AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure

Autor: Kai Xia, Fulin Wang, Xingqiang Lai, Lin Dong, Peng Luo, Suyuan Zhang, Cuifeng Yang, Hong Chen, Yuanchen Ma, Weijun Huang, Wangsheng Ou, Yuyan Li, Xin Feng, Bin Yang, Congyuan Liu, Zhenmin Lei, Xiang’an Tu, Qiong Ke, Frank Fuxiang Mao, Chunhua Deng, Andy Peng Xiang
Rok vydání: 2022
Předmět:
Zdroj: Cell reports. Medicine. 3(11)
ISSN: 2666-3791
Popis: Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we use a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screen several adeno-associated virus (AAV) serotypes and identify AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observe considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr
Databáze: OpenAIRE