Human Reproduction Update Advance Access published online on June 13, 2008
Human Reproduction Update, doi:10.1093/humupd/dmn021
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Potential significance of physiological and pharmacological glucocorticoids in early pregnancy
1 Centre for Developmental and Endocrine Signalling, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, St George's University of London, Cranmer Terrace, London SW17 0RE, UK 2 Fetal Medicine Unit, Academic Section of Obstetrics and Gynaecology, Division of Clinical Developmental Sciences, St George's University of London, Cranmer Terrace, London SW17 0RE, UK
To whom correspondence should be addressed at: Correspondence address. Tel: +44-20-8725-5961; Fax: +44-20-8725-5958; E-mail: aemichae{at}sgul.ac.uk
BACKGROUND: Despite extensive studies of the developmental consequences of increased glucocorticoid exposure in mid- to late pregnancy, relatively little is known regarding the significance of glucocorticoids in early pregnancy. The objective of this review was to consider potential roles for this family of corticosteroids that might relate to early pregnancy.
METHODS: Although this is a narrative review, 249 source articles addressing potential effects of glucocorticoids on aspects of early pregnancy and development (published between 1997 and 2007) were identified using a systematic literature search. Additional articles (115) were identified if cited by the primary reference articles identified in the systematic phase of the review.
RESULTS: Much of the evidence to implicate glucocorticoids in early pregnancy comes from studies of steroid receptors and the 11β-hydroxysteroid dehydrogenase enzymes, which modulate cortisol action in the endometrium/decidua, trophoblast, placenta and embryo/fetus. The evidence reviewed suggests that in early pregnancy the actions of glucocorticoids are balanced between positive effects that would promote pregnancy (e.g. stimulation of hCG secretion, suppression of uterine natural killer cells, and promotion of trophoblast growth/invasion) versus adverse effects that would be expected to compromise the pregnancy (e.g. inhibition of cytokine-prostaglandin signalling, restriction of trophoblast invasion following up-regulation of plasminogen activation inhibitor-1, induction of apoptosis, and inhibition of embryonic and placental growth).
CONCLUSIONS: Glucocorticoids exert many actions that could impact both negatively and positively on key aspects of early pregnancy. These steroids may also be implicated in obstetric complications, including intra-uterine growth restriction, pre-term labour, pre-eclampsia and chorio-aminionitis.
Key words: cortisol / glucocorticoid / 11β-hydroxysteroid dehydrogenase / placenta / trophoblast
Received on December 13, 2007; revised April 11, 2008; accepted on April 24, 2008