AMER. ZOOL., 32:331-342 (1992)
Comparative Studies of Structure and Function in
Mammalian Placentas with Special Reference to
Maternal-Fetal Transfer of Iron1
BARRY F. KING
Department of Cell Biology and Human Anatomy, School of Medicine,
University of California, Davis, California 95616-8643
SYNOPSIS. The mammalian chorioallantoic placenta is an extremely complex and structurally diverse organ. To better understand the placenta a number of classification schemes
have been devised. Classification on the basis of gross form or shape recognizes four major
categories—diffuse, cotyledonary, zonary and discoid. Another important classification scheme
is based on the number of tissue layers separating the maternal and fetal vascular systems
in the placenta. On this basis, three major types of placentas are recognized—epitheliochorial,
endotheliochorial and hemochorial. In many species, pathways in addition to the chorioallantoic placenta exist for maternal-fetal exchange. Some species have a yolk sac placenta
functioning concurrently with the chorioallantoic placenta whereas in some other species
exchange may occur across a chorioamnion. Some species have accessory or paraplacental
structures which function in nutrient exchange; these include hemophagous regions and
areolae. In the final sections, I review how these different structural specializations come
into play to accomplish a particular function, namely that of iron transfer to the fetus. There
are at least four different mechanisms by which different species accomplish iron transfer
to the fetus. These include 1) absorption of maternal transferrin-bound iron by the placenta;
2) absorption of iron by the yolk sac; 3) phagocytosis of maternal erythrocytes and 4)
absorption of iron-rich uterine secretions by accessory placental structures.
INTRODUCTION
The mammalian placenta is one of the
most structurally complex organs there is.
This complexity is brought about in part by
interaction of tissues of maternal and fetal
origin, by the presence of a variety of tissue
layers interposed between the maternal and
fetal vascular beds, and the changing relationships of these tissues and fetal membranes that occur between the time of blastocyst implantation and parturition. To
further complicate matters, considerable
species differences exist with regard to placental and fetal membrane structure. In this
brief survey of this very broad subject area
I have three basic objectives. First, I will
review some of the principles of placental
structure and classification in eutherian
mammals. Second, I will review how this
structural diversity needs to be taken into
account in understanding maternal-fetal
exchange in different species and even in a
single species. Third, I will review how this
structural diversity and complexity relates
to a particular function, namely that of iron
transfer to the fetus.
Classification of placentas
The definitive placenta of all eutherian
mammals is the chorioallantoic placenta. It
is classified as chorioallantoic since the chorion (trophoblast plus fetal mesoderm) is
vascularized by vessels derived from the
mesoderm of the allantoic stalk. Other types
of placental relationships also occur, one of
the most important being a yolk sac placenta. Over the years, a variety of classification schemes have been applied to the
placenta. Thus, the human chorioallantoic
placenta can be classified as discoidal because
of itsflatcircular shape, hemochorial because
of the tissue layers separating the maternal
and fetal blood streams, villous because of
the presence of villi, and deciduate because
maternal decidual tissue is shed at parturition along with the fetal placenta. In the
following sections, two of the classification
schemes for placentas will be explained; for
other classifications, see Ramsey (1982).
1
From the Symposium on Evolution ofViviparity in
Classification by gross form or shape. —
Vertebrates presented at the Annual Meeting of the
One
scheme for classifying placentas is by
American Society of Zoologists, 27-30 December 1990,
describing the distribution of outgrowths of
at San Antonio, Texas.
331
332
BARRY F. KING
DIFFUSE
ZONARY
DISCOID
COTYLEDONARY
FIG. 1. Major categories of placentas based on their gross form or shape. Diffuse placenta (e.g., pig); Cotyledonary
(e.g., sheep); Zonary (e.g., cat, dog) and Discoid (e.g., human, rodent). Figures redrawn and adapted from
Hamilton and Mossman (1972).
the chorion (chorionic villi or folds) on the
surface of the mature gestation sac. Using
this method, four major categories are recognized (Fig. 1). In a diffuse type of placenta,
projections (folds or villi) from the chorion
are distributed over most of the surface of
the gestation sac. This type is seen in a wide
range of animals including pig, horse, whale
and some primitive primates. In a cotyledonary placenta, the chorionic villi are usually restricted to oval or circular patches of
the chorionic sac. Animals having this type
include sheep, goats and cows. Zonary placentas have chorionic villi distributed in an
equatorial band or girdle, although there are
many variations in the distribution of villi.
