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.