Circular RNAs accumulate in aging human placental tissue and in stillbirth, leading to DNA damage and cellular senescence
Stillbirth placentae show accelerated aging with shortened telomeres, premature DNA breaks, increased cellular senescence, and accumulation of candidate circular RNAs at levels consistent with older gestation tissue. These circular RNAs bind to DNA in the placenta, and circ_0000284 knockdown reduces DNA breaks and senescence in primary placental cells. Therefore, circular RNAs play a role in placental aging and are associated with stillbirth, likely via decreased RNase H1 abundance, preventing circular RNA degradation and facilitating circular RNA accumulation and subsequent circular RNA:DNA complex formation. Circular RNAs may present a viable method of stillbirth risk screening.
Authors
- Hamish S. Scott (ORCID: https://orcid.org/0000-0002-5813-631X)
- Claire Trelford Roberts (ORCID: https://orcid.org/0000-0002-9250-2192)
- Matilda R. Jackson (ORCID: https://orcid.org/0000-0001-7547-7653)
- Christopher Barnett (ORCID: https://orcid.org/0000-0003-1717-3824)
- Dylan McCullough (ORCID: https://orcid.org/0000-0002-4510-3797)
- Tanja Jankovic‐Karasoulos (ORCID: https://orcid.org/0000-0003-4293-359X)
- Gustaaf Dekker (ORCID: https://orcid.org/0000-0002-7362-6683)
- Anya Lara Arthurs (ORCID: https://orcid.org/0000-0002-4382-0610)
- Melanie D. Smith (ORCID: https://orcid.org/0000-0001-7016-8245)
- Stuart T. Webb
Institutions
- South Australia Pathology (AU)
- Flinders University (AU)
- University of South Australia (AU)
- Women's and Children's Hospital (AU)
- Lyell McEwin Hospital (AU)
- Women's and Children's Health Network (AU)
- Centre for Cancer Biology (AU)
Publication Details
- Journal
- American Journal of Obstetrics and Gynecology
- Published
- 2025-08-29
- DOI
- https://doi.org/10.1016/j.ajog.2025.08.030
- Citations
- 2
- Primary Topic
- Circular RNAs in diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Channel 7 Children's Research Foundation
- Flinders University
- Flinders Foundation
- National Health and Medical Research Council