Moderate Zinc Deficiency Reduces Testicular Zip6 and Zip10 Abundance and Impairs Spermatogenesis in Mice

Abstract

Male infertility accounts for ~40% of cases of failure to conceive. Testes have a strict zinc (Zn) requirement and severe Zn deficiency compromises spermatogenesis, sperm viability, and motility, compromising fertility in men. Despite the high prevalence of marginal Zn deficiency in humans, less emphasis has been placed on understanding the consequences on male reproduction. Swiss Webster mice were used to visualize Zip protein expression during spermatogenesis using immunohistochemistry. Data suggest Zip5 imports Zn into Sertoli cells and spermatocytes, augmented by Zip10 (primary spermatocytes) and Zip8 (secondary spermatocytes). Zip6, 8, and 10 expression was retained in round spermatids, although Zip8 and Zip10 expression disappears during spermatid maturation. Zip1 and Zip6 expression was detected in mature, elongated spermatids. Zip14 was detected in undifferentiated spermatogonia and Leydig cells. Mice fed diets (n = 10/group) reduced in Zn concentration [marginal-Zn diet (MZD), 10 mg Zn/kg; low-Zn diet (ZD), 7 mg Zn/kg] for 30 d had >35% lower liver Zn concentrations than mice fed the control diet (C; 30 mg Zn/kg) (P < 0.05). Plasma Zn and testosterone concentrations and the testes Zn concentration and weight were not significantly lower than in controls. Plasma Zn was greater in the ZD group than in the C and MZD groups. Mice fed ZD had a reduced number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells (~50%; P < 0.05), compromised seminiferous tubule structure, and reduced Zip10 and Zip6 abundance (>50%; P < 0.5) compared with mice fed C. Our data provide compelling evidence that reduced Zn intake may be associated with infertility in men, perhaps independent of decreased levels of circulating Zn or testosterone, which warrants further investigation in human populations.

Analysis of the relationship between the blood concentration of several metals, macro- and micronutrients and endocrine disorders associated with male aging

“…Zinc (Zn) influences the functioning of the male reproductive system, is involved in steroidogenesis, promotes the maturation of sperm and, as an inhibitor of 5-a-reductase, regulates the concentration of dihydrotestosterone formed from testosterone. Zn excess contributes to the growth of the prostate gland (Croxford et al 2011;Fahim et al 1993), while a deficiency may cause hypogonadism, decreased testosterone levels, impaired fertility and reduced sperm viability and quantity (Yamaguchi et al 2009;Prasad 2008). In men, disruption of the Zn-to-Cu ratio reduces libido and results in erectile dysfunction and prostatic hyperplasia.…”

Zinc Depletion Causes Multiple Defects in Ovarian Function during the Periovulatory Period in Mice

“…In males, zinc deficiency leads to poor semen quality, impaired sperm motility, abnormal head morphology, and reduced number of viable sperm (25)(26)(27). In females, dietary zinc deficiency causes developmental problems throughout pregnancy (28 -30).…”

A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells

“…Studies in animal models as well as clinical studies have demonstrated that hypogonadism is a prominent feature of Zn deficiency in humans and animals (37,38); however, the underlying mechanisms responsible for these endocrine effects observed in Zn deficiency remain unclear. The present study has reported a significant decrease in serum testosterone levels and Zn concentrations in the testis and Leydig cells of mice, which is in line with the findings of previous studies on a number of male mammal species (37)(38)(39)(40). In addition, ZnT7 was prinicipally expressed and colocalized with StAR in the Leydig cells of male CD-1 mice.…”

“…It is believed that ZnTs are involved in a number of physiological pathways and processes, such as insulin synthesis and secretion in the pancreas, cognitive function, bone development and body adiposity (37,45). The roles of ZnTs in the pathogenesis of disease have received great attention and monitoring cellular Zn status may have an important impact on disease prevention and treatment (45,46).…”