Discoidal placentas have chorionic villi distributed in a circular plate. Figure 1 has been
simplified and many variations can occur
within each category. For example, the
number of cotyledons may vary from only
a few to well over a hundred depending on
the species, zonary placentas of many carnivores are often not a complete band and
the placenta of the rhesus monkey is usually
bidiscoidal. Additional details can be found
in Amoroso (1952), Steven (1975), Ramsey
(1982) and Mossman (1987).
Classification by composition of the interhemal membrane.— Another scheme for
classifying chorioallantoic placentas is based
on the number and origin of the tissue layers
separating the maternal and fetal blood. This
system, originally formulated by Grosser
(1909, 1927), has been modified as placentas of additional species have been examined, particularly by electron microscopy.
The intervening layers are referred to as the
placental barrier or membrane, or preferably the interhemal membrane (King and
Mossman, 1974). The major placental types
derived from this classification scheme and
their tissue components are shown in Table
1. The different placental types arise as a
consequence of a reduction in the number
of maternal tissue layers. In an epitheliochorial placenta, the maternal uterine epithelium (epithelio) is closely interdigitated
with the vascularized fetal layers (chorion).
Removal of maternal epithelial and connective tissue elements brings about the
apposition of maternal capillary endothelium to the chorion, resulting in an endotheliochorial classification. In a hemochorial
placenta, all intervening maternal layers are
eliminated and maternal blood directly
333
PLACENTAL STRUCTURE AND FUNCTION
TABLE 1. Classification of chorioallantoic placentas by tissues comprising the interhemal membrane.
Type of placenta
Maternal tissue
Endothelium
Connective tissue
Epithelium
Fetal tissue
Trophoblast
Connective tissue
Endothelium
Common examples
Main zoological groups thought to
have the type of placenta indicated
Epitheliochorial
Endotheliochorial
Horse, Pig, Cattle
Perissodactyla
Artiodactyla
Lemuroidea
Cetacea
Pholidota
Cat, Dog
Most Carnivores
Tupaiidae
Bradypodidae
Proboscidea
Tubulidentata
Hemochorial
Human, Rodents, Rabbit
Most Primates
Rodentia
Lagomorpha
Some Chiroptera
Dasypodidae
Hyracoidea
Sirenia
Most Insectivora
Dermoptera
Adapted from Hamilton and Mossman, 1972.
bathes the trophoblast. The "Grosser" system has been criticized for a number of
shortcomings, the most important of which
was the assumption by some early investigators that the number of tissue layers in
the interhemal membrane determines its
thickness and, therefore, from a physiological standpoint, was related to the "efficiency" of placental transfer. As we have
come to know more about active, facilitated
and endocytic transport mechanisms operating in the placenta, we can appreciate that
this is a misleading oversimplification. Also,
more layers do not necessarily mean thicker.
In the epitheliochorial placenta of the pig,
indentation of the uterine epithelium by
maternal capillaries, and indentation of the
trophoblast by fetal capillaries, significantly
reduces the diffusional distance between the
two circulations. Even placentas classified
as hemochorial may have one, two or three
layers of trophoblast (Enders, 1965). An
example of how thinness of the interhemal
membrane alone does not necessarily relate
to maternal-fetal transport is seen in the case
of immunoglobulin transfer to the fetus.
Both the human and guinea pig fetus acquire
their passive immunity during prenatal life
(Brambell, 1970) and each has a chorioallantoic placenta that is hemomonochorial,
i.e., only a single layer of trophoblast sep-
arating maternal blood from fetal capillaries
(Enders, 1965). Yet IgG is transported across
the human placenta, but not that of the
guinea pig. In the case of the guinea pig,
transfer is by way of the yolk sac. In spite
of these cautions, the Grosser system of
classification has retained its usefulness. It
serves as a convenient reminder of the tissue
components that need to be taken into
account when studying morphological,
physiological, endocrinological or immunological functions of the placenta.
PATHWAYS OF MATERNAL-FETAL
EXCHANGE
One of the major functions of the placenta
is obviously to provide for the transfer of
nutrients to support embryonic/fetal growth
and development. Collectively these nutrient materials are sometimes referred to as
embryotroph and are of two general types—
histotroph and hemotroph (Amoroso, 1952).
Histotroph refers to materials derived from
the secretions of uterine glands, material
resulting from the disintegration of maternal tissues and extravasation of maternal
blood. Hemotroph is derived directly from
the maternal blood stream via the placenta.
