Vol. 12, No. 2
97
REVIEW
The rat as an animal model for
fetoplacental development: a reappraisal
of the post-implantation period
Bruno M. Fonseca, Georgina Correia-da-Silva, Natércia A. Teixeira1
Laboratory of Biochemistry, Department of Biological Sciences, Faculty
of Pharmacy, University of Porto and Institute for Molecular and Cell
Biology (IBMC), Porto, Portugal
Received: 5 August 2011; accepted: 25 March 2012
SUMMARY
Following implantation in rodents, the uterine stromal fibroblasts differentiate
into densely packed decidual cells. This process, called decidualization, is wellorchestrated and progresses both antimesometrially and mesometrially, creating
two regions with distinctive cellular morphologies. In addition, subsequent
placental development is dependent on the invasion of the trophoblast, the process
intimately linked to the endometrial tissue remodelling and depending largely
on the environment created by the decidua; this phenomenon is crucial for
the establishment and maintenance of pregnancy. The key mechanisms
underlying the maternal tissue remodelling and trophoblast invasion remain
poorly understood. The rat, just like human beings, exhibits a highly invasive
type of placental development, the haemochorial placentation. For obvious
ethical reasons, the studies of endometrial tissue remodelling throughout
1
Corresponding author: Faculdade de Farmácia da Universidade do Porto - Laboratório de Bioquímica Rua de Jorge Viterbo Ferreira No 228, 4050–313 Porto, Portugal; e-mail: [email protected]
Copyright © 2012 by the Society for Biology of Reproduction
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Feto-placental development in rats
pregnancy in humans are greatly limited. Although the rat differs somewhat
from humans with regards to the implantation process, it is an appropriate
model for studying the mechanisms of decidualization as well as subsequent
remodelling of the uterine tissues and fetoplacental development. As
decidual remodelling is very closely linked to placentation and the maternalfetal interactions in the rat show several important similarities to human
placentation, the morphological alterations occurring during the postimplantation period in the rat have been addressed in the present review.
Reproductive Biology 2012 12 2: 97–118.
INTRODUCTION
At implantation, the uterus is receptive to blastocysts (“window of implantation”) and is under the influence of ovarian steroid hormones. In mice
and rats, implantation occurs between days 4 and 5 of pregnancy, considering
the first day of pregnancy as the day on which a vaginal plug (mouse) or
spermatozoa (rat) are present in the vagina [50, 65]. Following implantation,
the endometrial fibroblast-like stromal cells proliferate and differentiate
into decidual cells. In women, decidualization occurs spontaneously
during the late secretory phase of the menstrual cycle, while in rodents
decidualization occurs in response to implantation or an artificial stimulus;
in the latter case, it gives rise to the deciduoma.
The morphology of the decidua changes with the advancement
of gestation. Initially, it develops in the antimesometrial pole of the uterine
lumen, forming the antimesometrial decidua. After the attainment
of full development, it regresses to give room for the growing conceptus.
Concomitantly with the regression of the antimesometrial decidua,
the stromal cells from the mesometrium begin to differentiate into
decidual cells to form the mesometrial decidua. The latter provides an
affable environment for placental growth and degenerates concurrently
with the invasion of trophoblast cells, supporting the establishment
of the placental bed. In the present review we describe the remodelling
of rat uterine tissues during gestation. We present detailed information
Fonseca et al
99
Figure 1. The timeline of main events during the rat gestation. After fertilization,
the sequence of events is similar among different rodent species. In response
to implantation, which occurs around day 5 in rats, the antimesometrial decidua
develops and subsequently regresses by day 12 (decidua capsularis). The mesometrial decidua develops concurrently with trophoblast invasion to initially form
the choriovitelline placenta, which gives rise to the definitive placenta.
on the maternal-fetal interactions with the special emphasis on decidual
establishment and regression. Moreover, as trophoblast invasion in the rat
proceeds along two different pathways, interstitial and endovascular, we
will describe this phenomenon, which shares a number of similarities with
human trophoblast invasion. Figure 1 depicts the main events during rat
gestation and times at which they occur.
Spatio-temporal characterization of rat antimesometrial decidua
Successful establishment of pregnancy is dependent upon the proper growth
and development of the uterine endometrium for blastocyst implantation.
The uterus must be hormonally prepared and then a stimulus, normally
provided by the embryo, triggers the process of decidualization. Stromal
fibroblasts in the endometrium proliferate and differentiate into decidual
cells, which involves characteristic changes in cell morphology [1]. Although
the molecular mechanisms associated with decidualization remain poorly
understood, numerous factors have been implicated in the regulation of this
process. Among these are ovarian hormones and other locally synthesized
molecules such as interleukin 11 (IL-11; [8]), relaxin [32], prostaglandin
E2 (PGE2; [42]), leukemia-inhibitory factor (LIF; [67]), and activin A [82].
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Feto-placental development in rats
In addition, recent evidence suggests that decidual cells are important
players in the recognition of implanting “competent” embryos [7, 70].
Although the embryonic factors BMP2, WNT have been suggested to act on
the decidual cells and the JAK/STAT and cAMP dependent pathways have
been reported to be activated in these cells, the exact mechanisms involved
remains unknown [30, 46, 85].
Following the attachment of the blastocyst, apoptosis of the luminal
epithelial cells and decidual cell reaction at the site of implantation occur.
During the initial stages of hatched blastocyst invasion, trophoblast cells
erode the uterine epithelial cells, leaving the basement membrane temporarily
intact [77]. Once stimulated, the stromal fibroblasts from the subepithelial
antimesometrium zone undergo differentiation, giving rise to the primary
decidual zone [24]. Primary decidual cells are large, with basophilic cytoplasm,
two or more nuclei, and abundant endoplasmic reticulum, mitochondria,
lysosomes and well-developed Golgi complexes [56]. These cells express
alkaline phosphatase [29] and their appearance is associated with a significant
increase in DNA, RNA and protein content indicating high decidual growth
dynamics [6]. Concomitant with the appearance of the primary decidual zone,
the surrounding stromal cells undergo mitosis heralding the differentiation into
antimesometrial decidual cells, which results in the formation of the secondary
decidual zone. By day 8 of gestation, decidualization spreads out to the basal
region of the endometrium adjacent to the muscular layer (fig. 2; [77]).
The formation of decidua involves a tight equilibrium between
decidual cell proliferation and death, which is crucial for the maintenance
of pregnancy. In vivo studies demonstrated that proliferation was intense
in the first period of decidual cell reaction but it declined at the later stages
[15]. In fact, the antimesometrial decidua reaches its maximum development
on day 10 of pregnancy (fig. 2). By day 12, the regression of decidua
is complete and it forms the decidua capsularis (fig. 2; [11]). Degradation
of the antimesometrial decidua occurs primarily by programmed
cell death, as previously demonstrated by immunoreactive caspase-3
and TUNEL positive staining detected as early as day 8 of pregnancy [15].
However, the markers of necrosis were also detected during the regression
of the antimesometrial decidua. It was suggested that apoptosis is followed
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Figure 2. An illustration of rat uterine tissue architecture from days 8 to 12 of pregnancy. The blastocyst implants on the antimesometrial side of the uterus and decidual
cells develop to form the primary decidual cell zone. On day 8, the antimesometrial
decidua (AMD) forms and on day 10, AMD is fully developed and decidualization
is occurring in the mesometrium (MD). By day 12, trophoblast cells of the ectoplacental
cone (the primordial placenta) have started to penetrate into the mesometrial decidua.
By this time, the antimesometrium has completely regressed, being now referred to as
decidua capsularis (DC), and the mesometrial triangle can now be observed.
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Feto-placental development in rats
by secondary necrosis, which triggers the release of cellular constituents
activating the inflammatory processes [15]. Using the pseudopregnancy
model, Tessier et al reported the expression of active caspase-3 in the decidua
only after day 10, suggesting that the presence of the conceptus may
accelerate the initiation of apoptosis in this tissue [81].
On day 9 of gestation, the fibrinoid capsule, a structure of condensed
tissue, appears externally to the antimesometrial decidua (fig. 2).
Between the fibrinoid capsule and the innermost smooth muscle layer
of the uterus, there is a thin layer of non-decidualized stroma containing
sporadic endometrial glands, which secrete various substances required
for survival and development of the conceptus [35]. Although the precise
role of the endometrial glands during pregnancy is not known, they appear
to be required both during the peri-implantation period and placental
development [5]. At the time of the fibrinoid capsule formation, endothelial
cells in the lateral wings of the decidua proliferate rapidly, which results
in the formation of large venous sinusoids. These endothelial cells are
in intimate contact with decidual cells to facilitate the transfer of nutrients
from the decidua to adjacent blood vessels [28]. This region, between
the lateral sinusoids and antimesometrial decidua, contains the cells with
high glycogenic content and is commonly known as the lateral decidua or
the glycogenic wing area (fig. 2; [76]).
Rat mesometrial decidua: remodelling of uterine tissues during
fetoplacental development
Mesometrial decidual cells appear in the central region of the endometrium
few days after antimesometrial decidual cell reaction as a result of the differentiation of cells from the mesometrial pole. These cells are smaller than
those in the antimesometrial decidua, irregular in shape, and they contain
a single nucleus. By day 12 of gestation, the mesometrial decidua is fully
differentiated. With time, there is an enlargement of adjacent blood vessels
and the central zone of the mesometrial decidua is invaded by the trophoblast
cells of the ectoplacental cone, resulting in the formation of the definitive
placenta by day 14 (fig. 3). From days 14 to 16, the decidua undergoes apoptotic
Fonseca et al
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regression [15]. By day 19, it is confined to a marginal uterine region, forming
the maternal component of placenta-the decidua basalis (fig. 3). In fact,
the degeneration and disappearance of both antimesometrial and mesometrial
decidua is a unique feature of rat placentation.
During the process of decidualization, a set of specialized leukocytes,
the uterine natural killer (uNK) cells, populate the decidua. These
leukocytes are phenotypically and functionally different from peripheral
NK cells. Although the exact mechanisms involved in the recruitment
of uNK to the decidua during pregnancy are still unknown, it seems
to be hormonally-controlled and involves IL-15 [84]. Moreover, as
demonstrated in the deciduoma model, the colonization of the decidua
by uNK cells seems to be independent of the presence of the implanting
embryo [38, 54, 58]. It is, however, well documented that the conceptus plays
a critical role in regulating the number and function of uterine uNK cells
during decidualization [38]. With the progression of pregnancy, uNK cells
become more abundant and acquire a granular phenotype. The characteristic
membrane-bound granules contain perforin and granzyme B, which
control the trophoblast invasion and maternal vascular remodelling [13,
45, 55]. After day 15 of pregnancy, uNK cells undergo degranulation
and their number decreases as a result of an active process of programmed
cell death [33]. By day 12, uNK cells are also present in the mesometrial
triangle, a zone between the circular and longitudinal uterine muscle layers.
Often referred to as the “metrial gland” (an obsolete term), this region
enlarges with the progression of pregnancy and appears to be an extension
of the mesometrial decidua [19, 20]. The mesometrial triangle also comprises
the entry point for blood vessels, supplying both the placenta and fetus.
Besides numerous uNK cells clustered around the vessels, the metrial gland
also contains the endometrial stromal and trophoblast cells.
It is apparent that decidualization involves a temporal and spatially
co-ordinated sequence of events with the differentiation of various cell
types occurring in different regions of the gravid uterus and at different
times. The antimesometrial decidua has characteristics of an endocrine
organ, secreting a variety of hormones and growth factors such as decidual
prolactin-like hormones, follistatin, activin and transforming growth
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Feto-placental development in rats
factors [36]. On the other hand, the mesometrial decidual tissue secretes
high levels of α2-macroglobulin (α2-MG; [79]). This glycoprotein has
the ability to inhibit all types of proteases and bind numerous cytokines
and growth factors. In addition, the mesometrial decidua also secretes
other factors such as insulin-like growth factors (IGFs; [14, 21]) and IL-6
[23]. The progressive decidualization of the mesometrial stroma prepares
the uterine lining for the presence of the invasive trophoblast. In fact,
the temporal and spatial patterns of mesometrial decidua regression are
closely associated with the pattern of trophoblast invasion and the resulting
vascular remodelling.
Placental development in the rat
The placenta is a specialized pregnancy-specific structure that develops
concurrently with the embryo and is composed of numerous cell types.
Among these are the trophoblast cells, the earliest extra-embryonic cells
to differentiate from the mammalian embryonic cells. Although the general
structure of the placenta varies considerably among mammalian species,
the basic morphology, main cell types and functions as well as the molecular
mechanisms underlying placental development are conserved across species
[47]. In contrast, the specific hormones governing the maternal recognition
of pregnancy are different. The trophoblast in humans and other primates
produces a chorionic gonadotropin that directly stimulates the secretion
of luteal progesterone, whereas the placenta in rodents produces lactogens [31].
The trophoblast cells play a primary role in protecting the embryo
from noxious deleterious substances, programming the maternal support
and preventing the maternal immune rejection. They also ensure an
appropriate bidirectional nutrient/waste flow required for normal growth
and maturation of the embryo. Thus, through creating the milieu in which
the embryo and fetus develop, placentation is fundamental for assuring
successful pregnancy and it also impinges on the postnatal health status.
Although several studies attempted to corroborate the molecular pathways
underlying the development of the placenta, our current knowledge is mainly
based on mouse studies involving transgenic animals exhibiting the defects
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Figure 3. Rat implantation unit during fetoplacental development. On day 14,
the placenta is fully developed and decidual regression is apparent in both the mesometrial and antimesometrial decidua. The metrial gland, or mesometrial triangle,
appears as an extension of the mesometrial decidua. By the end of pregnancy,
and particularly on day 19, just a layer of few decidual cells remains to give space
for placental growth.
in placental development [4, 17, 26, 69]. Several genes were identified as
critical for normal placental development and function. These include
the genes for cystatin C [3], cathepsins [71], plasminogen activator inhibitor
type 1 (PAI-1) and 2 (PAI-2; [27]), and α2-MG [25].
The haemochorial placentation is the most invasive form of placentation,
with the penetration of trophoblast cells into the uterine compartment where
they establish direct contact with maternal vasculature and with extensive
remodelling of the spiral arteries. The blood vessels lose their elastic lamina
and smooth muscle layer, and consequently the responsiveness to circulating
vasoactive compounds [61, 62]. This type of placentation occurs in humans
and most rodents. Various studies of the depth of trophoblast invasion
Figure 4. Schematic representation of rat chorioallantoic placenta. A schematic of the basic structures comprising the implantation unit in mid-pregnancy: myometrium, metrial gland, decidua and placenta. Note the trophoblast lineages and their
location within two distinct structures of the placenta: the basal (giant trophoblast cells, spongiotrophoblast cells and glycogenic cells) and the labyrinth zone (giant trophoblast cells and syncytiotrophoblast cells).
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Feto-placental development in rats
Fonseca et al
107
during placentation in mice revealed significant differences when
compared to the rat. In fact, in the rat both endovascular and interstitial
trophoblast invasion are observed. In the mouse, trophoblast invasion into
the maternal spiral arteries is limited to the decidual compartment [2, 49]
and the interstitial invasion does not reach the mesometrial triangle [64].
Considering those differences, the rat is the most appropriate rodent model
for the studies of extensive myometrial invasion as seen in humans [62].
Moreover, histological studies revealed important similarities between rats
and humans with regards to remodelling of the spiral arteries [9, 83].
Although the placental development in the rat starts immediately after
the attachment of the blastocyst to the uterine epithelium, the definitive
placenta develops from the ectoplacental cone. Therefore, the two placental
structures can be distinguished: the choriovitelline and chorioallantoic
placenta [75]. The choriovitelline placenta is transitory, being physiologically
significant between implantation and mid-gestation, and is comprised
of a single differentiated trophoblast cell type, the giant trophoblast
cells. The chorioallantoic placenta represents the definitive placenta
and is comprised of four differentiated trophoblast cell phenotypes, namely
the trophoblast giant cells, spongiotrophoblast cells, glycogenic trophoblast
cells, and syncytiotrophoblast cells (fig. 4; tab. 1). Two morphologically
and functionally distinctive placental regions, the basal and labyrinth
zones, can be seen in the chorioallantoic placenta [74]. The basal zone,
also known as the junctional zone, is located between the uterine decidual
tissue and the labyrinth zone. It contains giant trophoblast cells, localized
at the maternal-placental interface, spongiotrophoblast and glycogenic
trophoblast cells. The labyrinth zone is positioned at the fetal interface,
being comprised by giant trophoblast cells, syncytiotrophoblast cells, fetal
mesenchymal cells and vasculature.
The majority of cell lineage studies have been carried out using
mouse placenta, although there is sufficient evidence to suggest that
the origin of placental cells in mice is similar to that in the rat [73].
All trophoblast cell subtypes differentiate from the trophectoderm
layer of the blastocyst; however, they can be distinguished on the basis
of their morphology, intraplacental location, and the pattern of gene
Spongiotrophoblast
Syncytiotrophoblast
Invasion of decidua
[18]
Immunological,
endocrine
and structural
functions [40]
Present only
in the labyrinth zone
- fetal interface [57]
Nutrient transport
[72]
Unknown
Invasion of decidua
[86]
Expands to decidua
but also into spiral
arteries [2, 86]
Invasiveness
Invasive
and endocrine
functions
[37]
Functions
Present only
Energy reservoir [22]
in the basal zone [57]
Present only
in the basal zone [57]
Derived from
the ectoplacental
cone [10]
Giant trophoblast
Derived from
the ectoplacental
cone [10]
Fusion
of cytotrophoblast
cells [16]
The choriovitelline
placenta
and in both zones
of the chorioallantoic
placenta [57]
Derived from
the ectoplacental
cone;
endoreduplication
[10, 51]
Glycogenic trophoblast
Location
Differentiation
Cell type
Table 1. Main features of various types of differentiated rat trophoblast cells
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Feto-placental development in rats
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109
expression [48, 66, 68]. The term “giant trophoblast cells” derives from
their enormous size, which is a consequence of genome amplification.
The trophoblast cells undergoing differentiation into the giant cells exit
the proliferative cell cycle and enter a genome-amplifying endocycle, also
known as endoreduplication [39]. The giant trophoblast cells are analogous
to human extravillous cytotrophoblast cells and exhibit characteristic
invasive activity. In addition, these cells are the most important
endocrine cells of the placenta that promote both local and systemic
physiological adaptations in pregnancy [75]. Because of the difference
in time of trophoblast cell differentiation, the giant trophoblast cells are
referred to as the “primary” or “secondary” cells in the choriovitelline
and chorioallantoic placenta, respectively. While the primary giant cells are
formed from the trophectoderm layer of the blastocyst during implantation,
the secondary giant cells arise after implantation around the margins
of the ectoplacental cone [18, 37]. The spongiotrophoblast cells exhibit
important endocrine functions and, as they are situated immediately
beneath the giant trophoblast cells, they may also support the development
of the labyrinth zone [18]. The placenta accumulates glycogen, and this
is most marked in rodents, in cells called the glycogenic trophoblast cells.
They are embedded in the spongiotrophoblast and are considered a potential
energy reservoir [22]. The spongiotrophoblast cells and glycogenic
trophoblast cells originate from the same placental structure as the giant
trophoblast cells, the ectoplacental cone [10]. The syncytiotrophoblast
cells are multinucleated and are formed by the fusion of the trophoblast
progenitor cells, the cytotrophoblast cells. They have been implicated in bidirectional transport of nutrients and waste between maternal and fetal
compartments [72].
Prior to placentation, the outer cells of the blastocyst (trophoectoderm)
breach the uterine epithelium and penetrate the basement membrane
and underlying connective tissue. Subsequently, a more intense invasion
occurs, involving both vascular and endometrial remodelling. Endovascular
invasion is the expansion of trophoblast cells into the spiral artery located
in the uterine decidua. Endovascular trophoblast cells replace endothelial
cells and appear as a collar of only a few cells in thickness surrounding
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Feto-placental development in rats
the vessel [9]. The interstitial trophoblast invasion spans the penetration
of trophoblast cells through the uterine stroma up to the metrial gland [59].
In the rat, the interstitial trophoblast invasion is similar to that in humans
in that it extends beyond the decidua during the last third of gestation [12, 83].
Trophoblast invasion in mice is more limited and almost entirely confined
to the uterine mesometrial decidua [4, 12, 60]. The trafficking of trophoblast
cells from the chorioallantoic placenta into maternal tissues is well defined.
Interstitial invasion follows vascular invasion. On day 16 of gestation,
interstitial invasion is already significantly advanced and it continues
throughout pregnancy beyond the decidua, resulting in the colonization
of the mesometrial triangle by the end of pregnancy [4, 83].
It has been suggested that uNK cells are directly involved in the migration
of trophoblast cells into the uterine stroma and/or myometrium [4]. In fact,
the invading trophoblast cells occupy the locations previously occupied
by uNK cells, indicating a regulatory role for uNK cells in trophoblast
invasion. This hypothesis is further supported by the defects in mesometrial
blood vessel remodelling and an alteration in the timing of trophoblast cell
invasion observed in uNK deficient mice [12]. Successful pregnancy requires
the balance between all the factors involved. Synchronization between
uNKs, invasive trophoblast cells and decidual cells is crucial to produce
a suitable environment to ensure immune tolerance and sufficient vascular
and decidual remodelling throughout pregnancy in order to establish an
adequate nutrient transfer to the growing embryo.
Abnormal placentation and its consequences for human pregnancy
In mammals, the placenta is an essential interface between the maternal
and the fetal circulation formed to carry O2-rich blood and nutrients
to the developing fetus. It is now clear that a disturbance of the invasion
of trophoblast cells (fetal origin) into the uterine tissues (maternal tissues)
can result in various clinical problems. Thus, it is important to elucidate
the underlying mechanisms of these processes in normal pregnancy
using, for ethical reasons, an animal model. In addition to the same type
of placentation, an animal model should have a deep trophoblast invasion
Fonseca et al
111
comparable to that in humans. The non-human primates with a deep
trophoblast invasion are the chimpanzee and gorilla that cannot be used
as experimental animals, whereas the rhesus monkey and baboon exhibit
a lesser interstitial invasion with only restricted endovascular invasion
into the decidua [23, 63]. The rodents posses haemochorial placentae, and,
in the case of the rat, a deep trophoblast invasion occurs with remodelling
steps of the spiral artery that are similar to those in humans [80]. However,
due mainly to the lower number of spiral arteries, the rat is not a good model
to study placentation disorders in humans.
