Wnt10a downregulation contributes to MEHP-induced disruption of self-renewal and differentiation balance and proliferation inhibition in GC-1 cells: Insights from multiple transcriptomic profiling

• Published in: Environmental pollution (1987) 2023-09, Vol.333, p.122091-122091, Article 122091
• Main Authors: Hong, Yifan, Zhou, Xiazhu, Li, Qi, Chen, Jing, Wei, Yuexin, Wang, Siyuan, Zheng, Xiangqin, Zhao, Jie, Yu, Chengjun, Pei, Jun, Zhang, Jie, Long, Chunlan, Shen, Lianju, Wu, Shengde, Wei, Guanghui
• Format: Article
• Language: English
• Subjects: Differentiation; Germ cells; MEHP; Self-renew; Wnt10a
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2023.122091

Di (2-ethylhexyl) phthalate (DEHP), one of phthalic acid esters, has been widely used in daily products. Its main metabolite, mono (2-ethylhexyl) phthalate (MEHP) was reported to possess higher testicular toxicity than DEHP. To explore the precise mechanism in MEHP-induced testis damage, multiple transcriptomic sequencing was employed in spermatogonia cell line GC-1 cells treated with MEHP (0, 100, and 200 μM) for 24 h. Integrative omics analysis and empirical validation revealed that Wnt signaling pathway was downregulated and wnt10a, one of hub genes, may be the key player in this process. Similar results were observed in DEHP-exposed rats. MEHP-induced disturbance of self-renewal and differentiation was dose-dependent. Moreover, self-renewal proteins were downregulated; the differentiation level was stimulated. Meanwhile, GC-1 proliferation was decreased. Stable transformation strain of wnt10a overexpression GC-1 cell line constructed from lentivirus was utilized in this study. The upregulation of Wnt10a significantly reversed the dysfunction of self-renewal and differentiation and promoted the cell proliferation. Finally, retinol, predicted to be useful in CONNECTIVITY MAP (cMAP), failed to rescue the damage caused by MEHP. Cumulatively, our findings revealed that the downregulation of Wnt10a induced the imbalance of self-renew and differentiation, and inhibition of cell proliferation in GC-1 cells after MEHP exposure. [Display omitted] •RNA-seqs showed Wnt pathway was crucial in MEHP-induced testis injury.•Wnt10a was the target of MEHP-induced germ cell damage.•Reduced Wnt10a disturbed self-renew, differentiation and proliferation in GC-1.•Retinol failed to rescue MEHP caused damage in vitro.