It is important to bear in mind that physiological transfer of substances from mother
to fetus cannot be accounted for solely by
334
BARRY F. KING
FIG. 2. Diagram illustrating some of the potential pathways of maternal-fetal exchange of substances in a
rodent. (1) A prominent region of exchange is the chorioallantoic placenta, where nutrients may be transferred
from maternal blood to the fetal capillaries of the placenta. In pathway (2a) materials may be transferred from
the edge of the chorioallantoic placenta (and parietal yolk sac) into the uterine lumen; (2b) uterine glandular
secretions enter the uterine lumen; (3) contents of uterine lumen are absorbed by the endoderm cells of the
visceral yolk sac and transferred to capillaries of the vitelline circulation and thence to the fetus; (4) substances
absorbed by the yolk sac may reach the exocelomic cavity (EXO) and cross into the amniotic cavity (AC); (5a)
substances in the amniotic fluid may be absorbed across the embryonic/fetal skin or (5b) may be swallowed by
the fetus and absorbed via the fetal gut. Placental disc modified from Mossman (1987).
transfer from maternal blood to fetal blood
across the chorioallantoic placenta. In many
species, accessory or paraplacental structures function in maternal-fetal exchange.
In others, another type of placenta (most
notably a yolk sac placenta) functions prior
to the establishment of the chorioallantoic
placenta and may function concurrently with
the latter in later gestation. One type of
paraplacental structure that plays an important role in nutrient transfer to the fetus is
the hematoma or hemophagous organ which
occurs in many species. In these regions
extravasations of maternal blood occur and
adjacent phagocytic trophoblast cells ingest
the maternal erythrocytes. Another type of
paraplacental structure is the areolae found
in many ungulates. These are dome-shaped
structures lined by absorptive trophoblast
cells that lie opposite the openings of uterine
glands. The functions of both these paraplacental structures will be considered in
more detail in later sections. A variety of
other types of paraplacental structures also
occurs (Mossman, 1987).
As mentioned above, many species may
have a yolk sac placenta functioning concurrently with a chorioallantoic placenta
throughout much of gestation. This has been
best studied in rodents (see reviews by Brent,
1990;Jollie, 1990; King and Enders, 1991).
Figure 2 illustrates some of the possible
PLACENTAL STRUCTURE AND FUNCTION
routes of maternal-fetal exchange in a
rodent. It is evident that many possibilities
exist. A somewhat similar situation exists
in many primates, including humans, where
the apposition of the chorioamnion with the
uterine wall creates a potential route of
exchange involving passage of substances
into the amniotic fluid where (potentially)
absorption could occur across fetal skin or
gut absorption could occur as a consequence
of fetal swallowing.
MECHANISMS OF MATERNAL-FETAL
IRON TRANSFER
The mechanisms that have evolved in different mammals to provide for iron transfer
to the developing embryo and fetus reveal
a fascinating variety involving both placental and paraplacental structures as well as
hemotrophic and histotrophic sources of the
iron. At least four important mechanisms
have been implicated in the transfer of iron
from mother to fetus.
Absorption of transferrin-bound
iron by the placenta
This mechanism appears to be utilized by
most species with a hemochorial type of
placenta (Seal et ah, 1972; Baker and Morgan, 1973; Morgan, 1980; van Dijk, 1988;
Douglas and King, 1990). It is known that
iron is rapidly transferred to the fetal circulation whereas transferrin is not (Gitlin et
al, 1964; Contractor and Eaton, 1986).
Although a number of steps in the overall
process are unknown, several lines of investigation support the pathway of receptormediated endocytosis illustrated in Figure
3. Transferrin receptors are present on the
apical surface of human syncytiotrophoblast bordering the maternal blood (Wada
et al, 1979; Brown and Johnson, 1981;
Brown et al, 1982). Transferrin binds to the
membrane of microvilli and coated pits on
the trophoblast surface (King, 1976). Transferrin receptors are also present on isolated
human trophoblast cells (Bierings et al,
1988; Douglas and King, 1990). Trophoblast cells in culture internalize transferrin
and transferrin receptors via a system of
coated pits and vesicles (King, 1990). Trophoblast cells in vitro internalize transferrin
by receptor-mediated endocytosis; transferrin is recycled and released back to the
335
medium, whereas iron accumulates intracellularly (Douglas and King, 1990). Iron
accumulates largely in the form of ferritin
although some low molecular weight iron
compounds have also been detected. An iron
regulatory factor and a low molecular weight
iron-binding molecule have been isolated
from human placenta but their precise role
in maternal-fetal iron transfer remains to be
determined (Neupert et al, 1990; Knisely
et al, 1989).
Iron-containing deposits have been
described in the basement membrane area
underlying the trophoblast in human placenta (for references see Salazar and Gonzales-Angulo, 1967). Corresponding electron-dense granules were described by
Salazar and Gonzales-Angulo (1967) who
interpreted them to result from a block to
iron transfer. Hamasaki et al (1985) have
provided conclusive evidence, using x-ray
microprobe analysis, that these basal lamina granules contain iron but referred to the
granules as lipid droplets, a conclusion for
which there is no supporting evidence.
Granules of similar structures were
described in the seal placenta, where they
were interpreted as sites of iron storage
(Sinha and Erickson, 1974). The form in
which iron reaches the fetal circulation
remains an enigma, but once there becomes
associated with fetal transferrin.
Absorption of iron by the yolk sac
This pathway probably is used by a number of mammals, but is best documented in
rodents. The histochemical studies of Wislocki et al. (1946) noted the presence of substantial iron deposits in the rodent yolk sac
as well as endometrial glands. They hypothesized secretion of iron-rich materials from
the glands into the uterine lumen from where
the yolk sac endoderm absorbed the compounds. Subsequent physiological studies
have indicated the yolk sac has at least some
role in maternal-fetal transfer of iron
(Nylander, 1953; Magnusson et al, 1955;
Glasser et al, 1968; Kaufman and Wyllie,
1970; Garrett et al, 1972, 1973). The relative importance of the yolk sac in iron
transfer compared with the chorioallantoic
placenta is the subject of some disagreement
in the above-mentioned studies, perhaps due
in part to variations in gestational age and
336
BARRY F. KING
MATERNAL
BLOOD
D1FERRIC
TRANSFERRIN
\ y TRANSFERRIN
I RECEPTOR
*
IRON
( 3 APOTRANSFERRIN
FERR1T1N
FIG. 3. Diagram illustrating some of the cellular pathways involved in the absorption of maternal transferrinbound iron by trophoblast of a hemochorial placenta such as the human. CURL, Compartment of uncoupling
of receptor and ligand.
to the form in which iron was administered.
In the rat, Garrett et al. (1972,1973) showed
the yolk sac had a significant role in iron
transport during certain days of gestation
and that yolk sac tissue had the capacity to
take up iron from FeCl3 and from serum
(transferrin). The observation by Garrett et
al. (1972) that it was the "circumferential"
portion of the yolk sac that was particularly
important in iron uptake is intriguing. This
could mean that the area was important
because the yolk sac is highly villous in that
region or it might mean that the "endodermal sinuses" on the surface of the chorioallantoic placenta are contributing to transport by this pathway, as has been suggested
for calcium transport (Bruns et al., 1985).
Recent studies have indicated that transferrin can be transported by rat yolk sac
(McArdle and Priscott, 1984; Huxham and
Beck, 1985; Thiriot-Hebert, 1987). This
appears to occur via receptor-mediated
endocytosis, and may occur early in gesta-
tion, before the establishment of the chorioallantoic placenta. As gestation proceeds,
the yolk sac decreases in importance and
the transport system of the chorioallantoic
placenta rapidly matures (McArdle and
Morgan, 1982). Electron-dense, iron-containing granules have been observed in the
basement membrane of a rodent yolk sac
(King and Tibbitts, 1976). These are virtually identical to those described in human
placenta and may represent sites of temporary iron storage.
The yolk sac of the shrew Blarina also is
involved in iron transport to the fetus, but
in this case an unusual situation exists
wherein a portion of the yolk sac becomes
a hemophagous area involved in erythrophagocytosis (Wimsatt and Wislocki, 1947;
King et al., 1978); in most other mammals,
the fetal component of the hemophagous
region is the chorioallantoic membrane, not
the yolk sac (see next section). In the shrew,
a specialized region of trophoblast is
PLACENTAL STRUCTURE AND FUNCTION
337
TROPH
FIG. 4(A). Diagram of the histological arrangements at the marginal hemophagous region of a carnivore placenta
(e.g., cat). Maternal erythrocytes are extravasated from endometrial vessels (MC) into the uterine lumen (UL).
Trophoblast cells of the chorion (TROPH) in this region phagocytose maternal erythrocytes and transfer maternal
iron to fetal capillaries (FC). UE, uterine epithelium; UG, uterine gland. (Redrawn and adapted from Mossman,
1987.)
involved in localized disruption of endometrial blood vessels and maternal blood is
extravasated into the uterine lumen. Phagocytic trophoblast cells ingest and degrade
maternal red cells, and iron-containing
compounds are transferred to the yolk sac
cavity. From here visceral yolk sac endoderm cells absorb the iron-rich components
and store them as iron pigments. The storage of pigments is sufficiently great so as to
impart a distinctly green color to the endoderm cells. By mechanisms unknown the
iron is mobilized and transferred to other
fetal tissues.
Phagocytosis of maternal erythrocytes
In a number of species, localized extravasations of maternal blood occur opposite
regions of specialized chorion with phagocytic trophoblast cells. These accessory or
paraplacental regions are known as placental hematomas, hemophagous organs (Creed
and Biggers, 1964) or hemophagous regions
of the placenta (Burton, 1982). Hemophagous regions occur in many carnivores,
insectivores, bats and ungulates and vary
greatly in location and morphology (see
Wimsatt, 1962; Steven, 1975; Ramsey,
1982; Mossman, 1987). Blood from endometrial vessels is extravasated into a space
(typically the uterine cavity) (Fig. 4A). The
manner in which the uterine vessels are rendered leaky is poorly understood although
in a few cases it appears to be due to the
invasive activity of trophoblast (King et ai,
1978; Leiser and Enders, 1980). Blood which
has accumulated is phagocytosed by chorionic trophoblast cells. Indeed, pigments
arising from the degradation of hemoglobin
results in coloration of the hemophagous
regions. Thus, the marginal hematoma of
the dog is referred to as the "green border,"
that of the cat the "brown border" and is
reddish-brown in some bears (see Burton,
338
BARRY F. KING
FIG. 4(B). Diagram of some of the proposed pathways of iron transfer by choricnic trophoblast cells (TROPH)
of a hemophagous region. Maternal erythrocytes in the uterine lumen (UL) are engulfed and reside in erythrophagosomes (EP). Various stages of degeneration occur in erythrolysosomes (EL). Iron (Fe) may be released
from hemoglobin-containing lysosomes (HLy) and stored as cytoplasmic ferritin (FeFt). The manner in which
the iron exits the trophoblast, crosses the basal lamina (BL), and enters the fetal capillary (FC) is unknown.
Within the capillary iron is presumably associated with fetal transferrin (FeTf). (Redrawn and adapted from
Burton et ai, 1976 and Burton, 1982.)
1982). While it is generally accepted that,
in species with prominent hemophagous
regions, fetal iron stores are derived from
breakdown of maternal erythrocyte hemoglobin, there are very few studies directly
addressing this issue. Seal et al. (1972), citing unpublished experiments, used 59Fehemoglobin-labelled erythrocytes to dem-
onstrate that label could subsequently be
localized in the hemophagous region of the
racoon placenta and also in fetal hemoglobin.
Ultrastructural studies of the hemophagous regions and of the process of erythrophagocytosis have been carried out in a
number of species including sheep (Myag-
PLACENTAL STRUCTURE AND FUNCTION
kaya and Vreeling-Sindelarova, 1976; Burton et al, 1976), seal (Sinha and Erickson,
1974), shrew (King et al, 1978), cat (Malassine, 1977, 1982; Leiser and Enders, 1980),
dog (Burton, 1982) and ferret (Gulamhusein
and Beck, 1975). The sequence involved in
erythrophagocytosis seems similar in most
species thus far examined (Fig. 4B). Microvilli or cellular processes of the trophoblast
cells partially engulf whole or fragmented
erythrocytes. Erythrophagosomes and erythrolysosomes are formed in the apical
cytoplasm and degradation occurs. Subsequent metabolic pathways of iron in these
trophoblast cells are not well understood.
Hemoglobin-containing lysosomes may be
the main sites of hemoglobin degradation
and iron may be stored in the cytoplasm in
the form of ferritin or hemosiderin (Burton,
1982; Malassine, 1982). How iron is eventually delivered to the fetal circulation is
unknown, but within the fetal capillary iron
is presumably associated with transferrin
(Burton, 1982). In addition to questions
remaining about the detailed pathway of iron
transport, it is unclear whether this hemoglobin-derived iron is sufficient to meet all
of the fetal requirement in these species,
particularly in late gestation.
Absorption of iron-containing
uterine secretions
In a number of species that do not have
a hemochorial placenta, transferrin-bound
iron has a low rate of transfer to the fetus,
too low to account for most of the iron the
fetus accumulates (Seal et al, 1972). Some
of these species also lack hemophagous
regions, leading to the suggestion that other
paraplacental structures must be participating in maternal-fetal transfer of iron. In
the case of the pig, evidence points to the
areolae as important sites of iron transfer
derived from uterine secretions (histotroph). As mentioned earlier, areolae are
specializations of the chorion located opposite the mouths of uterine glands (Fig. 5)
and have long been suspected as sites of
nutrient transfer (Brambel, 1933; Friess et
ah, 1981). Wislocki and Dempsey (1946)
demonstrated the presence of non-heme iron
in pig uterine glands, secretions and areolae,
and called attention to the potential impor-
339
tance of the glands and areolae as a pathway
for nutrient transfer. Direct experimental
evidence implicating the areolae in iron
transport to the fetus was provided by Palludan et al. (1970). They administered 59Fe
to the mother and found that the labelled
iron accumulated in the uterine glands and
secretions and over the areolae. Furthermore, the iron was transported to the fetus
in a non-dialyzable (presumably proteinbound) form.
More recently, the composition of pig
uterine secretions has been actively investigated (Roberts et al, 1986; Roberts and
Bazer, 1988). One major component of porcine uterine secretions is a glycoprotein acid
phosphatase that contains bound iron.
Because of the evidence implicating this glycoprotein in transplacental iron transport it
has been called uteroferrin (Roberts and
Bazer, 1980). Uteroferrin is synthesized and
secreted by the uterine gland epithelial cells.
Specialized trophoblast cells lining the areolae absorb uteroferrin from the areolar
lumen by an endocytic pathway (Chen et
al., 1975; Renegar et al., 1982; Raub et al.,
1985). Uteroferrin is transported intact from
the trophoblast cells to the fetal circulation
although the precise pathways involved have
not been delineated (Renegar et al., 1982).
Uteroferrin is distributed to fetal organs,
including spleen and liver, and its iron is
incorporated into fetal hemoglobin (Buhi et
al., 1982). Excess uteroferrin is cleared by
the fetal kidneys and enters the allantoic sac
wherein additional metabolism occurs,
including the transfer of its iron to transferrin (Buhi et al., 1983; Renegar et al.,
1982).
At least for the greater part of gestation,
uteroferrin is secreted and absorbed in sufficient quantities to provide for the iron
requirements of the developing fetus.
Whether it is sufficient during later gestation, or whether other mechanisms are
invoked, remains to be demonstrated. The
above evidence provides a strong case for
the involvement of paraplacental structures
(areolae) and uterine secretions (histotroph)
as an important mechanism of iron transport in the pig. To what extent this pathway
is used in other species is largely unknown,
although uteroferrin-like proteins have been
340
BARRY F. KING
FIG. 5. Diagram of the general arrangements of tissues in the region of an areola of the pig placenta. Epithelial
cells of the uterine glands (UG) secrete iron-rich compounds (#) such as uteroferrin into the uterine lumen (UL)
and areolar space. Absorptive trophoblast cells (TROPH) of the areolar lining endocytose the secretions and
transport them to underlying fetal capillaries (FC). MC, maternal capillaries. (Redrawn and modified from
Mossman, 1987.)
found in the horse (McDowell et ai, 1982,
1990). Also, I have postulated that a similar
pathway may be used for iron transport in
a primitive primate (Galago) that has an
epitheliochorial placenta and paraplacental
specializations (chorionic vesicles) similar
in structure to areolae (King, 1984). This
postulate was based not only on the many
structural similarities but also on the histochemical observation that iron is present
in the uterine glands and chorionic vesicles
in Galago (Butler and Adam, 1964). Thus,
iron transfer by this mechanism may be
more common than currently appreciated.
ACKNOWLEDGMENTS
The author's original investigations
reported herein were supported by National
Institutes of Health grants HD 11658 and
RR00169. I thank Grete Fry for technical
assistance, Carrie Beth Mattos for rendering the drawings, Dr. A. C. Enders and
Sandy Enders for reading the manuscript,
and Clarrise Northern for typing the manuscript.
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