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Review
. 2014 Apr 22:5:56.
doi: 10.3389/fendo.2014.00056. eCollection 2014.

Roles of reactive oxygen species in the spermatogenesis regulation

Affiliations
Review

Roles of reactive oxygen species in the spermatogenesis regulation

Giulia Guerriero et al. Front Endocrinol (Lausanne). .

Abstract

Spermatogenesis is a complex process of male germ cells proliferation and maturation from diploid spermatogonia, through meiosis, to mature haploid spermatozoa. The process involves dynamic interactions between the developing germ cells and their supporting Sertoli cells. The gonadal tissue, with abundance of highly unsaturated fatty acids, high rates of cell division, and variety of testis enzymes results very vulnerable to the overexpression of reactive oxygen species (ROS). In order to address this risk, testis has developed a sophisticated array of antioxidant systems comprising both enzymes and free radical scavengers. This chapter sets out the major pathways of testis generation, the metabolism of ROS, and highlights the transcriptional regulation by steroid receptors of antioxidant stress enzymes and their functional implications. It also deals with of the advantages of the system biology for an antioxidant under steroid control, the major selenoprotein expressed by germ cells in the testis, the phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) having multiple functions and representing the pivotal link between selenium, sperm quality, and species preservation.

Keywords: antioxidants; healthy reproduction; reactive oxygen species; selenium; spermatogenesis.

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Figures

Figure 1
Figure 1
Reactive oxygen species generation and the mechanistic antioxidative and redox defense. The testis overexpression of ROS accelerates a response by the superoxide dismutase (SOD), glutathione peroxidase (GPx), and the glutathione-S-transferase (GST). The resulting oxidation product is recycled by glutathione reductase (GR), which transforms the oxidized glutathione (GSSG) back to reduced form of glutathione (GSH) [from Ref. (13)].
Figure 2
Figure 2
Spermatogenesis ROS endocrine gene transcriptional regulation. FSH acts through its receptors in Sertoli cells (FSHR) to regulate the spermatogenesis and LH stimulates androgen production by Leydig cells after binding to LHR. However, steroid hormones, i.e., androgen and estrogen, and other agents that bind or prevent binding to steroid hormone receptors, which are present in Sertoli cells, germ cells, and Leydig cells also regulate testicular function as several growth factors, e.g., insulin like growth factor-1 (IGF-1) and epidermal growth factor (EGF), acting via their receptors possibly modulate AR and ERalpha and beta-mediated pathways. The pathway, mediated by adenosine monophosphate (cAMP), appears to be the primary intracellular signaling pathway in all testicular cells and stimulates the cAMP-dependent protein kinase (PKA). Thus, testicular function is disrupted by interactions between ROS and lipids, proteins, DNA, and several signaling pathways, some acting locally, e.g., AR and ER-mediated pathways, and others indirectly by modulating hypothalamus–pituitary function. Hormonal activation of transcriptional gene activity results in changes in cell differentiation and function. PMC, peritubular myoid cell; CRE, cAMP responsive elements; ARE, androgen-responsive elements; ERE, estrogen-responsive elements [modified from Ref. (15)].

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