In utero exposure to environmental chemicals: lessons from maternal cigarette smoking and its effects on gonad development and puberty

Rebecca McKinlay, Peter J. O'Shaughnessy, Richard M Sharpe, Paul Alfred Francois Fowler

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)

1 Citation (Scopus)


Although tobacco use has declined in recent years, a signifi cant minority
of pregnant women still smoke and cessation during gestation is rare. Substantial
passive exposure to tobacco smoke is an unavoidable hazard to many more. This is
of great concern, since tobacco smoke contains a large number of toxins known to
be hazardous to foetal development. These include carbon monoxide, nicotine and
its breakdown products, polycyclic aromatic hydrocarbons, thiocyanate and many
more. Some are known or suspected endocrine-disrupting chemicals (EDCs).
In addition to providing further evidence to dissuade pregnant women and those
around them from smoking, studying the effects of tobacco smoke on human development
gives insight into effects of other EDCs and EDC mixtures which affect the
same developmental processes and end points.
In utero development of the reproductive tract is a poorly understood process that
is entirely dependent on the proper functioning of the maternal and foetal endocrine
systems. It is vulnerable to disruption in both genders. Thus far, only the physiological
effects of the disruption of oestrogen and androgen-mediated signalling and the
hypothalamic-pituitary-gonadal (HPG) axis have been investigated in detail. Our
knowledge of the process in both animals and humans is far from complete. Exposure
of animal models to EDCs affecting sex steroid-mediated processes can cause a wide range of adverse reproductive outcomes. These include impaired gametogenesis
and later subfertility, early reproductive senescence, neuroendocrine dysregulation
affecting fertility and sexual behaviour, genital deformities and increased susceptibility
to certain cancers. Effects on humans are thus far uncertain, but many epidemiological
studies have associated EDC exposure with decreasing fertility, reductions in the age
of pubertal onset and increases in susceptibility to certain cancers and deformities
of the reproductive tract. Studies of the physiological and cellular effects of individual
EDCs and EDC mixtures in vitro and in vivo have added plausibility to these
Prenatal human tobacco smoke exposure has multiple known adverse effects on
reproductive development and may affect the age of puberty in females at least.
Overall, maternal and foetal oestrogen and androgen synthesis are suppressed centrally
by suppression of the HPG axis by the activation of the hypothalamic-pituitary-
adrenal (HPA) axis and peripherally by the direct inhibition of their synthesis.
The hypothalamic-pituitary-thyroid (HPT) axis and the peripheral transformation
and utilization of thyroid hormones are also suppressed by activation of the HPA
axis. Neuroendocrine programming of the HPA, HPT and HPG is perturbed.
Decreased fertility and fecundity have been noted in both genders, and exposed
females are more likely to experience early menopause. Some epidemiological
studies have reported a connection with malformations of the male reproductive
tract (testicular dysgenesis syndrome), the plausibility of which is supported by
evidence that the production of desert hedgehog, a morphogen essential for male
sexual development, is halved by maternal smoking. These outcomes are similar to
those observed in epidemiological and animal studies of other EDCs and EDC mixtures,
but a great deal of further research is required to determine their exact physiological
effects and properly quantify the risks they pose. The effects of tobacco
smoke and other EDC mixtures and EDCs on systems other than those directly
mediated by the oestrogen receptors and androgen receptor have barely begun to be
Original languageEnglish
Title of host publicationEndocrine Disruptors and Puberty
Subtitle of host publicationContemporary Endocrinology
EditorsEvanthia Diamanti-Kandarakis, Andrea Gore
PublisherHumana Press
Number of pages48
ISBN (Electronic)978-1-60761-561-3
ISBN (Print)978-1-60761-560-6
Publication statusPublished - 2012

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