In vivo investigation of placental transfer early in human pregnancy

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Abstract

The use of coelocentesis to study placental drug transfer in the first trimester has required the adaptation of existing pharmacologic models to the changing anatomical structures present before and after 12 weeks of gestation. The biochemical properties of the coelomic and amniotic fluids are important parameters in evaluating the pharmacokinetics of drugs and toxins in early pregnancy. In particular, the protein concentration and pH of these fluids are significantly different and vary widely with gestational age. These biochemical variations are less likely to influence the distribution of inert substances such as inulin inside the first trimester conception cavities than the distribution of drugs such as diazepam or propofol. This can explain why they are not all accumulating inside the exocoelomic cavity. It has been demonstrated that the permeability of the placenta is greater in early pregnancy than at term. Furthermore, because of the slow turn-over of the coelomic fluid, substances such as nicotine to which the mother is chronically exposed accumulate inside the exocoelomic cavity. This prolonged fetal exposure to tobacco carcinogens has important teratogenic implications and should be further explored.

Introduction

Intravaginal high-resolution ultrasound transducers have provided the optimal visualisation of early anatomic structures of the human embryo and its environment. During most of the first trimester, the human fetus is surrounded by two fluid cavities separated by a thin membrane (Fig. 1). The inner cavity or amniotic cavity is formed during the third week of pregnancy from the inner cell mass of the implanted blastocyst [1]. The outer cavity or extra-embryonic coelomic cavity develops during the 4th week of gestation within the extraembryonic mesoderm situated adjacent to the trophoblast from which it is probably derived. The amniotic cavity contains the developing fetus whereas the coelomic cavity contains the secondary yolk sac which is directly connected to both the fetal gut and the dorsal aorta by the vitelline duct. The amniotic membrane floats freely between these fluid cavities until it fuses with the placental chorionic plate by the end of the first trimester (Fig. 2).

At approximately 31 days menstrual age, the gestational sac has a size of 2–3 mm in diameter. The primitive placenta and the exocoelomic cavity are the first embryological structures detectable by means of transvaginal ultrasound imaging during the 5th week of gestation. The amniotic cavity is smaller than the exocoelomic cavity up to 9 weeks of gestation [2]. Coelomic and amniotic fluid can be selectively retrieved by transvaginal puncture [3], [4]. The exocoelomic cavity was probably the last remaining physiological body fluid cavity to be explored in the human embryo. The selective sampling of fluid from the exocoelomic cavity has also offered a novel approach to the study of drug and toxin transfer across the early human placenta.

Section snippets

Technique of coelocentesis

Selective embryonic fluid aspiration can only be performed under ultrasonographic guidance using a transvaginal probe through a needle guide attached to the shaft of the probe. When the two compartments are clearly visualised, coelomic fluid is first aspirated using a 20-gauge needle (Fig. 3). Subsequently, a second 20-gauge needle is reintroduced through the guide and the needle advanced into the amniotic cavity to aspirate amniotic fluid.

The exocoelomic cavity can be visualised from the 5th

Embryonic fluid biochemistry

The unique anatomical position of the exocoelomic cavity has enabled us to study the protein metabolism of the early placenta and the secondary yolk sac and to explore materno-embryonic transfer pathways. There is no anatomical barrier between the mesenchyme of the placental chorionic plate and the exocoelomic cavity in early pregnancy. Since the conceptus is completely surrounded by chorionic villi, later to form the placenta and the chorion laeve, biological substances present in the maternal

In vivo study of drug transfer early in human pregnancy

Placental transfers have been studied mainly in experimental animals such as guinea pigs and monkeys because they have haemochorial placentation similar to the human. Due to the complexity of the experimental situation in the intact animal and the considerable embryological differences between human and some animal species, the precise mechanism of transfer of many substances across the human placenta cannot be entirely elucidated in those models. Until recently placental transfers in humans

Conclusions

The unique anatomical position of the exocoelomic cavity has enabled us to study the protein metabolism of the early placenta and secondary yolk sac and to explore materno-embryonic transfer pathways. However, the use of coelomic fluid sampling to study placental transfer requires the development of different pharmacologic models based on specific anatomical differences existing before and after 12 weeks of gestation. The biochemical properties of the different fluids are important parameters

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