(03-01) Implantation

Question 1

(Nutritional Support of the pre-implantation embyro)

1. Prior to formation of the placenta the early embryo is supported by secretions of what?

Not only does this provide nutrition but it also directs what?

2. In species with superficial placental attachment (the epitheliochorial and synepitheliochorial placentas of pigs, horses and ruminants) histotroph remains an important source of nutrition for the embryo and fetus throughout what?
3. in primates, with their aggressively invasive placenta, it is still considered to provide significant nourishment for how long?
4. Production of histotroph appears to be under stimulatory control of both maternal progesterone and prolactin but also what?

Answer 1

1. the uterine glands

(the “uterine milk” or “histotroph” This is a mixture of amino acids, proteins, glucose, ions, growth factors and hormones.)

trophoblast growth and differentiation

2. gestation
3. first 1/3 of pregnancy
4. trophoblast derived interferons ( i.e the embryo directs the uterus to support its nutritional and developmental needs)

Question 2

(“Implantation”)

1. Implantation refers to the formation of what?
2. In most of our farmed domestic species it probably isn’t a good term because most of them don’t aggressively invade the uterine tissues (implant) as occurs in the rodents and primates, but instead remain fairly superficially attached

how about dogs?

Answer 2

1. he placenta that will support the embryo and fetus throughout pregnancy

intermediate between these two

Question 3

(“Implantation”)

1. what are the three (soetimes four) stages of implantation?
2. Is the uterine epithelium (endometrium) constantly receptive to the implanting embryo?

Answer 3

1. apposition

adhesion

attachement

invasion (in some)

2. no - There is an “implantation window” where the uterus is receptive, but before (pre-receptive) and after (post-receptive) this interval it is not. (You could replace “implantation window” with “attachment window” in farm species).

Question 4

(“Implantation” Cont)

1. Unlike rodents and primates, the embryos of domestic species do not attach to the uterus immediately (or almost so) on entry from the oviduct. As we saw earlier, they first grow and become spaced through the uterus.

During this stage, can the embryo adhere to the uterus?

what prevents adhesion?

expression of MUC-1 increased by what?

These glycoproteins form a barrier to adhesion by doing what?

What is the first thing that has to happen to allow apposition of the trophoblast and uterine cells?

Answer 4

1. no - he uterus is in its “pre-receptive” stage

mucin and other adhesion-inhibitng glycoproteins (MUC-1)

progesterone

preventing access to the cell adhesion molecules on the uterine epithelial cell surface

down-regulation or removal of these molecules

Question 5

(Implantation Cont)

1. The first thing that has to happen is down-regulation or removal of these molecules to allow apposition of the trophoblast and uterine cells.
2. The Signal that causes this varies by species

in rodents?

in farm animals?

Answer 5

2. increased estrogen

maintainted elevated levels of progesterone

(down regulates is own receptor –> results in down regulation of MUC-1 expression)

Question 6

(Implantation Cont)

1. Coincident with the down-regulation of MUC-1 there are changes in epithelial cell morphology.
2. These include the loss of what?

which result in what?

3. the uterus is now what?

these changes are also driven by what?

4. In the ruminants this is another function of interferon-τ

how about in other species?

Answer 6

2. microvilli

urther exposure of cell-surface adhesion molecules and production by both uterine epithelial cells and embryonic trophoblast of bridging ligands ((molecules that will bind the adhesion molecules))

3. receptive

he down-regulation of progesterone receptors and by trophoblast interferons

4. In other species the trophoblast produces different interferons, and while these don’t have a role in maternal recognition they are important in establishing the receptive status of the endometrium.

Question 7

(Implantation - cont)

1. Weak interactions between these modified uterine epithelial cells and the embryo now trigger an adhesion cascade, initially using what?
2. The cascade then activates or exposes what?
3. These adhesion molecules on the trophoblast and epithelial cells each bind to what?
4. Since you have the integrins of the embryo attached to one end of these ligands, and those of the uterine epithelium bound to the other end, the 2 epithelial structures, embryonic and uterine, are bound together. The adhesion is now stable and the embryo attached to the uterus.

