Abstract
In human spermatozoa, calcium dynamics control most of fertilization events. Progesterone, present in the female reproductive system, can trigger several types of calcium responses, such as low-frequency oscillations. Here we aimed to identify the mechanisms of progesterone-induced calcium signaling in human spermatozoa. Progesterone-induced activation of fluorophore-loaded spermatozoa was studied by fluorescent microscopy. Two computational models were developed to describe the spermatozoa calcium responses: a homogeneous one based on a system of ordinary differential equations and a three-dimensional one with added space dimensions and diffusion for the cytosolic species. In response to progesterone, three types of calcium responses were observed in human spermatozoa: a single transient rise of calcium concentration in cytosol, a steady elevation, or low-frequency oscillations. The homogenous model provided qualitative description of the oscillatory and the single spike responses, while the three-dimensional model captured the calcium peak shape and the frequency of calcium oscillations. The model analysis demonstrated that an increase in the calcium diffusion coefficient resulted in the disappearance of the calcium oscillations. Additionally, in silico analysis suggested that the spatial distribution of calcium signaling enzymes governs the appearance of calcium oscillations in progesterone-activated human spermatozoa.
Highlights
A spermatozoon is a male reproductive cell
Several types of calcium responses were observed in progesterone-treated human spermatozoa: a single transient calcium increase with the mean width of 160 s and standard deviation of 44 s and mean magnitude of 0.5 μM with standard deviation of 0.2 μM
The transient response had a secondary lower calcium increase starting at 100 ± 20 s (Figure 2c) after progesterone stimulation, and the following calcium concentration was slightly elevated in comparison to non-activated cells (Figure 2b,c)
Summary
Successful fertilization requires triggering of several events in spermatozoa. These include the acrosome reaction, an exocytotic event that results in eversion of the acrosomal vesicle [1], and the hyperactivation, a type of sperm motility characterized by an asymmetrical beating pattern of the sperm tail [2,3]. A cell can increase its cytosolic Ca2+ concentration hundreds of times in milliseconds [5]. Calcium signaling appears to be in the center of sperm activation [6,7,8,9]. Sperm cytosolic calcium rise was demonstrated in response to zona pellucida recombinant glycoproteins [11], progesterone [10,12], and other types of stimulations [9]
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