Exploring Methods of Human Placental Function
The comparison of maternal and fetal (umbilical cord) blood levels of any substance or medicine provides information on their concentrations at a particular time point of gestation after delivery. The obtained values do not indicate the mechanism by which the transfer rate and direction occurred between maternal and fetal compartments. Intermammalian species show that the structure,[9,10] transport and endocrine functions of the placenta are strongly varied compared with other organs. In addition, differences in fetal susceptibility to teratogens also exist between species[13–15] as do rates and extent of fetal development during pregnancy. The animal species that most closely mimic human placental characteristics have a hemochorial histological organization, such as rodents and, primarily, primates. Clearly, primates would be the species of choice, but they are expensive and can be difficult to work with, so rats and mice are more commonly used. While the human placenta is hemomonochorial in classification, composed of a single layer of trophoblast (syncytium) in direct contact with the maternal blood, rats and mice have three trophoblast layers (hemotrichorial) in a labyrinthine placenta.[16,17] This anatomical difference is reflected by different diffusion patterns between maternal and fetal circulations, with concomitant differences in permeability to various substances. A review by Moffett and Loke demonstrated that differences in the immunological reaction exist between the two species. The placental endocrine functions differ very strongly between mice and humans. In addition, in humans, the yolk sac is present only very early in pregnancy, whereas in rodents it persists throughout gestation, encloses the fetus and performs important transport functions. For example, the transfer of IgG and its subclasses from the maternal to the fetal circulations in humans occurs via Fc receptors (FcRs) in the placenta, which can be readily demonstrated using ex vivo perfusion, while in mice the yolk sac is the organ responsible for IgG materno–fetal transport.[21,22] The weight ratio of the fetus to the placenta in the mouse reaches 30:1 at birth, which is significantly higher than that of man, which reaches 6:1 at delivery. The higher ratio rate shown for the smaller placenta of the mouse demonstrates that the smaller placenta in rodents can more efficiently nourish the fetus than the large placenta in humans.
The placental perfusion technique began in the 1960s allowing the study of tissue functions under ex vivo conditions.[24–26] The first described perfusion method of the isolated human placental cotyledon was reported in 1967 by Panigel et al., and in 1970, Nesbitt et al. introduced the dual perfusion model including both maternal and fetal circuits in an apparatus.
The easy availability of the human placental tissue with its known biological resistance to hypoxia and ischemia allows the tissue to be suitable for clinical research invitro.[29,30] However, these investigations with placental tissue at delivery (with mature organs) have certain limitations, because the provided information may not reflect the structure and biological function of the placenta earlier in gestation. Therefore multiple models, such as cells and tissue explants cultured from various placental layers and gestational age, and ex vivo perfusion of human placental tissues at term, have been used to explore a wide variety of functions such as cellular proliferation and differentiation, endocrine function as well as permeability with hormone production, drug transport and mechanism with determination of the influx and efflux transfer direction, and metabolism.[31,32] The ex vivo perfusion model allows the study of these parameters in the presence of different substances and medicines, as well as of the drug kinetic profile and the chemical action on the placental tissue, which are difficult to obtain under in vivo conditions.[31,32] This method has been used in the last 40 years to study the transfer of many substances such as nutrients, hormones, proteins, therapeutic agents and drugs of abuse, and offers an extremely useful tool for therapeutic drug development.[31,32] The increasing demand of the clinicians to reach better decisions about which medicine should be used with the optimal dosage regimens in pregnancy to minimize the fetal exposure and toxicity could be drawn from experimental data on placental drugs investigated using the ex vivo placental perfusion model.[31,32]
Expert Rev Clin Immunol. 2013;9(3):235-249. © 2013 Expert Reviews Ltd.