Effects of gestational and lactational exposure to low doses of PCBs 126 and 153 on anterior pituitary and gonadal hormones and on puberty in female goats

Abstract

The aim of the present study was to investigate if environmental doses of PCB 153 and PCB 126 could produce effects in a controlled animal model. Possible adverse effects on the hypothalamic–pitutitary–gonadal axis were examined by measuring gonadotrophins and gonadal steroid hormone concentrations in goat kids exposed during gestation and lactation. The concentrations of PCB 153 and PCB 126 in adipose tissue in the goat kids 9 months post-partum were 5800 ng/g (fat-weight, range; 2900–12700 ng/g) and 0.49 ng/g (fat-weight, range; 0.28–0.80 ng/g), respectively. The pre- and post-pubertal plasma concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (Prl) and progesterone (P4) were analysed. LH, FSH, Prl, and P4 were also measured during an induced oestrus cycle. The prepubertal LH concentration was significantly lower, the puberty was delayed and the P4 level during the luteal phase of an estrous cycle was higher in the group exposed to PCB 153. No significant effect of PCB 153 exposure was found on Prl and FSH. PCB 126 did not produce any effects at the exposure level tested in this study. In conclusion, perinatal exposure to PCB 153 affected the reproductive function and the puberty maturation in goats.

Introduction

Polychlorinated biphenyls (PCBs) are a group of persistent environmental chemicals that were manufactured for industrial use for about 50 years. Their resistance to degradation and strong affinity to adipose tissue allows them to accumulate in the lipid tissue of living organisms and biomagnify as they move through food chains. Although the production and use were banned 25 years ago, PCBs can still be identified in almost every component of the global ecosystem including air, water and soil, as well as in fish, animal and human tissues [1], [2].

The PCB molecule consists of a biphenyl backbone on which chlorines are added in various numbers and at different positions that gives 209 possible congeners [3]. The different PCB congeners exhibit different physicochemical properties and biological activities, which influence their accumulation, uptake, and metabolism in the environment and in organisms, leading to marked differences in congener composition between the commercial mixtures and biological extracts [4].

The toxic responses of coplanar non-ortho and mono-ortho-substituted PCB congeners resemble those observed with 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD), and the mechanistic pathway for dioxins and dioxin like PCBs are proposed to be mediated via the aryl hydrocarbon receptor (AhR) present in target tissues [5]. Depending on the binding affinity to the AhR the different congeners have been given individual toxic equivalency factors (TEFs) [5]. By calculating the amount of the different congeners with their different TEFs the potential toxicity of a mixture can be estimated. The TEF approach has been developed for risk assessment and regulatory control of exposure to complex PCDD, PCDF and PCB mixtures. On the other hand, the di-ortho-substituted PCB congeners have little or no affinity to the AhR, and the mechanisms behind toxicity are virtually unknown and they are not considered when toxicity of PCB mixtures is estimated [6].

PCBs have been shown to interfere with endocrine and reproductive functions in animals and humans [3], [5], [7], [8]. Some of the effects may be explained by the fact that several PCBs exhibit estrogenic and antiestrogenic actions [9], [10], [11], [12], [13]. Observed changes in hormone levels and reproductive function following PCB exposure has been shown in cell cultures [14] laboratory animals [9], [15], [16], wild animals [17], [18] and humans [8], [19]. PCBs stored in the adipose tissue of the mothers pass to the developing fetus and the newborn progeny via placental transfer and mother’s milk [20]. The question is whether background exposure can induce irreversible effects when animals and humans are exposed to PCB during critical windows of sexual differentiation or development [21], [22]. During the differentiation of the endocrine/reproductive systems, hormones, growth factors and other endogenous substances regulate gene expression and direct differentiation [23]. One marked difference between exposure to endocrine disruptors during critical windows in development versus during adulthood is the irreversibility of an effect during development [24], [25], [26], [27].

In order to assess possible endocrine disrupting effects following in utero PCB exposure, experiments with animals exposed to environmental relevant doses during gestation and lactation are needed. Most of the animal studies, which have investigated effects of PCBs, have been carried out with commercial mixtures [5], [28]. The complexity of such mixtures, make it difficult to interpret the toxicity of single congeners. In order to detect such effects, studies with individual PCB congeners at relevant physiological levels are required.

The co-planar PCB 126 (3,3′,4,4′,5-pentachlorobiphenyl) has high acute toxicity, relatively strong affinity to the aryl hydrocarbon receptor (AhR) and has antiestrogenic properties [29]. The di-ortho-substituted PCB 153 (2,2′,4,4′,5,5′-hexachlorobiphenyl) has low affinity to the AhR, low acute toxicity, shows estrogenic properties [7], [9] and is the most highly concentrated PCB congener found in animal and human tissues (15–30% of sum PCB) [30], [31].

The aim of the study was to investigate if doses of PCB 153 and PCB 126 comparable to exposures found in wild animals could produce effects in a controlled animal model. Possible adverse effects on the hypothalamic–pitutitary–gonadal axis were examined by measuring gonadotrophins and gonadal steroid hormone concentrations in a goat-kid model where the mothers were orally dosed PCB from day 60 of gestation until delivery. The goat kids were thus exposed in late gestation and in the suckling period, whereas female sexual function was studied during adolescence.