Elizabeth M. Ramsey

Interactions of the trophoblast and maternal tissues in three closely related primate species

The confluence of maternal and fetal tissues to form the placenta causes a wide variety of alterations in cells of both origins. Three closely related primate species were studied for similarities and differences in the interrelationships formed during various stages of placental development in the areas of implantation, decidualization, and trophoblastic involvement in the spiral arteries. Although certain similarities exist among the three species a surprising number of distinct differences were found to shed doubt on the common practice of assuming species-to-species similarity, particularly among primates.

VASCULAR ADAPTATIONS OF THE UTERUS TO PREGNANCY

IL may be well, a t the outset, to dispel a misapprehension implied in the title of this discussion. Our orientation toward the cyclic changes in uterine vasculature i s quite false if we look upon pregnancy as an isolated event for which special and extraordinary preparations must be made. This attitude, which underlies more of our thinking than we are perhaps aware, stems from the preoccupation of both clinicians and investigators in the last few decades with the phenomena of the menstrual cycle. Analyses of “the cause of menstruation,” studies of “the mechanism of menstruation” have tended to set the menstrual cycle apart as a separate entity in the over-all reproductive pattern. By implication, pregnancy is also separate and different. That the two processes dovetail, that one is a “preparation” for the other, has not been doubted, but a sort of anatomical and physiological gear shifting has been assumed when pregnancy supervenes in the orderly succession of menstrual cycles. The accumulating data of recent investigations and their thoughtful interpretation in the framework of reproductive physiology as a whole indicate that no such dichotomy exists in fact or is justihed in concept, even as a matter of convenience in descript ion. The classic experimental studies of Daron,‘ 1 ’’ of Markee,3 and of Harlelmez,‘, 5 , made twenty years ago on the nonpregnant endometrium in the rhesus monkey and man, laid the foundations of our understanding of uterinc vascular physiology. Subsequent studies of placental vasculature at the laboratory of the Carnegie Institution of Washington and elsewhere, to be summarized in the present report, have approached the same basic problem from the other end. has interpreted the data obtained from these angles of approach and has Iirought clearly into focus 1 he fact that specific adaptations for pregnancy commence on day 1 of the menstrual cycle and form a smooth, uiihroken, purposeful sequence t hereafter. ‘I’he dual arlerial supply to the primate endometrium and the sensitivity 10 hormonal stimulation of the Type I (spiral or coiled) arteries that supply i t s superlicial one third are the pivotal factors in the cyclical behavior of the endometrium. This sensitivity is manifested during the fvllicular phase of the cycle by rhythmic dilatation and constriction of the superficial capillary bed supplied by the spiral arteries and in the progravid phase by rapid growth of these arteries when the blood level of corpus luteum hormone is high and b~7 vasoconstriction when the level is reduced. ’The rapid growth, outstripping that of the endometrial stroma, leads to increased coiling which, i n turn, retards circulation in the capillary bed with production of edema. The cmistric-tion of the arteries creates stasis and consequent ischemia and ex( r;ivxsat ion of blood. ‘These latter phenomena occur in d l cycles at ahout days 21 to 28, when the activity of the corpus luteuin i s commencing to wane. The cziusative vas:ocoiistric.tioii

INTERMITTENT FUNCTIONING OF THE UTEROPLACENTAL ARTERIES.

Abstract Repeated radioarteriographic placentograms carried out during uterine relaxation demonstrated alterations in the pattern of arterial entries visualized. Spurts appeared, or disappeared, independent of recorded myometrial activity or significant change in maternal blood pressure. The pattern of the variations was such that vasomotion of the arteries supplying the intervillous space seemed to be the most probable explanation for intermittent functional patency of the entries.

Venous drainage of the placenta in rhesus monkeys: Radiographic studies

Abstract 1. 1. Drainage from the intervillous space of the placenta has been studied in 41 rhesus monkeys by serial and cineradioangiography following introduction of contrast medium into the maternal arterial bloodstream and directly into the intervillous space. 2. 2. When dye is injected into the intervillous space during uterine relaxation, it drains promptly through venous orifices into the uterine mural veins and thence to the pelvic veins (primarily the ovarian veins). 3. 3. During uterine contraction, there is partial or complete disappearance of dye from drainage channels, but the size and configuration of the placental blood pool is maintained. 4. 4. Inflow through arterial channels is halted during contractions, and any dye spurts which may have begun to form are arrested until the contraction peak has passed. 5. 5. The study indicates the controlling role played by arterial inflow in the maintenance of placental circulation. Continuing inflow provides the impetus whereby blood is eventually pushed toward orifices of exit and drained into uterine and pelvic veins. When intrauterine pressure is raised by myometrial contractions, both inflow and outflow are reduced or even halted though the volume of blood in the intervillous space appears to be maintained, thus providing for continued (though reduced) maternal-fetal exchange.

Vascular patterns in the endometrium and the placenta.

At a conference dealing with research in small blood vessels a report of work upon the circulation of the placenta may seem to be insinuating itself under false pretenses, for the placenta can hardly be described as a &dquo;small&dquo; vascular channel, least of all the placenta of primates. However, if the physiology of the placenta is considered rather than its gross morphology, it is at once apparent that what the placenta does is identical with what microscopic blood vessels do, such as may be studied in the rat’s mesentery or the hamster’s cheek pouch or the wing membranes of the bat, for all are essentially terminal areas of metabolic exchange. To describe the vast intervillous

CINERADIOANGIOGRAPHIC VISUALIZATION OF THE VENOUS DRAINAGE OF THE PRIMATE PLACENTA IN VIVO.

Radiopaque dye injected directly into the intervillous space of the placenta of the rhesus monkey may be observed, by cineradiography, as it spreads throughout the space and drains into the veins of the uterine wall and eventually into the systemic circulation.

Placental Vasculature and Circulation in Primates

When the fertilized primate ovum, whether of human, monkey, baboon, or mangabey, comes to rest on the lining epithelium of the uterus, the trophoblast of its wall promptly begins to invade the endometrium over an ever widening base (Heuser and Streeter, 1941; Enders, 1976; Houston, 1969, 1975; Enders et al., 1983). This usually occurs in the immediate vicinity of a capillary (Figure 1). In the human the whole blastocyst sinks into the endometrial stroma while in nonhuman primates the implantation remains superficial (compare Figures 2 and 3). As the trophoblast encounters maternal capillaries in the course of its penetration of the endometrium it surrounds them, and they thus become one source of the lacunae which appear in the trophoblastic shell. The tissue spaces which develop between trophoblastic cells constitute the second source (Figures 3 and 4). These lacunae enlarge and intercommunicate. Further communication between them and the maternal vascular system is established as progressive trophoblastic invasion erodes maternal vessel walls. Maternal blood in the lacunae, propelled at first only by capillary pressure, moves sluggishly. With deeper penetration of the trophoblast endometrial spiral arteries are tapped. Blood from them enters the lacunae under higher pressure and thus the first stage of placental circulation is established.

The Effect of Anesthesia and Surgery in Pregnant Rhesus Monkeys

There is a growing need to define the physiologic ‘steady state’ in pregnant rhesus monkeys because of the increased demand for this experimental model in investigation of maternalfetal re