Inadequate nutrition compromises fetal development and poses long-term health risks for the offspring, even without decreased birth weight. The present study sought to 1) establish the ontogeny of fetal renal glomerulus number (GN) in sheep and 2) evaluate the effects of 50% global nutrient restriction (NR) during early to midgestation on GN and the renin-angiotensin system in the fetal kidney. GN increased from 78 dG (68,560 Ϯ 3802) to 135 dG (586,118 Ϯ 25,792). NR increased combined kidney weight (29 Ϯ 0.6 g versus 23 Ϯ 1.1 g), whereas decreased GN relative to right kidney weight approached significance in males (26,000 Ϯ 5300 versus 39,000 Ϯ 2800 GN/g) compared with control (C) males and females. NR decreased immunoreactive angiotensin II (Ang II) type 1 receptor (AT1) in the NR kidneys at 78 dG and increased renin at 135 dG. Immunoreactive renin decreased from 78 to 135 dG. Female fetuses had more immunoreactive Ang II type 2 receptor (AT2) than male fetuses at 78 dG and males had more AT1 at 135 dG. The present study demonstrates gender-specific differences in fetal growth and development and in fetal kidney development in pregnancies affected by NR. T he American Kidney Foundation estimates the rates of chronic renal diseases are increasing rapidly, such that 20 million Americans (one in nine adults) have some form of chronic renal disease. Similarly, epidemiologic and animal studies showing a developmental origin for renal dysfunction are also increasing (1-3). This growing body of evidence clearly shows that the kidney is sensitive to perturbations of the fetal environment. Viewed in concert with factors in modern society that may collude to impair fetal nutrition, such as poverty and drug abuse, and clinical conditions, such as hyperemesis gravidarum, anorexia nervosa, and bulimia, it is clear that decreased nutrient delivery to the fetus will affect a large number of pregnancies across socioeconomic strata (4 -6).The acquisition of renal GN is a morphogenic process that reflects sensitivity to a suboptimal intrauterine environment (7,8). Reduced GN has been shown when fetal growth restriction begins early in gestation but not when the insult is restricted to late gestation (9). Interestingly, a reduction in GN following uninephrectomy during fetal life is strongly associated with increased postnatal blood pressure (10,11), whereas adult uninephrectomy is not (12). Factors that affect nephrogenesis during fetal life therefore appear to have a greater impact on blood pressure than the hypertrophic responses induced in the adult to facilitate the maintenance of filtration surface area. In accordance with this perspective, we have recently demonstrated decreased GN associated with hypertension in the male offspring of sheep NR from early to midgestation (7). From these and other studies, it is clear that although the period in which kidney development may be affected is broad, late gestation is not a part of the critical nephrogenic window in large animals such as sheep (7,9,13,14).Previous studi...