ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026
A Novel Role of DELTEX2 in Maintaining Genomic Stability of Granulosa Cells During Ovarian Aging.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Genomic instability is a key driver of ovarian aging, impairing granulosa cell (GC) function and diminishing ovarian reserve. However, the regulatory mechanisms underlying GC genomic homeostasis remain poorly defined. This study investigates the novel role of DELTEX2 (DTX2) in maintaining GC genomic stability and its underlying mechanism in the DNA damage response during ovarian aging. Our data show that telomere length was significantly shortened in both ovarian tissues and isolated GCs from aged mice. Meanwhile, DTX2 was markedly downregulated in aged ovaries, while it was highly expressed in GCs. To investigate the functional role of DTX2 in GCs, we performed knockdown and overexpression experiments in the human ovarian granulosa-like tumor cell line (KGN). DTX2 knockdown compromises genomic stability in GCs, as evidenced by reduced telomerase reverse transcriptase (TERT) expression, accelerated telomere shortening, elevated micronucleus formation, and ultimately suppressed cell proliferation coupled with G2/M phase cell cycle arrest. DTX2 overexpression upregulates TERT transcription and effectively mitigates DNA damage, as evidenced by reduced γH2AX levels and fewer micronuclei, ultimately enhancing GC proliferation and suppressing apoptosis under H
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