doi: 10.1006/ scdb.2000.0157, available online at http:/ / www.idealibrary.com on seminars in CELL & DEVELOPMENTAL BIOLOGY, Vol. 11, 2000: pp. 115–125 Maternal influences on placental development John Aplin Epidemiological evidence suggests that size at birth may affect health in later life. The growth of the fetus may be adversely affected by a suboptimal maternal environment. Understand- ing placental development and function will help unravel the mechanisms controlling fetal growth. This article poses the problem: how does the maternal environment (uterine or systemic) influence placental development? Critical human placental functions includeremodelling maternal uterinespi- ral arteries to increase the flow of blood to the maternofetal interface, and transferring oxygen and nutrients into the fetal vasculature, all processes involving trophoblast. Gene ablations that affect pregnancy outcome in mice lead to some interesting hypotheses. Key words: trophoblast / decidua / invasion / differentia- tion / human c  2000 Academic Press Fetal programming STUDIES PUBLISHED OVER THE last decade have corre- lated birth weight and dimensions with health indices in later life, and the suggestion has emerged that smaller babies may be at higher risk of cardiovascular disease and diabetes as adults. This has led to the hypothesis that the fetus adapts to stress in utero, resetting irreversibly critical metabolic controls. 1, 2 The immediate effect is to prevent the fullest expres- sion of the growth potential of the fetus, with longer term effects on metabolism and homeostasis. Data from animal models strongly support the general Dr John Aplin, Research Floor, St Mary’s Hospital, Manchester M13 0JH, UK. E-mail: John.Aplin@man.ac.uk From the Academic Unit of Obstetrics and Gynaecology, School of Medicine and School of Biological Sciences, University of Manchester, UK. c 2000 Academic Press 1084–9521 / 00 / 000115+ 11 / $35.00 / 0 concept. Thus, for example, when pregnant rats are fed a restricted diet, their offspring show elevated blood pressure in adult life. 3 Since cardiovascular disease and diabetes normally occur in later life, this type of adaptation would not be expected strongly to affect the reproductive fitness of the population. The underlying cellular and molecular mechanisms are unclear, though the role of maternal glucocorticoids, which are normally prevented from reaching the fetus as a result of being converted to cortisone by placental 11β hydroxysteroid dehydrogenase type 2, is under close scrutiny. 4, 5 A clear understanding of placental function is critical in any analysis of fetal programming. In human, implantation is interstitial, and the primary maternofetalinterface ishaemochorial,with maternal blood circulating over the apical syncytiotrophoblast surface. The mouse is also an interstitially implanting species with a haemochorial placenta, and though there are very important differences of decidual and placental anatomy between mice and women, gene knockouts with placental or uterine phenotypes serve to help develop hypotheses to explain programming (see Cross, this volume). To what extent can the maternal environment affect pregnancy outcome? There are opposing points of viewregarding the abil- ityofthe uterine environment to modulate pregnancy outcome. 6 One extreme position is that the placenta develops according to an intrinsic programme acti- vated at fertilisation, requiring only a physical sup- port, normal homeostatic mechanisms and access to the maternal blood supplyfor its full expression. The relatively normal histology of the placenta in ectopic pregnancyis often cited in support of this argument, since it implies that the abdominal cavity or Fallopian tube isjust assuitable an environment for placentation as the uterus. 7 In this case, the maternal host is a ‘pas- sive altruistic bystander that accommodates itself to 115