The invasion of the trophoblast transforms uterine spiral arteries into
open and straight vessels, resulting in a dramatic decline in the uterine arterial
resistance. However, as a result of excessive restraint of trophoblast cells
by the decidua, an inadequate trophoblast invasion into arteries and uterine
wall can occur leading to deficient blood supply and consequently lower levels
of O2 delivered to the developing fetus. The main problems stemming from
the inefficient blood supply are fetal prematurity, fetal growth restriction
and preeclampsia [34, 41]. For example, during the preeclamptic pregnancy,
trophoblast invasion into maternal tissues is abnormally shallow and uterine
spiral artery remodelling is incomplete. Normally, the programmed cell death
occurs in maternal tissues in order to facilitate trophoblast access to maternal
vessels. However, this activity is markedly reduced during preeclampsia
resulting in the formation of an arteriolar system with high resistance
[52, 53]. On the other hand, it is also extremely dangerous if an excessive
penetration of the uterine wall by trophoblast cells occurs as a result of an
absent or deficient decidua. An overly extensive trophoblast invasion results
in the placenta creta, which is a cause of a massive postpartum haemorrhage
and commonly leads to emergency hysterectomy [44]; without medical
intervention, this condition frequently results in maternal death from
haemorrhage. The exact pathogenesis of the placenta creta is unknown
but it has been suggested to result from a primary deficiency of decidua,
abnormal maternal vascular remodelling, excessive trophoblast invasion, or
a combination of these factors [43, 78]. Although the primary cause of some
miscarriages cannot be clearly defined, the understanding of all mechanisms
involved in the uterine-trophoblast cross-talk is crucial. Any factor disrupting
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Feto-placental development in rats
the balance in the interactions between trophoblast and uterine tissue can
have a deleterious effect on gestation.
GENERAL DISCUSSION
Pregnancy involves complex alterations in the structure and function
of the uterus both before and after implantation. Decidualization constitutes
the primary process responsible for uterine remodelling during pregnancy,
though the specific functions of the decidual cells are still an intriguing
and unresolved issue. The rat, due to its superficial implantation, is not an
appropriate animal model to study this process, but it is a good model for
studying the mechanisms of decidualization and remodelling of the uterine
spiral arteries in humans. The main difference between rodent and human
decidualization is that the process starts spontaneously in humans, whereas
in rodents decidualization occurs only in response to the blastocyst or
an artificial stimulus; the latter ultimately results in the deciduoma. As
pregnancy progresses, decidual tissue regresses and, concomitantly,
the formation of the placenta and invasion of trophoblast cells into maternal
tissues occur. In comparison to primates, rodents have a shorter gestation
period with a fully functional placenta present for only one week and a low
number of spiral arteries. In spite of these differences, rodent species
resemble humans in that they exhibit haemochorial placentation and,
in the case of rats, a pronounced decidual cell reaction and trophoblast
invasion, which require a strict interaction between the maternal blood
vessels and placenta [1, 9, 60].
The mouse is a frequently used species for either decidua or fetoplacental
development studies, mainly because of numerous advancements
in the gene-targeting technology. However, in contrast to humans and rats,
the mouse uNK cells seem to be more important for arterial remodelling than
trophoblast cells. In addition, the interstitial invasion in mice is not as deep
as in the rat. Trophoblast invasion in the rat proceeds along two different
pathways, interstitial and endovascular [9, 83], similar to human beings.
Moreover, the depth of endovascular trophoblast invasion and vascular
Fonseca et al
113
remodelling of spiral arteries in the rat are similar to those in humans [9,
60]. Therefore, the rat constitutes a good experimental model for the studies
of trophoblast invasion, which is intimately associated with the remodelling
of maternal tissues during the normally progressing pregnancy. However,
as mentioned above, it is not an appropriate model to study human
pregnancy disorders. Lastly, the environment created by decidua is crucial
for the maintenance of pregnancy and it pre-determines the extension
of trophoblast invasion observed in both rats and humans. Hence,
the abnormalities in either the establishment or remodelling of decidual
tissue may have a negative impact on normal gestation and are commonly
associated with some pregnancy-related pathological conditions such as
preeclampsia or spontaneous abortions.
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