An estimation by the World Health Organization (WHO) has reported that 10–12 % of the world's population is infertile. A recent study claims that, 40–50 % of infertility cases is due to the male partner [1], [2]. As a result, there has been a tremendous advancement in reproductive medicine and an increased use of Assisted Reproductive Technology (ART), leading to the establishment of In Vitro Fertilization (IVF) clinics [3]. Studies on male infertility have demonstrated that the morbidity of infertility varies by demographics, with a decline in semen quality over time [4]. A recent statistical report by WHO states that male infertility is caused by both inherent and external factors, where extrinsic factors are more problematic in infertility than intrinsic ones [5]. Several reasons have been stated for the increase in infertility cases in recent years. For instance, Kasperczyk et al. (2015) claim that dietary modifications are connected to infertility issues such as hypogonadism, varicocele, and cryptorchidism [6]. Alternatively, exposure to hazardous substances, including heavy metals, in the workplace, surroundings, and lifestyle choices also contributes to decreased male fertility. Majority of in vitro and in vivo histological investigations have shown a direct correlation between the concentration of hazardous metals and concentration of hormone released, mainly testosterone, which eventually leads to a reduction in sperm production with damaged spermatogonial and spermatids [7], [8], [9], [10]. These toxic compounds are reported to replace the essential elements, leading to the loss of vital trace elements that maintain semen parameters.
As stated earlier, fertility is also hampered by a dietary imbalance that causes a deficiency in electrolytes and vital minerals [Kasperczyk et al. [6]]. Essential elements (EEs) maintain more than 300 enzymes and their functions during sperm metabolism. Calcium (Ca), Magnesium (Mg), Zinc (Zn), and Selenium (Se) are among the essential elements that are necessary for spermatogenesis and enhanced acrosome stability, motility, and capping [11]. Numerous studies and experiments have demonstrated that zinc supports the integrity of seminal proteins. Through coordination with seminal proteins, Zn also serves as an internal cofactor to maintain the integrity of sperm chromatin [8], [9], [12]. On the other hand, Ca2 + regulates intracellular pH and preserves the homeostasis of semen as it travels through the female vaginal canal [13].
Furthermore, Ca2 + activates protein kinase A, which promotes phosphorylation and ultimately results in sperm capacitation by acrosome reaction (AR) [14], [15]. These ions also support the maintenance of the sperm membrane potential (Em) through a number of intricate signalling pathways that enable the exchange of ions between sperm membranes through ion transporters [16]. Therefore, any membrane damage that may occur could be due to loss of ions or ion channels. Na+ and K+ ions are noted to preserve homeostasis for both internal and external membrane signalling [17]. These ions balance the osmotic pressure of semen and support the acrosomal process and its associated function in spermatozoa [18], [19], [20]. Therefore, a rise in intracellular Na+ concentration causes depolarization of the sperm cell membrane. Magnesium ions, similar to calcium, are essential for spermatogenesis, sperm acrosome formation, and the charge of capacitation [21], [22], [23]. Mg transforms nutrients into energy for cellular respiration to detoxify the fertility-robbing agents [24]. Intracellular Mg acts as Ca's antagonist and is essential for sperm motility. Furthermore, significant amounts of Mg secretions in the prostate gland activate Ca-dependent ATPase, which in turn supports sperm capacitation [25], [26]. Se is yet another crucial element required to maintain the physiological function and storage of sperm. It acts as a cofactor for glutathione peroxidase, an enzyme of enzymatic antioxidants that scavenge ROS [27]. Se also serves as an active principle in sustaining sperm morphology.
Seminal proteins, in particular semenogelin, protect sperm integrity and morphology over oligospermia and oligoteratospermia [28]. More than 100 Sg proteins have been identified and their role in semen biology has been documented. These trace elements interact with seminal proteins such as semenogelin to modulate sperm function. Furthermore, studies have reported a strong correlation between Zn and seminal proteins in maintaining sperm motility and morphology in normal subjects [28], [29], [30].
Taking into account the significance of these essential elements in the regulation of semen, we intended to study the influence of the trace elements on spermatozoa and semen parameters like sperm count, morphology, semen fluidity, and DNA stability between teratozoospermic and normozoospermic subjects. This is the first study to report a comprehensive investigation on the joint effects of essential elements on sperm morphology, motility, DNA integrity, and interaction with seminal proteins such as semenogelin in normozoospermic and teratozoospermic subjects. The study involves quantifying essential elements, sperm morphological analysis, sperm integrity check through DNA fragmentation index and metal binding site analysis. These results are envisaged to provide critical information that could assist in scheming alternative strategies for infertility treatment that promote natural conception.
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