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Vertebrate reproductive science and technology
RESEARCH ARTICLE

Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line

E. R. Frost https://orcid.org/0000-0001-8696-2136 A B C F , E. A. Ford A B , A. E. Peters A B , N. L. Reed A , E. A. McLaughlin A D E , M. A. Baker A B , R. Lovell-Badge C and J. M. Sutherland A B
+ Author Affiliations
- Author Affiliations

A Priority Research Centre for Reproductive Science, Schools of Biomedical Science and Pharmacy and Environmental and Life Sciences, University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.

B Hunter Medical Research Institute, Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia.

C Stem Cell Biology and Developmental Genetics Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

D School of Science, Western Sydney University, Penrith, NSW 2751, Australia.

E School of Biological Sciences, Faculty of Science, University of Auckland, Auckland 1142, New Zealand.

F Corresponding author. Email: emily.r.frost@uon.edu.au

Reproduction, Fertility and Development 32(12) 1027-1039 https://doi.org/10.1071/RD20098
Submitted: 9 April 2020  Accepted: 29 June 2020   Published: 24 July 2020

Abstract

Ovarian granulosa cells are fundamental for oocyte maintenance and maturation. Recent studies have demonstrated the importance of members of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the granulosa cell population of mouse and horse ovaries, with perturbation of JAK1 signalling in the mouse shown to impair oocyte maintenance and accelerate primordial follicle activation. The presence and role of the JAK/STAT pathway in human granulosa cells has yet to be elucidated. In this study, expression of JAK1, STAT1 and STAT3 was detected in oocytes and granulosa cells of human ovarian sections from fetal (40 weeks gestation) and premenopausal ovaries (34–41 years of age; n = 3). To determine the effects of JAK1 signalling in granulosa cells, the human granulosa-like cell line COV434 was used, with JAK1 inhibition using ruxolitinib. Chemical inhibition of JAK1 in COV434 cells with 100 nM ruxolitinib for 72 h resulted in significant increases in STAT3 mRNA (P = 0.034) and p-Y701-STAT1 protein (P = 0.0117), demonstrating a role for JAK1 in modulating STAT in granulosa cells. This study implicates a conserved role for JAK/STAT signalling in human ovary development, warranting further investigation of this pathway in human granulosa cell function.

Graphical Abstract Image

Additional keywords: folliculogenesis, oocyte, primordial follicle, ruxolitinib.


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