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 abruption 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 remodelling and the presence of obstructive lesions in the myometrial segment of the spiral arteries.

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Objective— The investigation of the histology of the placental bed spiral arteries in normal pregnancy and in pregnancies complicated by hypertension, with or without proteinura. Design— An observational study, based on women having caesarean sections for clinical reasons. Subjects— 17 normal pregnant women, 43 with gestational hypertension, of whom 39 had proteinuria, 17 with chronic hypertension, of whom 6 had proteinuria, and 5 with unclassified hypertension. Interventions— Placental bed biopsies obtained during caesarean section. Main outcome measures— Histological appearance of sections stained with haematoxylin and eosin PAS and Lendrum's MSB. Results— Biopsies containing spiral arteries were obtained from 6 normotensive and 44 hypertensive women. Trophoblastic invasion was present in 5 of the 6 normotensive biopsies but absent in the majority of those with hypertension. Subintimal proliferation was seen in all the normotensive biopsies but in only 8 of 28 from those with gestational hypertension and proteinuria. Other features seen predominantly or only in the hypertensive biopsies, in order of frequency, were medial hyperplasia, fibrin deposits, acute atherosis, endothelial vacuolation and thrombosis. Conclusion— Absence of physiological changes may not be peculiar to preeclampsia but may be associated or even a result of various forms of hypertension in pregnancy. Spiral arteries show a spectrum of changes in hypertensive pregnancies that do not appear to bear a clear‐cut relation to the clinical signs.

Abstract-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 (nϭ9) hAogen ϫ 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 (nϭ9) and control (nϭ9) SD rats did not. We demonstrated that the female hAogen ϫ male hRen cross had agonistic antibodies capable of activating the angiotensin (Ang) II AT1 receptor (AT1R-AA) and defined the epitope on the receptor's second extracellular loop. The phenomenon also occurs in humans with preeclampsia. The rats displayed renal histology reminiscent of preeclampsia, including fibrin deposition confined to the glomeruli. The complement system was activated in glomeruli and IgG deposits were present that may represent AT1R-AA. Finally, we observed an atherosis-like lesion in the spiral arteries of the placental bed, which we called placental-bed arteriolosclerosis. Our model may be relevant to preeclampsia in humans. Key Words: preeclampsia Ⅲ rats, transgenic Ⅲ antibodies Ⅲ immune systems Ⅲ renin-angiotensin system P reeclampsia, proteinuria, and severe hypertension in the latter part of pregnancy affects Ϸ3% of women in industrialized nations and a much higher percentage of women in underdeveloped countries. 1 In all countries, preeclampsia represents the major cause of maternal and fetal morbidity and mortality. Constructing a suitable animal model has been difficult. Takimoto et al described hypertension induced in pregnant mice by placental renin and maternal angiotensinogen. 2 Mice were generated transgenic for the human renin (hRen) and human angiotensinogen (hAogen) genes. The rodent and human renin-angiotensinogen systems do not interact and single transgenic animals are normotensive. Severe hypertension develops in double-transgenic offspring. The investigators observed that hypertension developed in the latter third of pregnancy in hAogen dams mated with hRen males. They showed that secreted active hRen of placental origin was capable of reacting with hAogen in the dams to produce angiotensin (Ang) II. Takimoto et al suggested that the transgenic mice might offer a unique model of "genetically induced" preeclampsia. 2 We showed that the same phenomenon exists in a rat transgenic model. 3 We used telemetric blood pressure measurements in that study to document the precise timing of the model; however, we presented no functional or histological data. 3 We have also studied preeclamptic women and found that they produce an agonistic antibody to the Ang II receptor (AT1R). 4,5 These autoantibodies (AT1-AA) activate the receptor. The activation sets into motion a chain of signaling events that could be responsible for the clinical disease. 6 We have now restudied our transgenic animal model and have observed that the rats also have these novel autoantibodies. MethodsSprague-Dawley (SD) rats harboring the human Aogen...

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Deep placentation in human pregnancy is realised by deep invasion of the placental bed by the extravillous trophoblast, involving the decidua and the inner (junctional zone) myometrium. Interstitial invasion of the stroma and endovascular trophoblast invasion of the spiral arteries both occur. Deep endovascular trophoblast invasion into the myometrial segments of spiral arteries is important for proper placental functioning. Before this extended vascular invasion begins, decidua-associated vascular remodelling, which includes swelling and disorganisation of the vascular smooth muscle, occurs during a period of rising placental oxygen. This early remodelling step may accommodate the progressively increasing maternal blood flow to the developing placenta. The subsequent trophoblast-associated remodelling step enhances and stabilises the widening of the vessels, whereas the vascular smooth muscle and elastic lamina are replaced by a fibrinoid matrix with embedded trophoblast. Defective deep remodelling contributes to placental malfunctioning in complications of pregnancy.

The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal-mild endometriosis with 95% sensitivity, 100% specificity and 97.5% accuracy. To confirm our findings, prospective studies are required.