HIF-1α Affects Sperm Autophagy and Motility

Abstract

Male infertility is frequently caused by decreased sperm motility. Sperm of low progressive motility showed abnormal energy metabolism and elevated autophagy rate, although the specific mechanisms remain elusive. Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor activated by hypoxia and plays a crucial role in regulating biological oxygen homeostasis. Negative correlation between sperm motility and HIF-1α expression and a potential association with the PI3K/Akt/mTOR signaling pathway were observed. To further explore the mechanisms by which HIF-1α impacts sperm motility, normal human sperm were treated with cobalt chloride (CoCl₂) or YC-1. Sperm autophagy rate, ATP production, levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and HIF-1α, p-AKT, p-mTOR, and LC3B were assessed. The results showed that CoCl₂ or YC-1 decreased sperm motility and increased sperm autophagy rate. The levels of intracellular ROS, HIF-1α, p-AKT, p-mTOR, and LC3B were significantly increased, while the levels of sperm ATP and MMP reduced. These findings suggested that HIF-1α might affect mitochondrial structure and energy generation, leading to increased autophagy rate and decreased motility in human sperm, with the PI3K/Akt/mTOR pathway potentially playing a role in this process by exerting an inhibitory effect on autophagy.