The present study determined whether a developmental increase in placental low density lipoprotein (LDL) uptake occurred in baboon pregnancy, which was related to the increasing concentrations of estrogen typical of advancing gestation. LDL uptake was determined on collagenase-dispersed placental trophoblast cells purified via 50% Percoll gradient centrifugation and obtained from baboons between days 55-178 of gestation (i.e. the last two-thirds of gestation; term = 184 days). The majority of cells in the 50% Percoll-isolated fraction used to determine LDL uptake were syncytiotrophoblasts at all stages of gestation examined, as determined by immunohistochemical staining for syncytiotrophoblast-specific placental lactogen and pregnancy-specific-beta 1-glycoprotein. Placental LDL uptake, as determined by Scatchard analysis, increased progressively during the last two-thirds of gestation and was correlated (r = 0.87, P less than 0.001; curvilinear regression) with gestational age. Mean +/- SE LDL uptake early in pregnancy on days 55-58 was 1.9 +/- 0.2 ng/micrograms cell protein (n = 3). Placental LDL uptake (ng/microgram cell protein) at midgestation on days 94-104 (2.8 +/- 0.2; n = 5) increased to a value late in gestation on days 159-178 (14.6 +/- 1.0; n = 13), which was approximately 5-fold greater (P less than 0.001) than at midgestation, whereas uptake on days 128-138 was intermediate in value (8.3; n = 2) between the latter two periods. The apparent dissociation constant for placental LDL uptake was lower (P less than 0.01) at midgestation (0.33 micrograms/ml) than late in gestation (0.81 micrograms/ml). Placental LDL degradation, which depends on uptake, also increased with advancing stages of pregnancy, and was correlated (r = 0.74, P less than 0.01; curvilinear regression) with gestational age. Overall mean peripheral serum LDL cholesterol concentration was 46.5 +/- 1.7 mg/dl between days 50-170 of gestation. However, there was no significant change in serum LDL levels during this period. Maternal peripheral serum estradiol concentrations increased from 0.3 ng/ml on day 55 to an initial peak of approximately 3.5 ng/ml on days 70-80, then declined to approximately 1.0 ng/ml at midgestation. Estradiol then increased progressively throughout the remainder of pregnancy to maximal values of over 6 ng/ml late in gestation. In summary, there was a progressive increase in placental LDL uptake with advancing stages in the last two-thirds of baboon pregnancy, which was associated with a concomitant rise in maternal serum estradiol concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)