tsRNA-3043a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1

• Published in: Journal of molecular histology Vol. 55; no. 6; pp. 1147 - 1162
• Main Authors: Huang, Jianzhen, Zeng, Fang, Yi, Hongxia, Wan, Lixia, Xu, Qinggang
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2024; Springer Nature B.V
• Subjects: Aging; Animal models; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell culture; Cell proliferation; Developmental Biology; Follicle-stimulating hormone; Follicles; Granulosa cells; Life Sciences; Original Paper; Ovaries; Reproductive status; Senescence; Transcriptomes; tRNA; Apoptosis and senescence; Oxidative stress; tsRNA-3043a; Premature ovarian failure; FLT1
• ISSN: 1567-2379; 1567-2387; 1567-2387
• DOI: 10.1007/s10735-024-10256-8

Premature ovarian failure (POF) represents the pathological aging of the ovary. The tRNA-derived small fragments (tsRNAs) play significant roles in diseases; however, whether tsRNAs are involved in POF remains unknown. The cell and mice models of POF were established, and the tsRNAs profile in the ovarian tissues of POF mice was revealed through sequencing. The functions of tsRNA-3043a and its target gene
FLT1
in POF cells and mice were detected. POF mice were characterized by a decreased number of normal follicles, ovarian weight, SOD level, and serum contents of E2, LH, and FSH. A total of 81 tsRNAs were aberrantly expressed in the ovarian tissue of POF mice. The expression of tsRNA-3043a was up-regulated in POF mice. tsRNA-3043a mimics inhibited the proliferation and promoted apoptosis, lipid accumulation, and cellular senescence of ovarian granulosa KGN cells, as well as altered the transcriptome. tsRNA-3043a inhibitor had the opposite effect. tsRNA-3043a targets and binds to
FLT1.
Overexpression of
FLT1
protected KGN cells from pathological aging. tsRNA-3043a promotes the progression of POF by inhibiting
FLT1 in vitro
and
in vivo.
tsRNA-3043a targets FLT1 and promotes apoptosis and senescence of ovarian granulosa cells, leading to the progression of POF. This study provides a new target for pharmacological intervention in POF.