Natural Killer Cell Reduction and Uteroplacental Vasculopathy.

Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum.

The role of invasive trophoblast in implantation and placentation of primates.

We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast.

Risk of obstetrical complications in organ transplant recipient pregnancies.

Pregnancy after kidney and liver transplantation is becoming relatively common, although, in both groups, maternal complications are higher than in the general population. Both mean gestational age and mean birthweight seems significantly greater for liver transplant versus kidney transplant recipients and the risk of hypertension during pregnancy seems also lower for liver transplant than kidney transplant recipients. Thus, sequelae of chronic kidney diseases have stronger adverse effects on pregnancy, leading to a higher occurrence of adverse neonatal complications.

Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats.

Pregnant women who subsequently develop preeclampsia are highly sensitive to infused angiotensin (Ang) II; the sensitivity persists postpartum. Activating autoantibodies against the Ang II type 1 (AT(1)) receptor are present in preeclampsia. In vitro and in vivo data suggest that they could be involved in the disease process.

Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3beta.

Functional diversity of protein phosphatase 2A (PP2A) enzymes mainly results from their association with distinct regulatory subunits. To analyze the functions of one such holoenzyme in vivo, we generated mice lacking PR61/B'δ (B56δ), a subunit highly expressed in neural tissues. In PR61/B'δ-null mice the microtubule-associated protein tau becomes progressively phosphorylated at pathological epitopes in restricted brain areas, with marked immunoreactivity for the misfolded MC1-conformation but without neurofibrillary tangle formation.

Endovascular trophoblast and preeclampsia: A reassessment.

Since the earliest report on impaired spiral artery remodelling in preeclamptic human pregnancies, numerous studies have been devoted to possible mechanisms of impaired trophoblast invasion. A better knowledge of early uteroplacental blood flow has provided a physiological context for the processes of spiral artery invasion and associated remodelling, revealing a closely timed relationship between increasing flow and early steps in vascular remodelling. Concerning the impaired trophoblast invasion in preeclampsia, it has also to be considered that impaired invasion not only concerns invasion depth per se, but also the extension of this deep invasion from the central towards the more lateral spiral arteries of the placental bed.

The "Great Obstetrical Syndromes" are associated with disorders of deep placentation.

Defective deep placentation has been associated with a spectrum of complications of pregnancy including preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. The disease of the placental vascular bed that underpins these complications is commonly investigated with targeted biopsies. In this review, we critically evaluate the biopsy technique to summarize the salient types of defective deep placentation, and propose criteria for the classification of defective deep placentation into 3 types based on the degree of restriction of remodeling and the presence of obstructive lesions in the myometrial segment of the spiral arteries.

Evolution of invasive placentation with special reference to non-human primates.

It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae and even tarsiers and New World monkeys show restricted trophoblast invasion.

Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia-novel aspects for atherosclerosis and future cardiovascular health.

Preeclampsia is a common and potentially lethal pregnancy complication for women and offspring. Women who develop preeclampsia also run a long-term augmented risk of cardiovascular disease and premature death, and two theories are discussed. Women developing preeclampsia and persons developing cardiovascular disease may have common risk factors, which are unmasked by the "stress" of pregnancy.

Inhibition of trophoblast-induced spiral artery remodeling reduces placental perfusion in rat pregnancy.

Rats harboring the human angiotensinogen and human renin genes develop preeclamptic features in pregnancy. The preeclamptic rats exhibit a deeper trophoblast invasion associated with a reduced resistance index by uterine Doppler. Doxycycline inhibits matrix metalloproteinase activity.

Pre-eclampsia.

Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. It is a pregnancy-specific disease characterised by de-novo development of concurrent hypertension and proteinuria, sometimes progressing into a multiorgan cluster of varying clinical features. Poor early placentation is especially associated with early onset disease.

Effects of circulating and local uteroplacental angiotensin II in rat pregnancy.

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not.

The enigmatic uterine junctional zone: the missing link between reproductive disorders and major obstetrical disorders?

While there is a growing realization that the origins of major obstetrical complications associated with defective deep placentation, such as pre-term labour, fetal growth restriction and pre-eclampsia, may lie in the very early pregnancy events, the underlying mechanisms are not understood. Impaired deep placentation is foremost a vascular pathology, characterized by a lack of endovascular trophoblast invasion and remodelling of a segment of the spiral arteries embedded within the inner myometrium of the uterus. Outside pregnancy, the inner myometrium represents a highly specialized, hormone-dependent structure, termed the junctional zone (JZ), which plays an integral part in the implantation process.

