ABSTRACT
Polyunsaturated fatty acids (PUFA) are important in pregnancy, fetal development and parturition. We measured free fatty acids (FFA), albumin and alpha-fetoprotein (AFP) in the maternal and fetal circulations of women undergoing elective Caesarean section at term. We also studied the impact of PUFAs on estrogen (ER) and progesterone receptors (PR) binding properties in vitro in the myometria of pregnant women and ex vivo in human myometrial cells in culture. FFA in intervillous blood (I) (feto-maternal interface) and maternal peripheral blood (M) were similar, while those in the umbilical vein (V) and arteries (A) were 2-4 fold lower (P<0.001). PUFA levels were low in M and 3 fold higher in I, A and V (P< 0.001); consequently C20:4 and C22:6 were most abundant in intervillous space. Albumin was uniformly distributed throughout the maternal-fetal unit, but there was a transplacental gradient in AFP. The AFP in the intervillous space had a special conformation (less immuno-reactive, more anionic), suggesting loading with PUFA. Physiological concentrations of C20:4 stimulated estradiol binding, but inhibited progestin binding. C20:4 inhibited progesterone binding by decreasing the number of binding sites, with no change in apparent affinity, in vitro in myometrial tissue and ex vivo in myometrial cells. Thus PUFA may modulate the steroid hormone message, so that the high C20:4 concentration at the maternal-fetal interface at term may help amplify the estrogen signal and inhibit the progesterone signal.
Subject(s)
Estrogens/metabolism , Fatty Acids, Unsaturated/blood , Maternal-Fetal Exchange/physiology , Neoplasm Proteins , Progesterone/metabolism , Tumor Suppressor Proteins , alpha-Fetoproteins/metabolism , Carrier Proteins/blood , Cells, Cultured , Estrogens/physiology , Fatty Acid-Binding Protein 7 , Fatty Acid-Binding Proteins , Fatty Acids, Nonesterified/blood , Female , Humans , Myelin P2 Protein/blood , Myometrium/metabolism , Pregnancy , Progesterone/physiology , Protein Binding , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Serum Albumin/metabolism , Signal Transduction/physiologyABSTRACT
Polyunsaturated fatty acids (PUFA) like arachidonic (C20:4) and docosahexaenoic (C22:6) acids are essential for harmonious fetal development. This study evaluates, at near term, the distributions of free fatty acids (FFA) and their fetal carrier protein, alpha-fetoprotein (AFP) in the maternal (M) and fetal circulation (umbilical arteries (A) and vein (V)), focusing on the feto-material interface where maternal intervillous blood (I) contacts the fetal trophoblast. FFA concentrations in intervillous and maternal blood were similar, while those in umbilical arteries and vein were 2- to 4-fold lower (P < 0.001). There were more saturated FFA in umbilical vein (41%) and arteries (44%) blood than in maternal (30%) and intervillous (32%) blood (P < 0.001). Monounsaturated FFA predominated (P < 0.001) in maternal (43%) blood, but not in intervillous (35%), umbilical vein (33%) and arteries (31%) blood. Di-triunsaturated FFA were similar in intervillous and maternal (25%) blood and lower in umbilical vein and arteries (16%) (P < 0.001). PUFA were low in maternal (2.5%) blood and higher in intervillous and umbilical vein and arteries (9%, P < 0.001); consequently, C20:4 (40 microM) and C22:6 (16 microM) were the most abundant in the intervillous space. The AFP concentrations and AFP lectin-reactive isoforms were similar in intervillous and umbilical vein and arteries blood, but immuno-electrophoresis revealed a particular AFP conformation (less immuno-reactive, more anionic) in the intervillous space, suggesting that AFP is heavily loaded with PUFA at the feto-maternal interface. Prostacyclin derived from C20:4 was similar in all compartments but the thromboxane A2 concentration was 10-fold higher in intervillous blood than in maternal and umbilical vein and arteries blood. Thus the feto-maternal interface has a specific pattern of cell signalling molecules that might critically influence parturition.
