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.
Highlights
In recent years, the growing number of male infertility aroused broad attention
The purpose of this study is to determine Nuclear respiratory factor 1 (NRF1) is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1
Decline of NRF1 expression downregulated the level of steroidogenic acute regulatory protein (StAR), which resulted in a reduction in testosterone synthesis
Summary
The growing number of male infertility aroused broad attention. Kamali et al reported that out of 2492 infertile cases from 1993 to 2001, nearly 50.5% were related to male infertility, with only 11.6% were related to couple infertility [1]. It can be concluded that male fertility disorders play a key role in half of all infertility cases. Until now the mechanism of hypoxia induced infertility was still unclear. One study performed by Madrid et al in 2013 showed that high-altitude hypoxia induced plasmatic and testicular testosterone decreases since the 5th day [5]. Testosterone plays an important role in the male reproductive system, by promoting sperm maturation and maintaining male secondary sex characteristics. Studies have indicated that androgen deficiency led to male sexual dysfunction, erectile dysfunction, decreased reproductive capacity, and cardiovascular disease [6], diabetes [7], osteoporosis and other diseases [8]. Hypoxia-induced testosterone decrease might be one reason of male infertility
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