A role for menstruation in preconditioning the uterus for successful pregnancy.

Menstruation is widely viewed as serving no purpose other than to reinitiate the endometrial cycle in the absence of pregnancy. Yet, it is striking that cyclic endometrial decidualization followed by menstrual shedding is confined to the few species, including human beings, where placenta formation entails deep trophoblast invasion of maternal tissues and its vasculature. Both menstruation and pregnancy are inflammatory conditions that cause a degree of physiological ischemia-reperfusion tissue injury, albeit much more so in pregnancy.

Fetal-maternal conflict, trophoblast invasion, preeclampsia, and the red queen.

The much publicized conflict hypothesis for understanding fetal-maternal interaction during pregnancy often invokes a 'battle' metaphor, rather than a well orchestrated interplay occurring as a series of well controlled moves and counter-moves as happens in a game of chess. Such stepwise interaction is particularly obvious in the spiral artery remodelling process, and it would be interesting to trace the history of the successive steps in histological adaptation throughout primate phylogeny. The restricted invasion observed in a few species on a 'lower' evolutionary scale suggests a tendency of progressive deeper invasion during primate evolution.

Trophoblasts reduce the vascular smooth muscle cell proatherogenic response.

Maternal spiral artery remodeling is the consequence of controlled trophoblast invasive interaction with the maternal cellular environment and is fundamentally important for successful placentation. In preeclampsia, trophoblast invasion is shallow, remodeling is incomplete, and vessels develop an inflammatory appearance, termed "acute atherosis." We noted that, in our preeclampsia, human renin-human angiotensinogen transgenic rat model, complement component 3 (C3), and tumor necrosis factor-alpha were upregulated and heavily expressed in atherotic uteroplacental vessels.

Uterine vascular function in a transgenic preeclampsia rat model.

We investigated intrauterine growth restriction, endothelial function, and uterine artery blood flow characteristics in a transgenic preeclampsia rat model with an activated renin-angiotensin system. We compared preeclamptic Sprague-Dawley (SD-PE) rats with normal pregnant Sprague-Dawley and nonpregnant Sprague-Dawley rats. We used transabdominal ultrasound and found that SD-PE rat embryos developed intrauterine growth restriction.

In vivo analysis of trophoblast cell invasion in the human.

In vivo analysis of trophoblast cell invasion is highly dependent on histological techniques, which are amply described in standard textbooks. The emphasis of this chapter therefore lies on material collection and interpretation of tissue sections, rather than on histological techniques per se. Proper identification of vascular structures on placental bed histological sections is important, the more because invading trophoblastic cells induce significant structural changes in uterine blood vessels, which may be disturbed in complicated pregnancies.

Morphometry of the basal plate superficial uteroplacental vasculature in normal midtrimester and at term.

Uteroplacental (UP) vascular arterial pathology has been associated with pregnancy complications. UP arterial structure has been characterized in placental bed biopsies, at the decidual-myometrial junction. Basal plate UP arteries, which are delivered with the placenta and thus routinely available, are not well characterized.

Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia.

We used rats transgenic for the human angiotensinogen (hAogen) gene and the human renin (hRen) gene and crossed the strains to produce a model of preeclampsia in the dams. The female (n=9) hAogen x male hRen cross had severe (telemetry-measured) hypertension and albuminuria, which developed during the last trimester of pregnancy and subsided after delivery. The converse cross (n=9) and control (n=9) SD rats did not.

Quantitative analysis of trophoblast invasion in preeclampsia.

Background: The process of physiological conversion of spiral arteries is dependent on the invasion of the interstitium and spiral arteries of the uterine wall by invasive extravillous trophoblast thereby creating a high flow-low resistance vessel. Quantitative data on restriction of trophoblast invasion and failure of spiral artery transformation are limited in preeclampsia.

Aim: This study morphometrically analyzes interstitial trophoblast cells and trophoblast cells embedded in the wall of the converted spiral arteries within the decidua and myometrium of normotensive and preeclamptic Black African pregnant women.