Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones
Introduction
Phthalates are a class of industrial chemicals that are dialkyl- or alkylarylesters of 1,2-benzenedicarboxylic acid and have been used for a variety of purposes [1]. Their industrial applications are related to the length of their ester chain. They are divided into two distinct groups, with very different applications, toxicological properties and classification. High molecular weight phthalates (e.g. di(2-ethylhexyl)phthalate (DEHP)) with alkyl chain lengths from 8 to 13 carbons are widely used as general-purpose plasticisers in polymers, primarily in polyvinyl chloride (PVC) resins [1], to make rigid PVC more flexible and useful, such as for wiring and cables. These phthalates are also used in a variety of consumer products, flooring and wall coverings, in food contact application and medical devices (bags for blood, parenteral nutrition, tubings and catheters) [2]. Low molecular weight phthalates with an alkyl chain of 2–7 carbons (e.g. diethyl phthalate (DEP), dibutyl phthalate (DBP)) are used in personal-care products, some cosmetics/fragrances, lacquers, varnishes, as solvents and as plasticisers in cellulose acetate [2], [3], [4]. As a result of their extensive use and their moderate resistance to degradation, phthalates are distributed widely in the environment [5]. Humans are exposed via multiple pathways, such as through food, water (oral), air (inhalation), and consumer products (dermal) [6]. Phthalates are rapidly metabolised to their monoesters in humans, and some of them can be further oxidised and conjugated with glucuronide before excretion in urine or feces [7], [8], [9]. Urinary phthalate metabolites have been used extensively as biomarkers of human exposure. Because phthalates are ubiquitous in daily life, the potential consequences of human exposure to phthalates have raised concerns in the general population.
Some phthalates are reproductive and developmental toxicants in laboratory animals (DBP, DEHP, diisobutyl (DIBP)) and are classified in the EU as reproductive toxicants; whereas others are not (DEP, diisononyl (DINP), diisodecyl (DIDP)) [10], [11], [12]. DEHP induced anti-androgenic action and abnormalities of the male reproductive system in prenatally exposed animals likely affecting the normal development of the testes [10], [12], [13], [14], [15]. Hypospadias and cryptorchidism, testicular injury leading to lowered sperm counts and reduced anogenital distance (AGD) as well as a decrease in testosterone biosynthesis involving damage to the Leydig cells [16], [17] have also been observed. In particular, phthalates may have endocrine-disrupting chemical properties that may affect the reproductive and developmental processes in humans. Consequently, recent studies have investigated the potential impact and toxicity of exposure to phthalates on aberrant male reproductive development [18]. Several recent epidemiological studies have addressed the male reproductive toxicity of phthalates [19], [20], [21], [22], [23], [24], [25], [26]. Most of the studies suggest that the urinary phthalate metabolites levels (at least one of the metabolites) may affect semen quality. Moreover, it has been documented that phthalate metabolites levels are associated with increased DNA damage, a lower sperm concentration and density as well as decreased motility and morphology. In addition, the urinary phthalate metabolites levels also appeared to be negatively associated with the testosterone level [27], [28], follicle-stimulating hormone FSH [19] and luteinising hormone (LH) [23].
Although several studies have explored the association between phthalate exposure and male reproductive function, none have carefully assessed semen quality parameters, sperm chromatin structure, sperm aneuploidy and level of reproductive hormones in one study. The aim of the present study is to assess the association of the urine phthalate metabolites levels with semen quality parameters (sperm concentration, motility, CASA parameters, morphology), sperm chromatin structure, sperm aneuploidy and the level of reproductive hormones (FSH, estradiol, testosterone) in adult men. According to our knowledge, this is the first such study that examines the relationship between phthalate metabolites levels and numerical chromosomal aberrations in sperm.
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Study population
The study population initially consisted of 344 men who were attending an infertility clinic for diagnostic purposes and who had normal semen concentration of 20–300 mln/ml or slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO 1999) [29], from the study entitled “Environmental factors and male infertility”, which is the part of the “Epidemiology of reproductive hazards in Poland – multicentre study in Poland” project supported by the National Center for Research and Development in
Study population
The study population consisted of 269 men who were attending an infertility clinics for diagnostic purposes. The mean age of the men participating in this study was 32 years old. Most of them had secondary or higher education, while about 23% had a vocational education (Table 1). Most of the participants were non smokers (Table 1). The duration of the couple's infertility lasted mostly from 1 to 2 years and from 2 to 3 years. Past diseases which may have had an impact on semen quality (e.g.
Discussion
The results of the study suggest that urinary phthalate metabolites are significantly associated with a decrease in sperm motility (5OH MEHP, MEHP, MINP), CASA parameters (VSL, VCL) (MBP), the level of testosterone (MEHP) and increase the DNA fragmentation in sperm (MBP). After applying the correction for multiple comparisons the associations between the urinary 5OHMEHP and MEHP level and the percentage of motile sperm cells and the MBP level and CASA parameters were observed.
Additionally,
Funding
This study was performed under the project “Epidemiology of reproductive hazards – multicenter study in Poland” supported by National Center for Research and Development in Poland, from grant no. PBZ-MEiN-/8/2//2006; contract no. K140/P01/2007/1.2.1.2 and the project “Lifestyle factors and semen quality” financed with a grant for statutory activity IMP 10.19.
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