Beyond The Abstract - Maternal Smoking During Pregnancy Specifically Reduces Human Fetal Desert Hedgehog Gene Expression During Testis Development
UroToday.com - In this article, published in the Journal of Clinical Endocrinology and Metabolism, Fowler and colleagues report that continued cigarette smoking by women with normally progressing pregnancies nearly halves Desert hedgehog (DHH) gene expression in the testes of second trimester fetuses. Expression of 29 other key testis genes and testis cell numbers were not significantly affected but circulating fetal testosterone tended to be reduced if the mother smoked.
Desert hedgehog is important in regulating fetal testis development and in both knock-out mouse models and men with spontaneous mutations in the gene, the testis is highly abnormal and the individual infertile. While this demonstrates the severe effect of gene ablation, reduction in expression is likely to have more subtle effects. This leads to the conclusion that increased incidences of cryptorchidism, hypospadias and subnormal testis development and fertility associated with maternal cigarette smoke by many studies could be explained, at least partially, by reduced DHH signalling in the developing testis.
The identity of culprit chemical(s) in cigarette smoke involved in the reduced testis DHH expression is/are not clear. Concentrations of 16 PAHs (polycyclic aromatic hydrocarbons, one of the well know classes of cigarette smoke chemicals) in the livers of the fetuses were not individually significantly different in fetuses from smokers. However, the levels were higher than those reported for smokers' lungs and were highly significant in discriminant analysis, correctly categorising fetuses to smoking and non-smoking groups. The results are suggestive with respect to the effects of environmental chemicals and endocrine disrupting compounds more generally. These potentially harmful chemicals enter the body through a wider variety of routes, particularly via ingestion, that those in cigarette smoke. Nevertheless, maternal smoking provides one, fairly extreme, form of insult, which can help us to understand the effects of endocrine disruption on the fetus more generally.
Related papers and more detailed methodology elsewhere
1. Supplementary methodology: