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Citations to this article

TP63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis
Chengzi Huang, … , Zi-Jiang Chen, Shidou Zhao
Chengzi Huang, … , Zi-Jiang Chen, Shidou Zhao
Published March 1, 2023
Citation Information: J Clin Invest. 2023;133(5):e162315. https://doi.org/10.1172/JCI162315.
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Research Article Genetics Reproductive biology Article has an altmetric score of 6

TP63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis

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Abstract

The transcription factor p63 guards genome integrity in the female germline, and its mutations have been reported in patients with premature ovarian insufficiency (POI). However, the precise contribution of the TP63 gene to the pathogenesis of POI needs to be further determined. Here, in 1,030 Chinese patients with POI, we identified 6 heterozygous mutations of the TP63 gene that impaired the C-terminal transactivation-inhibitory domain (TID) of the TAp63α protein and resulted in tetramer formation and constitutive activation of the mutant proteins. The mutant proteins induced cell apoptosis by increasing the expression of apoptosis-inducing factors in vitro. We next introduced a premature stop codon and selectively deleted the TID of TAp63α in mice and observed rapid depletion of the p63+/ΔTID mouse oocytes through apoptosis after birth. Finally, to further verify the pathogenicity of the mutation p.R647C in the TID that was present in 3 patients, we generated p63+/R647C mice and also found accelerated oocyte loss, but to a lesser degree than in the p63+/ΔTID mice. Together, these findings show that TID-related variants causing constitutive activation of TAp63α lead to POI by inducing oocyte apoptosis, which will facilitate the genetic diagnosis of POI in patients and provide a potential therapeutic target for extending female fertility.

Authors

Chengzi Huang, Simin Zhao, Yajuan Yang, Ting Guo, Hanni Ke, Xin Mi, Yingying Qin, Zi-Jiang Chen, Shidou Zhao

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Total citations by year

Year: 2025 2024 2023 Total
Citations: 7 10 1 18
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2024 (10)

Title and authors Publication Year
TP63 truncating mutation causes increased cell apoptosis and premature ovarian insufficiency by enhanced transcriptional activation of CLCA2.
Fan Y, Chen S, Chu C, Yin X, Jin J, Zhang L, Yan H, Cao Z, Liu R, Xin M, Li L, Yin C
Journal of Ovarian Research 2024
Conserved genes regulating human sex differentiation, gametogenesis and fertilization
Fakhro KA, Awwad J, Garibova S, Saraiva LR, Avella M
Journal of Translational Medicine 2024
MCM8 interacts with DDX5 to promote R-loop resolution
Wen C, Cao L, Wang S, Xu W, Yu Y, Zhao S, Yang F, Chen ZJ, Zhao S, Yang Y, Qin Y
The EMBO Journal 2024
MGA loss-of-function variants cause premature ovarian insufficiency
Shuyan Tang, Ting Guo, Chengcheng Song, Lingbo Wang, Jun Zhang, Aleksandar Rajkovic, Xiaoqi Lin, Shil-Ling Chen, Yujun Liu, Weidong Tian, Bangguo Wu, Shixuan Wang, Wenwen Wang, Yunhui Lai, Ao Wang, Shuhua Xu, Li Jin, Hanni Ke, Shidou Zhao, Yan Li, Yingying Qin, Feng Zhang, Zi-Jiang Chen
Journal of Clinical Investigation 2024
Advances in the genetic etiology of female infertility.
Gu R, Wu T, Fu J, Sun YJ, Sun XX
Journal of assisted reproduction and genetics 2024
Primary ovarian insufficiency: update on clinical and genetic findings.
Federici S, Rossetti R, Moleri S, Munari EV, Frixou M, Bonomi M, Persani L
Frontiers in endocrinology 2024
N-acetylcysteine supplementation improves endocrine-metabolism profiles and ovulation induction efficacy in polycystic ovary syndrome.
Fang YQ, Ding H, Li T, Zhao XJ, Luo D, Liu Y, Li Y
Journal of ovarian research 2024
Mitochondrial Quality Control in Ovarian Function: From Mechanisms to Therapeutic Strategies.
Wang X, Liu Y, Wang J, Lu X, Guo Z, Lv S, Sun Z, Gao T, Gao F, Yuan J
Reproductive sciences (Thousand Oaks, Calif.) 2024
Identification of novel variants and candidate genes in women with 46,XX complete gonadal dysgenesis.
Ding L, Deng S, Zhang P, Zhang D, Tian Q
Reproductive biology and endocrinology : RB&E 2024
ARHGAP26 deficiency drives the oocyte aneuploidy and early embryonic development failure
Li S, Zhang Y, Yuan R, Zhu S, Bai J, Miao Y, Ou X, Wang Q, Xiong B
Cell Death and Differentiation 2024

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Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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