Related Experiment Video
Updated: Mar 8, 2026
Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice
Published on: July 11, 2025
Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression
Xueting Wang1, Longlu Pan2, Zhiran Zou1
1Department of Biochemistry, Institute for Nautical Medicine, Nantong University, China.
Abstract:
Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1. We designed both in vivo and in vitro experiments. Under hypoxia, the expressions of NRF1 in Leydig cells and testosterone level were significantly decreased both in vivo and in vitro. Overexpression and interference NRF1 could induced StAR and testosterone increased and decreased respectively. ChIP results confirmed the binding of NRF1 to StAR promoter region. In conclusion, decline of NRF1 expression downregulated the level of StAR, which ultimately resulted in a reduction in testosterone synthesis.
Insights
Hypoxia reduces male fertility by decreasing NRF1 (Nuclear Respiratory Factor 1) expression. This decline lowers steroidogenic acute regulatory protein (StAR) and subsequently reduces testosterone synthesis.
Area of Science:
- Reproductive Biology
- Endocrinology
- Molecular Biology
Background:
- Male infertility affects numerous couples, with hormonal imbalances playing a significant role.
- Hypoxia (low oxygen) is implicated in reproductive system dysfunction and reduced testosterone levels.
- Nuclear Respiratory Factor 1 (NRF1) expression is notably decreased under hypoxic conditions.
Purpose of the Study:
- To investigate the role of NRF1 in testosterone synthesis.
- To determine if hypoxia-induced reduction in testosterone is mediated by decreased NRF1 expression.
Main Methods:
- In vivo and in vitro experiments were conducted.
- NRF1 expression and testosterone levels were measured under normoxic and hypoxic conditions.
- Chromatin immunoprecipitation (ChIP) assays confirmed NRF1 binding to the StAR promoter.
Main Results:
- Hypoxia significantly decreased NRF1 expression and testosterone levels in Leydig cells.
- NRF1 overexpression increased StAR and testosterone levels; NRF1 interference decreased them.
- ChIP assays validated NRF1's direct binding to the steroidogenic acute regulatory protein (StAR) promoter region.
Conclusions:
- NRF1 plays a crucial role in regulating testicular steroidogenesis.
- Reduced NRF1 expression under hypoxia leads to downregulated StAR, causing a decrease in testosterone synthesis.
- NRF1 is a key molecular link between hypoxia and male hypogonadism.
