Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils

Highlights

• Al-exposure caused male prostate hyperplasia, signs of cell aging and decreased in antioxidant protection.

• Al caused greater tissue damage and cellular toxicity to the female prostate, although it did not alter CAT and SOD activity.

• Al impairs the seminiferous tubules structure and decreases CAT activity in the testes.

• Al decreases folliculogenesis and reduces SOD activity in ovaries.

• Continuous exposure to Al can impair fertility of male and female adult gerbils.

Abstract

Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.

Introduction

A variety of heavy metals, such as cadmium, zinc, lead, copper and iron, among others, have been studied for their contribution to the development of various diseases in different systems, including the reproductive system (Karimi et al., 2012; Neslund-Dudas et al., 2014; Kim et al., 2015; Rzymski et al., 2015; Vella et al., 2017). The action mechanism of these metals is diverse, such as increased oxidative stress, induction of DNA damage, modification of steroidogenic pathways, endocrine disruption, and interference with cell proliferation and apoptosis pathways (Henson and Chedrese, 2004; Flora, 2011; Kim and Seo, 2012; Kim et al., 2015; Vella et al., 2017).

In addition to these metals, the effects of aluminum (Al) have also been widely investigated in different organs and systems (Moselhy et al., 2012; Wu et al., 2012; Shaw and Tomljenovic, 2013; Zhu et al., 2014). However, few studies have been conducted describing the effects of Al on the reproductive system, especially on the prostate. Al is the most abundant metal on earth and the third most common chemical element on the planet, comprising approximately 8% of the earth's crust (Priest, 2004; Kumar et al., 2009; Abdel-Moneim, 2012).

Al is widely employed in industry, construction, electronics manufacturing, food packaging, kitchen utensils, soft drink cans, as well as pharmaceutical and personal care products (Guo et al., 2005; Krewski et al., 2007; Stahl et al., 2017). Since Al is found in almost every environment, exposure to this metal is virtually unavoidable (Zatta et al., 2003; Kumar et al., 2009; Wu et al., 2012). Living beings are subject to different forms of exposure, such as inhalation; through nanoparticles that enter the body and are incorporated into various tissues and organs; orally through water and food; and parenterally via nutritional preparations, medications, and dialysis solutions (Krewski et al., 2007; Mouro et al., 2018).

Although the mechanisms of Al absorption are not yet clearly described, it is known that the absorption process depends on its chemical form, the amount present inside the intestine, the presence of competing (iron, calcium) or complexing substances (citrate), and of the intestinal intraluminal pH (van der Voet, 1992). Also, insoluble or soluble Al complexes can be produced in the digestive system, which may favor its precipitation and elimination by the gastrointestinal tract or its absorption and accumulation in tissues, respectively (Zatta et al., 2003; Erazi et al., 2010).

According to The Joint FAO/WHO Expert Committee on Food Additives (JECFA) the tolerable intake for Al was determined and corresponds to 2 mg/kg/week (Crisponi et al., 2013). However, it is known that humans can exceed maximum intake values as they are exposed to multiple sources of contamination (Yokel and McNamara, 2001; Peto, 2010; Yang et al., 2014). Al intake monitoring in human diets showed variation from 1 to more than 20 mg/day. However, these estimates do not always consider additional contamination or specific products with unusually high Al loads (Exley, 2013).

Al belongs to the group of heavy metals referred to as metalloestrogens for their ability to exert estrogenic activity when in contact with the body (Darbre, 2006; Wallace, 2015). Several studies have shown that daily exposure to hormonally active organic compounds causes permanent morphophysiological changes in the prostate (Prins et al., 2008; Lima et al., 2015; Costa et al., 2017; Campos et al., 2018; Ribeiro et al., 2018), an important accessory gland that integrates the male and female mammalian reproductive systems (Skene, 1880; Moalem and Reidenberg, 2009; Taboga et al., 2009; Seisen et al., 2012). Considering that Al exposure is unavoidable and that this element may interfere with hormonal regulation of reproductive organs, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils.