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.

Carrier Proteins↗

PubMedDate not supplied

Alpha-fetoprotein gene expression in early and full-term human trophoblast.

Alpha-fetoprotein (AFP) is a major serum glycoprotein synthesized during fetal life mainly by the yolk sac and the fetal liver. At term, it reaches high concentrations in the maternal intervillous blood, which is in direct contact with the placental trophoblastic microvillous membrane, and this suggests the placental origin of the AFP at the fetal-maternal interface. We used several experimental approaches to investigate the expression of AFP gene and fetal protein production in early gestation and term placentas. RT-PCR and immunological studies clearly identified AFP messenger RNA and AFP protein in the placental villi from first trimester of pregnancy. The AFP gene was also expressed in highly purified cytotrophoblasts from early placentas, and enzymo-immunoassay showed that AFP protein was synthesized and secreted by early cytotrophoblasts. AFP was also detected in the cytoplasm of these cells by immuno-cytochemistry. However, none of these methods detected any expression of the AFP gene in full-term placental villi or in cultured trophoblasts. These findings demonstrate that both AFP mRNA and protein are present in trophoblastic cells early in pregnancy. The absence of AFP gene expression in term placental villi also suggests, that the AFP at the fetal-maternal interface is attributable to a notable transplacental passage of AFP from fetal blood in late pregnancy.

Adult↗

PubMedDate not supplied

The physicochemical and biological properties of alpha-fetoprotein depend of its ligand environment.

The majority of studies have concentrated on the endocrine and immunological roles of alpha-fetoprotein (AFP). These studies have been strongly orientated and sustained by research showing that rat and mouse AFPs competitively bind estrogen and non-esterified fatty acids. AFPs of other species, such as humans, are not estrogenophilic but all those studied to date bind NEFAs tightly. Endogenous ligands can greatly influence the conformation of the protein and consequently its biological activity. AFP may have three possible mechanisms of action: a) Murine AFP may be a modulatory element of estrogen expression which determines, under the control of NEFAs the concentration of the active free steroid. b) The protein could be transformed by bound ligands, so enhancing or inhibiting its binding to a target cell receptor, and consequently modifying its biological activity. AFP per se, can be the regulatory element. c) AFPs of all species can work as fatty acid binding proteins and modulate the availability of free NEFAs (not bound to protein). These free NEFAs can, in turn, act positively or negatively on various proteins involved in the pathways of the transfer of the steroid and peptide informations leading to cell multiplication or differentiation.

Animals↗