A novel serine protease of the mammalian HtrA family is up-regulated in mouse uterus coinciding with placentation

This paper characterizes a novel gene, previously identified as uniquely regulated at implantation in mouse uterus. We cloned its full mRNA sequence encoding a serine protease possessing an IGF-binding domain and named it pregnancy-related serine protease (PRSP). PRSP is structurally similar to mammalian HtrA1 (56% amino acid similarity). Northern analysis revealed that the expression of PRSP mRNA was low before pregnancy, but it was increased at implantation and markedly up-regulated post-implantation. In-situ hybridization localized low levels of mRNA expression to the epithelium and stroma during very early pregnancy, but high expression to the decidual cells on day 8.5, primarily at the mesometrial pole where the placenta was forming. By day 10.5, PRSP mRNA was detected in the placenta. We also cloned an alternatively spliced PRSP mRNA that is expressed at a very low level. We located PRSP gene on chromosome 5 and established its intron/exon structure, which unambiguously explains how the two mRNA variants are produced through alternative splicing. Based on PRSP protein domain structure and its unique expression during pregnancy, we propose that PRSP plays an important role in the formation/function of the placenta.     

Effects of placentation on selected type A behaviors in adult males in the national heart,lung, and blood institute (NHLBI) twin study

A dermatoglyphic index derived from monozygotic (MZ) twins of known placental type was used to estimate placentation retrospectively in a sample of adult male MZ twins. Examination of behavioral test scores with respect to placentation showed that the within-pair difference of most measures of type A behavior was smaller in presumed monochorionic than presumed dichorionic pairs. Measures of cognitive function and hostility were not related to placental type. Intraclass correlations in the monochorionic subgroup of MZ twins were greater than the correlations reported for the full sample of MZ twins. The trends were strongest for the Adjective Check List scales taken at two different exams 5 years apart and, to a lesser extent, for the Framingham type A scale. Our results are most consistent with greater intrauterine environmental covariance in monochorionic MZ twins as an explanation for inflation of the MZ twin correlation relative to dizygotic (DZ) correlation reported for some type A measures.     

The use of cell salvage in women undergoing cesarean hysterectomy for abnormal placentation

BackgroundAlthough transfusion of autologous blood obtained from cell salvage has increased, its role in obstetric practice remains controversial. This case series reports the use of cell salvage in an attempt to avoid allogeneic transfusion in women undergoing cesarean hysterectomy for placenta accreta.MethodsThis prospective observational study, conducted in a large public maternity hospital, included 41 women with an antenatal diagnosis of placenta accreta, of whom 20 underwent cesarean hysterectomy and 15 received autologous blood after cell salvage. Intraoperative cell salvage was used for autologous blood transfusion, and salvaged blood was monitored for prewash and postfiltration squamous cells, fetal hemoglobin, and potassium concentration. Pre- and postoperative hemoglobin, platelet count and coagulation profile were compared.ResultsTwenty women underwent caesarean hysterectomy. Cell-salvaged blood was collected in 18 women and re infused in 15 women (83.3%). The mean volume of reinfused salvaged blood was 1476 ± 247 mL. Mean potassium concentrations (1.4 ± 1.2 versus 3.7 ± 0.42 mEq/L) and median squamous cell counts (0 [0–1] versus 8 [3–12]/high power field) were significantly lower postfiltration compared to prewash values. There were no instances of intraoperative or postoperative amniotic fluid embolism, hypotension, sepsis or coagulopathy. Of the 15 women who received autologous blood, 13 (86.7%) did not require allogeneic red blood cell transfusion.ConclusionsAutologous transfusion of salvaged blood can be used to minimize allogeneic transfusion in women undergoing cesarean hysterectomy for placenta accreta.     

Growth characteristics of diabetic rat ectoplacental cones in vivo and in vitro

Aims/hypothesis. To investigate the outgrowth of the ectoplacental cone in diabetic rats in vivo and in vitro.¶Methods. Female Wistar rats were injected intraperitoneally with streptozotocin (75 mg/kg body weight, n = 15), or with control buffer (n = 27) 3 days before mating. On day 9 (day 1 = copulation plug) decidual swellings were weighed and the volume and mitotic index of the embryo and ectoplacental cone were estimated. Also, ectoplacental cones were cultured either in the presence of decidual cells from pseudopregnant diabetic rats or in high glucose concentration media. Cultures were evaluated by the daily outgrowth and by the proportion of giant cells and proliferating cells on day 5.¶Results. In diabetic rats on day 9, the weight of the decidual swellings and the mitotic index in the ectoplacental cone were lower compared with controls (p < 0.0001 and p < 0.05, respectively). In vitro, control ectoplacental cones in the presence of decidual cells from diabetic rats showed a slight reduction in outgrowth on day 3 and 5 of culture. Outgrowth of diabetic ectoplacental cones in high glucose concentration medium was impaired on day 1 (p < 0.0005) compared with control ectoplacental cones in control medium, and on day 1 and 2 (both p < 0.005) compared with control ectoplacental cones in high glucose concentration medium. In control medium, the outgrowth of diabetic ectoplacental cones was impaired on day 1 (p < 0.05), compared with control ectoplacental cones. Proliferation was stimulated in diabetic ectoplacental cone cultures.¶Conclusion/interpretation. These data suggest that the outgrowth of diabetic ectoplacental cones is impaired by high glucose concentrations. [Diabetologia (2000) 43: 939–945]     

The role of alpha(5)beta(1)-integrin in the IGF-I-induced migration of extravillous trophoblast cells during the process of implantation

