It has been demonstrated that kidney growth and nephrogenesis are each regulated by intrarenal factors, including the insulin-like growth factors, glucocorticoids, and the renin-angiotensin system. Therefore, we have investigated the impact of periconceptional undernutrition (PCUN; from ϳ6 wk before to 7 days after conception) in singleton (control, n ϭ 18; PCUN, n ϭ 16) and twin pregnancies (control, n ϭ 6; PCUN, n ϭ 5) on the renal mRNA expression of 11-hydroxysteroid dehydrogensase type 1 and type 2 (11-HSD-1 and -2), the glucocorticoid (GR), and mineralocorticoid receptors, angiotensinogen, angiotensin receptor type 1 (AT1R) and 2 (AT2R), IGF-1 and IGF-2, and IGF1R and IGF2R at ϳ55 days gestation. There was no effect of PCUN or fetal number on fetal weight on relative kidney weight at approximately day 55 of gestation. There was an inverse relationship between the relative weight of the fetal kidney at approximately day 55 and maternal weight loss during the periconceptional period in fetuses exposed to PCUN. Exposure to PCUN resulted in a higher expression of IGF1 in the fetal kidney in singleton and twin pregnancies. Being a twin resulted in higher intrarenal expression of IGF-1 and IGF-2, GR, angiotensinogen, AT1R, and AT2R mRNA at 55 days gestation. Renal 11-HSD-2 mRNA expression was higher in PCUN singletons, but not PCUN twins, compared with controls. Thus, there may be an adaptive response in the kidney to the early environment of a twin pregnancy, which precedes the fetal growth restriction that occurs later in pregnancy. The kidney of the twin fetus exposed to periconceptional undernutrition may also be less protected from the consequences of glucocorticoid exposure. nutrition; pregnancy; renal; hypertension A SERIES OF CLINICAL AND EXPERIMENTAL studies have shown that maternal nutrition and placental substrate supply during pregnancy are each important in determining the pattern of fetal kidney growth and the functional capacity of the kidney and cardiovascular system in postnatal life (23,28). In the human, nephrogenesis is complete by 32-34 wk of gestation and a nephron deficit present at birth will, therefore, persist through life (23, 28). Kidney growth is significantly slower in the intrauterine growth-restricted (IUGR) human fetus, and total nephron number is also lower in the IUGR fetus compared with normally grown fetuses (14,15,21). In the sheep, twinning, a naturally occurring form of fetal growth restriction, results in a ϳ40% lower nephron endowment compared with singleton fetuses (25). Similarly in the rat, maternal protein restriction throughout pregnancy or induction of uteroplacental insufficiency results in a decrease in kidney growth and in the number of nephrons (2,17,24,35,40,44). A low-protein diet throughout pregnancy in the rat also programs an upregulation of the renal glucocorticoid receptor (GR) and separately, administration of glucocorticoids at 15-16 days of gestation results in a reduction in glomerular number and hypertension (32,33). It has been proposed that ther...