Answer 7

1. weak interactions between surface carbohydrate molecules (selectins).
2. stronger adhesion molecules on the apical surface of the uterine epithelial cells, best described are the integrins, (which are also present on the trophoblast cells of the embryo.)
3. bridging ligands (such as fibronectin, vitronectin and osteopontin)

Question 8

1. In what species does the trophoblast does not do much in the way of invasion into the deeper layers of the uterus?
2. However, if you put these embryos outside the uterus (e.g. kidney) they do what?

They do this by producing what?

Answer 8

1. farm species

(The trophoblast of the pig and horse embryo shows no invasiveness and stays bound to the surface of the uterine epithelium)

2. are aggressively invasive

proteolytic enzymes (The uterus secretes protease inhibitors that limit this invasiveness)

Question 9

1. The uterine epithelium of ruminants consists of discrete areas (oval shaped) that are devoid of what?

these are termed what?

Between these the (non-caruncular) epithelium is what?

2. The embryonic trophoblast cells overlying the caruncular epithelium become what?

and then fuse with what to form what?

3. This only occurs over the caruncles, the embryonic side of this is termed a what?

caruncle + cotyledon = ?

Answer 9

1. uterine glands

caruncles

richly glandular

2. binucleate [by nuclear division without cytoplasmic division (cytokinesis)]

with epithelial cells to form multinucleated syncitial plaques

3. cotyledon

placentome

Question 10

1. In what - the blastocyst does gradually invade the uterine stroma to a greater or lesser degree.?
2. Once the embryo is attached the underlying uterine luminal epithelial cells undergo what?
3. In the carnivores this involves the cells of the trophoblast doing what?

Answer 10

1. carnivores, rodents, and primates
2. apoptosis
3. migrating between the uterine epithelial cells

(These uterine epithelial cells are subsequently phagocytosed resulting in the endotheliochorial placenta.)

Question 11

1. Penetration of the lumenal epithelium by invading trophoblast cells triggers responses in the underlying uterine stromal cells termed what?
2. he stromal cells hypertrophy and divide, transforming from small spindle shaped cells to what?
3. These cells have many functions and secrete numerous substances including what?

which act on what?

Answer 11

1. “decidualization”
2. arge polygonal cells with extensive contacts between them.
3. prolactin and IGHBP (IGF binding proteins)

gene networks that limit/control trophoblast invasion.

(There is evidence that control of cell fusion and invasiveness is due to expression of endogenous retroviral sequences present in the mammalian genome, and that accumulation of these may have had a role in the evolution of placentation.)

Question 12

(Placentation)

(Placental Functions)

1. Placenta carries out functions of what for the fetus?
2. does so by doing what?

Answer 12

1. lungs, gastrointestinal tract, kidneys, liver and some endocrine glands for the fetus
2. stealing what it needs from the mother’s circulation and then returning most waste products to her for disposal.

this pic is small type…

Question 13

(Placental Function)

(cont)

The barriers for this exchange are the tissue layers between the maternal and fetal blood.

1-3. On the maternal side these are…

4-6. On the fetal side they are…

Answer 13

1. The endothelium lining the capillary
2. Connective tissue
3. The uterine epithelium (endometrium)

(None or all of these may be present depending on species (degree of embryo invasiveness).)

4. The chorionic epithelium (outermost layer of the fetal tissue)
5. Connective tissue
6. The endothelium lining the capillary

(All of the fetal layers are present in all cases.)

Question 14

When placentas are classified on the basis of the maternal-fetal barrier the outermost maternal layer is written 1st (this is variable depending on how many layers the fetal tissues invaded through), followed by the outermost fetal layer, which is always the chorion.

(For each animal give pattern of chorionic villi/maternal-fetal barrier/maternal tissue loss at birth

NOW LOOK AT PICS ON PAGE 219 AND READ THE TEXT WHICH I:M SURE IS EXTREMELY IMPORTANT

Answer 14