR, HSD3B2, CYP11A1, CYP19, STAR, AMH, AMHR2, FST, INHBA, INHBB in GCs and GLCs were compared between women with PCO and controls. Results: GCs in hSAFs from women with PCO showed higher expression of LHCGR in a subset (20%) of follicles. Expression of FSHR (P < 0.05), AR (P < 0.05), and CYP11A1 (P < 0.05) was lower, and expression of CYP19A1 (P < 0.05), STAR (P < 0.05), HSD3B2 (P = NS), and INHBA (P < 0.05) was higher in PCO GCs. Gene expression in GL cells differed between women with and without PCOS but also differed from that in GCs. Conclusions: Follicle arrest in PCO is characterized in GCs by differential regulation of key genes involved in follicle growth and function.

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  • Granulosa cells from small antral follicles of women with PCOS prematurely switch from FSH to LH responsiveness, indicated by elevated LH receptor expression and reduced FSH receptor expression compared with unaffected women.

    “The granulosa cells from small antral follicles of women with PCOS prematurely switch from FSH to LH responsiveness, as indicated by elevated LH receptor expression and reduced FSH receptor expression compared with unaffected women (Franks & Hardy, 2020; Kanamarlapudi et al., 2016; Owens et al., 2019).”

    From Endometriosis and polycystic ovary syndrome are diametric disorders (2021) · cites this paper as Owens et al., 2019

    The Discussion reports reduced FSHR expression and increased LHCGR expression in a subpopulation of small antral follicles from women with PCO. It does not establish a general switch from FSH to LH responsiveness: the passage on functional responses says only some follicles showed premature LH responsiveness, while FSH-stimulated hormone production was augmented. (LLM, conf=0.88)

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Authors
Owens, L. A., Kristensen, S. G., Lerner, A., Christopoulos, G., Lavery, S., Hanyaloglu, A. C., Hardy, K., Yding Andersen, C., & Franks, S.
Affiliations
  • Hammersmith Hospital (GB)
  • University of Copenhagen (DK)
  • Imperial College Healthcare NHS Trust (GB)
  • Faculty of Health and Medical Sciences, Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark
Corresponding author
Owens, Lisa Ann
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2019-07-05
Volume
104
Issue
12
Pages
6182-6192
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2019-00780
PMC
PMC6822643
OpenAlex
W2955988991
Cited by
85
References
4
Citations by year
2026: 9 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 21 · 2021: 15 · 2020: 10 · 2019: 4
FWCI
11.96
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Medical Research Council (MR/M012638/1)
  • Novo Nordisk Fonden (NNF17OC0029848)
  • Imperial College London
  • Society for Endocrinology
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
polycystic ovary syndrome, polycystic ovary, granulosa cells, granulosa-lutein cells, small antral follicles, gene expression, luteinizing hormone receptor, FSH receptor, androgen receptor, insulin receptor, steroidogenesis, CYP19A1, CYP11A1, anti-Müllerian hormone, AMH receptor, inhibin
MeSH terms
Adult, Aromatase, Female, Follow-Up Studies, Gene Expression Regulation, Ovarian Follicle, Granulosa Cells, Humans, Male, Ovary, Polycystic Ovary Syndrome, Prognosis, Receptors, FSH, Receptors, LH, Biomarkers, Case-Control Studies, Gene Expression Profiling

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