The role of integrins in the processes of adhesion and migration makes them attractive potential participants in the complex events of embryo implantation and placentation. Recently, the role of the alpha(v)beta(3)-integrin pathway was shown in the insulin-like growth factor-I (IGF-I)-stimulated migration of extravillous trophoblast (EVT) cells. This study was designed to investigate the role of alpha(5)beta(1)-integrin in this respect. Using cultured EVT cells, migration assays were carried out for IGF-I-treated or untreated cells in the presence or absence of the GRGDSP and GRGESP hexapeptides, alphaIR3, and a blocking antibody against alpha(5)beta(1)-integrin. Immuno-electron microscopy and immunofluorescent staining were performed to localize the distribution of alpha(5)beta(1)- and alpha(v)beta(3)-integrins, Rab5a, paxillin, phospho-FAK (pFAK), and vinculin. The results showed that IGF-I-induced migration of EVT cells was abolished following treatment with GRGDSP hexapeptide, alphaIR3, and a blocking antibody against alpha(5)beta(1)-integrin. Further, statistical analysis showed that the area-related numerical density of the alpha(5)beta(1)-integrin in the perinuclear regions was significantly higher than in the cell extensions. Immunocytochemical experiments demonstrated an up-regulation in internalization rate of alpha(5)beta(1)-integrin in IGF-I-stimulated EVT cells. Furthermore, alpha(5)beta(1)-integrin exhibited co-localization with Rab5a, but not with alpha(v)beta(3)-integrin, pFAK, paxillin, and vinculin at the focal adhesions of the EVT cells. Taken together, these findings suggest an essential role for alpha(5)beta(1)-integrin in IGF-I-promoted migration of EVT cells. It is possible therefore that IGF-I-induced internalization of alpha(5)beta(1)-integrin may be an important event during the migration of EVT cells in the complex processes of implantation and placentation.     

Decreased endovascular trophoblast invasion in first trimester pregnancies with high-resistance uterine artery Doppler indices

BACKGROUND: Defective trophoblastic invasion in early pregnancy is involved in the pathogenesis of pre- eclampsia. This study investigates the relationship between Doppler assessment of uterine artery resistance and endovascular trophoblastic invasion in the first trimester of pregnancy. METHODS: Patients undergoing termination of pregnancy for non-medical reasons were categorized as having a low- or high-resistance uterine artery blood flow pattern by transabdominal Doppler ultrasound. Products of conception were examined histologically with regard to the extent of decidual endovascular trophoblast invasion. RESULTS: There were 14 low-resistance and 17 high-resistance uterine artery blood flow pregnancies identified at 10-14 weeks of gestation. Normal intradecidual endovascular trophoblast invasion was identified with a similar frequency in both groups (P=0.79). However, the proportion of decidual vessels with endovascular trophoblast invasion was significantly higher in the low-resistance pregnancies (49%) compared with the high-resistance ones (34%, P=0.02). CONCLUSIONS: The findings of this study support the use of uterine artery Doppler investigation for the non-invasive assessment of trophoblast invasion in early pregnancy. Further studies are necessary to clarify the biological significance of these observations and their potential clinical applications.     

Placenta percreta in week 10 of pregnancy with consecutive hysterectomy: case report

Placenta percreta in early pregnancy is rare and has been documented in only a few cases. We report on a patient with abdominal pain in week 10 of pregnancy. Sonography revealed a defective embryonic development and the absence of a border line between trophoblast and myometrium, as well as invasive growth in the region of isthmocervical transition, so curettage was performed. Heavy bleeding at this stage made a hysterectomy necessary. Histological examination revealed a placenta percreta. Because of possible complications, the therapy of choice for a placenta percreta is a hysterectomy, as was performed in this case.     

A guide towards pre-pregnancy management of defective implantation and placentation

Pregnancy complications such as pre-eclampsia, placental abruption and growth restriction were once thought to represent end-of-pregnancy issues. Currently, the cause of such complications are being increasingly recognised as defective implantation and placentation. The molecular mechanisms responsible for normal and abnormal implantation are an area of active investigation. Screening tests, such as Doppler ultrasound of the maternal uterine arteries and evaluation of markers in the maternal serum, are being assessed to determine if such tests might allow for better recognition and, perhaps, prevention of many pregnancy complications related to abnormal placentation. Many techniques during pregnancy have been used to prevent pregnancy complications such as pre-eclampsia. Most have been unsuccessful. Ultimately, the solution may reside in pre-pregnancy approaches to improve implantation and placentation. Such approaches are actively being investigated and have promise.     

REVIEW ARTICLE: Immunology of Pre‐Eclampsia

Citation Redman CWG, Sargent IL. Immunology of Pre‐eclampsia. Am J Reprod Immunol 2010 Pre‐eclampsia develops in stages, only the last being the clinical illness. This is generated by a non‐specific, systemic (vascular), inflammatory response, secondary to placental oxidative stress and not by reactivity to fetal alloantigens. However, maternal adaptation to fetal (paternal alloantigens) is crucial in the earlier stages. A pre‐conceptual phase involves maternal tolerization to paternal antigens by seminal plasma. After conception, regulatory T cells, interacting with indoleamine 2,3‐dioxygenase, together with decidual NK cell recognition of fetal HLA‐C on extravillous trophoblast may facilitate placental growth by immunoregulation. Complete failure of this mechanism would cause miscarriage, while partial failure would cause poor placentation and dysfunctional uteroplacental perfusion. The first pregnancy preponderance and partner specificity of pre‐eclampsia can be explained by this model. For the first time, the pathogenesis of pre‐eclampsia can be related to defined immune mechanisms that are appropriate to the fetomaternal frontier. Now, the challenge is to prove the detail.     

The renin–angiotensin system from conception to old age: the good,the bad and the ugly

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