Review
How can chemical compounds alter human fertility?

https://doi.org/10.1016/S0301-2115(01)00441-9Get rights and content

Abstract

The effects of environmental toxins, such as pesticides, solvents and industrial waste, on human and animal health have caused much public fear. The suggested mechanism of action for these xenobiotics is their capacity to interact with steroid hormones receptors, in particular those for estrogens and androgens. Concern was reinforced by the “historical” example of diethylstilbestrol, an estradiol mimetic causing genital cancer in girls exposed in utero. The real harm of these environmental xenobiotics is controversial. Some authors estimate that they do not reach sufficiently high concentrations to do damage and much experimental work has been done. In this review, we summarise the latest findings on the molecular mechanisms of action of three environmental toxicants, xenohormones, dioxin and glycol ethers and compare animal and cell experimental model data with epidemiological studies.

Introduction

In the past few years, several studies have pointed out the fact that chemical compounds, drugs, solvents and environmental pollutants could mimic or antagonise the effects of steroid hormones, like estrogens and androgens. These hormones have a crucial effect on the reproductive system, cellular homeostasis and development.

Some epidemiological studies suggested the occurrence of an alteration in the male reproductive function in the past 50 years, particularly a decrease in the sperm count and quality, an increase in the malformations frequency of the reproductive apparatus (cryporchidism and hypospadia) [1] and of testicular cancers [2], [3]. Xenohormones, dioxin and glycol ethers have been suspected to play a crucial and deleterious role in the alteration of human fertility, and the increase of the incidence of testicular and breast cancers. We will review their molecular mechanisms of action and correlate their effect on reproduction system via their effects on gene regulation, genotoxicity and cells transformation.

Section snippets

The first culprits: xenohormones

Xenohormones disruptors are compounds that mimic or antagonise the activity of steroid hormone. They are widespread used chemicals like pesticides (i.e. endosulfan, p,p′DDE, o,p DDT, chlordan, …) dyes and paintings (i.e. phenol red) or the degradation of plastic materials (i.e. bisphenol A). One of the most documented examples of a xenobiotic having hormonal activity is that of diethylstilbestrol. The discovery of the adverse effects of diethylstylbestrol (DES) constitutes the first proof that

Second culprit: dioxin

Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated dibenzo-p-dioxins, biphenyls, dibenzofurans, and related compounds represent a diverse group of persistent, widespread environmental contaminants. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin), the most biologically-active and toxic member of this class of compounds produces a wide variety of species- and tissue-specific effects [34], [35] including, tumour promotion, immuno-, hepato- and dermal-toxicity, lethality, birth

Metabolism and action

Glycol ethers are a class of organic colourless solvents that are miscible with water and many organic solvents [76]. This makes them useful for a wide variety of solvent applications in the manufacture of lacquers, paints, dyes, inks, cleaning agents and liquid soaps. Glycol ethers are divided into two families, the ethylene glycol derivatives (E group) and the propylene glycol derivatives (P group). These compounds are widely used, in 1988 the consumption of these products in western

Why are these chemical molecules are more dangerous than the corresponding hormones?

Several possible mechanisms can account for the toxicity of xenobiotic compounds that display hormonal activity. First, contamination by these compounds could occur at periods of development when the natural hormones are not secreted or are inactive. This could lead to an illegitimate activation of hormone receptors at a wrong time or place, and thus trigger developmental malformations. Second, natural steroid hormones bind to serum proteins, such as SSBG. These proteins are required to

Conclusion

The effects of xenoestrogens on human and animals remain controversial. DES is the only case where a direct relation between the noxious effects and the administration of the compound is well established. Other cases are based on observations of wildlife or in vitro studies. Considering the importance of the problem (increase in cancers and alteration of the fertility), several studies were initiated in order to explain the effects of the xenohormones, and to establish the mechanisms of action

Acknowledgements

We are grateful to Nancy MIONI for her technical assistance in typing this manuscript. We thank Laboratories Organon and Laboratory Benaı̈m for their financial support of this work.

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