LECTURE 7: EXTRA-EMBRYONIC MEMBRANES AND THE

PLACENTA: REGULATION OF THE FETAL MILIEU

Reading Assignment: Moore pp 119-196.

A. PLACENTAL DEVELOPMENT AND STRUCTURE

1. The extra-embryonic trophoblast-derived tissue serves three

functions.

a) The trophoblast plays an important role in implantation of the

blastocyst into the uterine endometrium.

b) After vascularization, the forming placenta aids in the transport of

soluble substance between fetus and mother. The placental "barrier" is not really
a barrier. There is abundant evidence that a great variety of substances cross
from maternal to fetal blood.

c) The syncytiotrophoblast has a regulatory function in producing

hormones that are essential for fetal development.

B. DEVELOPMENT OF THE PLACENTA

1. Formation of the decidua during implantation. The endometrium directly

subjacent to the implanting embryo is termed the decidua basalis, while that
which envelops the invading blastocyst is the decidua capsularis. Uterine wall
distant from the implantation site is the decidua parietalis.

2. Development of the chorionic villi. As soon as the extraembryonic

mesoderm forms (beginning of 3rd week), it pushes into the primary chorionic
villi. Blood vessels soon appear within the villi, which connect with the embryonic
circulation as soon as it begins (23-24 days). A villus that contains only
extraembryonic mesoderm is referred to as secondary; after embryonic
capillaries invade the mesoderm the villus is termed tertiary. Therefore, from
about 3-20 weeks of pregnancy four layers intervene between maternal and fetal
blood: synciotrophoblast, cytotrophoblast, mesodermal connective tissue, and
fetal capillary endothelium. This is the condition characteristic of the
epitheliochorial placenta of most mammals. At about 15 weeks, mesoderm and
cytotrophoblast begin to erode, leaving fetal blood vessels in direct contact with
syncytiotrophoblast. After 20 weeks this layer becomes very thin, forming the
placental membrane as the only barrier between maternal and fetal blood. Thus,
humans (as well as other primates, and rats) have what is called a hemochorial
placenta. Note that at no stage in any type of placenta does maternal and fetal
blood actually mix.
C. MECHANISMS OF TRANSFER OF SUBSTANCES ACROSS THE
PLACENTA

1. Simple diffusion: always down a concentration gradient; requires no

metabolic energy, limited to ions and small molecules such as H2O and CO2.

2. Facilitated diffusion: transport at a faster rate than simple diffusion,

generally down a concentration gradient but aided by lipid solubility or a carrier in
the membrane; sugars, some amino acids and some salts cross the placenta by
facilitated diffusion.

3. Active transport: may occur up a concentration gradient; requires

metabolic energy and a specific molecular transport mechanism; some amino
acids and divalent cations are actively transported.

4. Pinocytosis: trophoblastic cells can form intracellular vacuoles by

engulfing small quantities of maternal plasma with whatever particulates and
solutes it contains. Such vacuoles can traverse the cell and eject their contents
into fetal circulation. It is presumably via this means that some polypeptide and
protein hormones, antigens and antibodies, and some infectious agents cross the
placenta.

D. PLACENTAL ENDOCRINE SECRETIONS

1. The alterations in hormone production that accompany pregnancy are

among the most remarkable recorded in human physiology. A pregnant woman,
at or near term, produces 15-20 mg estradiol-17∃, 50-100 mg estriol, 250-600
mg progesterone, 1-2 mg aldosterone, and 3-8 mg deoxycorticosterone (DOC)
per day. Furthermore, she has increased levels of plasma renin,
angiotensinogen, angiotensin II, human placental lactogen (hPL) and she
synthesizes massive amounts of human chorionic gonadotrophin (hCG). All of
these hormones are produced in large part by the placenta.

2. The placenta produces two principal steroid hormones: progesterone and

estrogen. The blastocyst can synthesize small amounts of these hormones. But
the placenta becomes the dominant source of steroid hormones at the 8th week
of pregnancy. During the first 4 weeks, the level of progesterone in the maternal
serum rises as a result of secretion by the corpus luteum. By the 5th week, 17-
OH-progesterone (which is not secreted by the placenta) decreases, whereas
after this time the levels of hCG increase dramatically to the 10th week of
pregnancy. After the first 3-4 weeks, large quantities of estrogen are produced,
nearly all by the trophoblast. The placenta is rich in cytochrome P-450; this
oxygen acceptor is involved in the synthetic reaction sequences of both
progesterone and estrogen.
 3. Among the protein hormones produced by the placenta are hCG, hPL,
ACTH, TRH and LHRH. The glycoprotein hormone hCG is secreted by the
syncytiotrophoblast, and its secretion is probably stimulated by a placenta-
specific hormone that looks something like both LARHS and GnRH and is
synthesized in the cytotrophoblast. Synthesis of hPL, a single-chain polypeptide
hormone (191 amino acids) can be detected by the 14th day of pregnancy, i.e.,
5-10 days after implantation. As pregnancy advances, its rate of secretion (1
g/day) is greater than that of any other protein hormone, accounting for 10% of
all placental protein synthesis at term.

E. LECTURE OBJECTIVES

1. Be able to cite from memory the major functions of the trophoblast-derived

extra-embryonic tissues.

2. Be prepared to describe the timing of the major events in the formation of

the chorionic villi and the placenta.

3. Be able to define or describe in a few sentences each of the following terms:

decidua basalis, decidua capsularis, decidua parietalis, primary villus, secondary
villus, tertiary villus, chorion laeve, chorion frondosum, placental membrane,
placental septum, intervillous space, spiral endometrial artery.

4. Be able to cite four mechanisms of transfer of substances across the

placental barrier.