PDCD4 deficiency improved 4-vinylcyclohexene dioxide-induced mouse premature ovarian insufficiency

• Published in: Reproductive biomedicine online Vol. 48; no. 4; p. 103685
• Main Authors: Zhang, Jie, Qin, Mengzhen, Kao, Chunyu, Shi, Ying, Yang, Zhi, Chen, Tao, Liu, Minghao, Fang, Liang, Gao, Fei, Qin, Yingying, Ding, Lingling
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-04-2024
• Subjects: Animals; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; bcl-2-Associated X Protein - metabolism; Cyclohexenes; Disease Models, Animal; Female; Humans; Mice; Phosphatidylinositol 3-Kinases - metabolism; POI, PDCD4; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - genetics; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; RNA-Binding Proteins - genetics; VCD; VCD; POI, PDCD4; Apoptosis
• ISSN: 1472-6483; 1472-6491; 1472-6491
• DOI: 10.1016/j.rbmo.2023.103685

What role does programmed cell death 4 (PDCD4) play in premature ovarian insufficiency (POI)?
A PDCD4 gene knockout (PDCD4–/–) mouse model was constructed, a POI mouse model was established similar to human POI with 4-vinylcyclohexene dioxide (VCD), a PDCD4-overexpressed adenovirus was designed and the regulatory role in POI in vitro and in vivo was investigated.
PDCD4 expression was significantly increased in the ovarian granulosa cells of patients with POI (P ≤ 0.002 protein and mRNA) and mice with VCD-induced POI (P < 0.001 protein expression in both mouse ovaries and granulosa cells). In POI-induced mice model, PDCD4 knockouts significantly increased anti-Müllerian hormone, oestrodiol and numbers of developing follicles, and the PI3K-AKT-Bcl2/Bax signalling pathway is involved in it.
The expression and regulation of PDCD4 significantly affects the POI pathology in a mouse model. This effect is closely related to the regulation of Bcl2/Bax and the activation of the PI3K-AKT signalling pathway.