Mechanisms of alphafetoprotein transfer in the perfused human placental cotyledon from uncomplicated pregnancy.

Abstract

We investigated the mechanisms of alphafetoprotein (AFP) transfer across the human placenta by correlating measurements of AFP transfer with cytochemical localization of AFP. Placental cotyledons were dually perfused in vitro with either the fetal or maternal perfusate containing umbilical cord plasma as a source of AFP. Steady state AFP clearance, corrected for release of endogenous AFP, was 0.973 +/- 0.292 microliter/min per gram in the fetal to maternal direction (n = 10), significantly higher (P < 0.02) than that in the maternal to fetal direction (n = 5; 0.022 +/- 0.013 microliter/min per gram). Clearance of a similarly sized protein, horseradish peroxidase was also asymmetric but clearance of the small tracer creatinine was not. Using a monoclonal antibody, we localized AFP to fibrinoid deposits in regions of villi with discontinuities of the syncytiotrophoblast, to cytotrophoblast cells in these deposits, to syncytiotrophoblast on some villi, and to trophoblast cells in the decidua. We conclude that AFP transfer in the placenta is asymmetric and that there are two available pathways for AFP transfer: (a) from the fetal circulation into the villous core and across fibrinoid deposits at discontinuities in the villous syncytiotrophoblast to enter the maternal circulation; and (b) AFP present in the decidua could enter vessels that traverse the basal plate.

Direct Evidence for Transplacental Allergen Transfer

“…These papers have shown in common that priming of fetal lymphocytes occurs ubiquitously irrespective of a particular allergen dose. In human placenta investigations, it has been shown previously that alpha-fetoprotein readily crosses the placenta barrier, with a net permeability increase from the fetal to maternal circulation (23). As the permeability of alpha-fetoprotein was proportional to the coefficient of free diffusion in water, a transfer by paracellular diffusion was postulated.…”

The placenta: a multifaceted, transient organ

“…In this context, the plaques represent a possible route for the diffusion of hydrophilic molecules, whereas in broader terms they may also be potential portals for the ingress of maternal immune cells and the vertical transmission of pathogens. Immunohistochemical studies have localized transfer of alpha-fetoprotein to these sites [19], suggesting they may play a significant role physiologically.…”

Placental nutrient supply and fetal growth

“…The pores may be transtrophoblastic channels, which have been visualised in both the guinea pig and human placenta (Kaufmann et al, 1982;Kertschanska et al, 1994). Alternatively, a paracellular pathway may be provided during denudation of the syncytiotrophoblast (Brownbill et al, 1995;Brownbill et al, 2000;Edwards et al, 1993). This is a normal feature of the human placenta at all stages of gestation and the denudations are either open or filled with fibrinoid deposits (Nelson et al, 1990).…”

“…1). The fetal capillary endothelium is of the continuous type and allows unrestricted passage of small solutes within the interendothelial clefts but diffusion of small peptides and larger sized molecules through these clefts will be restricted to an extent related to their molecular radius (Brownbill et al, 1995;Eaton et al, 1993;Firth et al, 1983;Leach and Firth, 1992;Michel and Neal, 1999;Sibley et al, 1982). The issues of solute permeability will be discussed further below.…”