HIV AND THE PLACENTA

The placenta provides nutrients and removes wastes from the fetus through various mechanisms of transfer, diffusion, carrier-mediated transport and active transport, and vesicular transfer. 14 In humans the placental barrier is hemochorial (i.e., the placental trophoblast surface is in direct contact with the maternal blood, forming the maternal–fetal interface). The fertilized ovum implants directly into the maternal endometrium within a week of fertilization. Anchoring villi form at the end of the fourth postmenstrual week. Specialized invasive trophoblasts, at the tips of the cytotrophoblast columns of the anchoring villi, invade maternal spiral arterioles of the endometrium and the inner third of the myometrium. This vascular adaptation is noted as early as 16 days after ovulation. 21 Communication between the developing intervillous space surrounding the villi and maternal blood supply is established by day 11 or 12, after ovulation. However, large amounts of maternal blood do not enter into the intervillous space until 8 weeks later. 32 The intervillous space, at term, holds approximately 400 to 500 mL of blood. 14,192 The trophoblast is an ectodermal covering of each villus. The villous barrier varies in thickness throughout gestation, initially being composed of syncytiotrophoblast, cytotrophoblast, and connective tissue stroma. Discontinuities begin to form in the syncytiotrophoblast layer at 9 to 12 weeks after menstruation. 145 Cytotrophoblast covers 50% only of the villous circumference in the second trimester and diminishes to 20% at term. 14 The formation of syncytial knots and vasculosyncytial membranes (VSM) beginning at 18 to 20 weeks gestation brings the fetal capillary in very close approximation to the maternal blood. The percentage of villous surface occupied by VSM varies from 0% at 12 weeks to nearly 30% at term. 71 The VSM constitutes the effective metabolic barrier between the fetal and maternal circulations and is composed of syncytiotrophoblast cytoplasm, trophoblast basement membrane, stromal connective tissue, vascular basement membrane, and capillary endothelium (Fig. 1). The VSM becomes progressively thinner, measuring 1 to 3 μm at term, finally resulting in fusion of the capillary and trophoblast basement membrane. 14 The placental membranes are multilayered, composed of tissues from the inner cell mass (amnion), the trophoblast shell (chorionic mesoderm), with intervening connective tissue from the extraembryonic mesoderm. The chorion of the free membranes (chorion laeve) is intimately attached to the maternal decidua (Fig. 2). Decidua, the endometrial stromal fibroblast, under progestational influences becomes apparent by the 28th day after menstruation and completely surrounds the implanted blastocyst. With growth of the gestational sac, there is obliteration of the uterine cavity as a feto-maternal tissue junction is established around the whole conceptus at 17 weeks after menstruation. The decidua at the base of the placenta comes into direct contact with the invasive fetal trophoblast of the anchoring villi (Fig. 3). At this interface there is extensive mingling of fetal and maternal cells. The fetal trophoblast and maternal decidua are partially separated by a layer of fibrinoid. Increased fibrosis and acute or chronic inflammation may be seen with the implantation site particularly within basal villi. 71 Hofbauer cells are phagocytic cells of mesenchymal origin found in the stroma of villi, chorion, and amnion. They are present in the villi from the fourth week after ovulation, prior to the development of a bone marrow. They maintain their ability to undergo mitosis and self-replicate, in contrast to bone marrow-derived macrophages. These cells are relatively constant throughout gestation, comprise about 40% of the stromal cells, 76 and express the leukocyte antigens, CD4, CD45, CD68, and CD1a. 14,143