Ultrastructural changes of the placenta in cases of preeclampsia

The placenta plays vital roles during fetal development and growth. The ultrastructure of the placenta together with remodeling of the uterine spiral arteries are very important to maintain the utero-placental blood flow. Preeclampsia (PE) is a multifactorial disorder with abnormal placentation affecting the mother and fetus. The aim of this study was to study the ultrastructural abnormalities of the placenta in cases of PE. The placentas of 10 PE women and 10 controls were studied. Women of PE group were delivered by caesarian section while seven control women were delivered vaginally, and three by caesarian section. Placental samples were studied both morphologically and histologically by light and transmission electron microscopy. Light microscopic study of control placentas showed numerous microvilli, few syncytial knots, thin-walled blood vessels. PE placentas showed reduced number of microvilli with numerous syncytial knots, thick-walled vessels, edematous spaces, fibrotic areas and fibrinoid degeneration. Electron microscopic study of the control placentas showed a thick layer of syncytiotrophoblast (Sy), numerous microvilli and a thin layer of cytotrophoblast (Cy). PE placenta showed hypertrophy of Cy with atrophy of Sy and scarce microvilli. The trophoblast showed edematous vacuoles and glycogen storage areas. The villous core had congested capillaries, edematous spaces, glycogen storage areas and widespread areas of fibrosis. All the changes in PE placentas were attributed to hypoxia and oxidative stress and reduced utero-placental flow due to abnormal remodeling of the uterine spiral arteries that was aggravated by the thick placental barrier and the presence of edema, fibrosis and glycogen storage areas.

Comparison of prenatal functional markers of retardation of fetal growth and delayed fetal development with expression of vascular growth factors in the placenta

AIM: The study aimed to investigate and compare Doppler metric indicators in the main arteries of the functional system of the mother, placenta, and fetus as well as the parameters of the activityrest cycle in fetuses with vascular endothelial growth factor (VEGF) expression and placenta growth factor (PlGF) in the presence of physiological pregnancy and placental insufficiency to analyze morphofunctional parallels between these indicators in the third trimester of pregnancy. MATERIALS AND METHODS: Twenty-nine women on the 3435 weeks of pregnancy (period of physiological maturity of the activityrest cycle in the fetus) were screened. The main group consisted of 19 patients. The inclusion criteria were as follows: single-fetal pregnancy, fetometric indicators below the 10th percentile, and presence of blood flow disorders in the main vessels of the motherplacentafetus functional system. The comparison group included 10 relatively healthy women. The criteria for inclusion in the comparison group were as follows: single-fetal physiological pregnancy, fetometric indicators above the 10th percentile, and absence of Doppler disorders of placental blood flow. Fetometry and Doppler studies of the placental blood flow in the main arteries of the functional system of the mother, placenta, fetus were performed using the Voluson 730 Expert ultrasound device (GE, USA). The activityrest cycle in the fetus was evaluated using Sonicaid Team Care fetal monitor (Oxford, UK). Placental tissue was taken from the central placental area for immunohistochemical analysis of VEGF and PlGF expression with primary monoclonal antibodies of the main women group and comparison group after childbirth (1:100, Abcam, UK). RESULTS: A direct correlation between the expression of VEGF in the central zone of the placenta and index resistance (IR), ripple index (RI) in the uterine arteries, as well as the cerebroplacental relationship CPR (r1=0.487; p1=0.035; r2=0.487; p2=0.035; r3=0.578; p3=0.030, respectively) in women of the main group was found. A direct correlation was established between the expression of VEGF in the central zone of the placenta and IR in the umbilical artery (r=0.49; p=0.033) in patients of the main group. The analysis of the restactivity cycle in fetuses of women of the main group showed that at 3435 weeks 73% of them do not form it: the behavior of fetuses is represented only by the activated state. An inverse relationship was found between VEGF expression and the motor-cardiac reflex amplitude (r=0.866; p=0.05) as well as the heart rate oscillation amplitude (r=0.866; p=0.05) in fetuses of women of the main group. CONCLUSIONS: The identified morphofunctional parallels will allow to develop non-invasive pathogenetic prognostic models for prenatal diagnosis of fetal development delay with different degrees of growth restriction.

Human placental perfusion measured using dynamic contrast enhancement MRI

Objectives To evaluate the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) and measure values of in vivo placental perfusion in women. Methods This study was part of the Placentimage trial (NCT01092949). Gadolinium-chelate (Gd) enhanced dynamic MRI was performed two days before termination of pregnancies at 16 to 34 weeks gestational age (GA). Quantitative analysis was performed using one-compartment intravascular modeling. DCE perfusion parameters were analyzed across GA and were compared in IUGR and AGA fetuses. Results 134 patients were enrolled. After quality control check, 62 DCE MRI were analyzed including 48 and 14 pregnancies with normal and abnormal karyotypes, respectively. Mean placental blood flow was 129±61 mL/min/100ml in cases with normal karyotypes. Fetuses affected by IUGR (n = 13) showed significantly lower total placental blood flow values than AGA fetuses (n = 35) (F total = 122±88 mL/min versus 259±34 mL/min, p = 0.002). DCE perfusion parameters showed a linear correlation with GA. Conclusions Measuring placental perfusion in vivo is possible using DCE MRI. Although this study has many limitations it gives us the first DCE MRI values that provide a potential standard for future research into placental perfusion methods and suggests that placental functional parameters are altered in IUGR pregnancies.

Effects of Mid-gestational L-Citrulline Supplementation to Twin-bearing Ewes on Umbilical Blood Flow, Placental Development, and Lamb Production Traits

The objective of the study was to examine how L-citrulline supplementation to ewes during mid-gestation influences placental activity, placental blood flow, lamb body weight and carcass characteristics. Two studies were completed. A pharmacokinetic study to compare circulating plasma amino acid concentrations after a single intravenous injection of 155 µmol/kg BW L-citrulline or after an isonitrogenous amount of L-alanine (control; 465 µmol/Kg BW). Increases (P < 0.05) in circulating citrulline concentrations were detected for 8 h after L-citrulline injection versus the control. Similarly, increases (P < 0.05) in circulating arginine concentrations were detected for 24 h after L-citrulline treatment. The second study used 12 ewes with twin pregnancies. Daily intravenous injections of either L-citrulline or L-alanine were administered for 39 d from d 42-45 to 81-84 of gestation. Ewes were limit-fed at 85 % daily energy requirements during the injection period. A decrease (P < 0.0001) in body weight was observed in both treatment groups during this period. No treatment differences were observed in circulating pregnancy-specific protein B concentrations or placental blood flow during the treatment and post-treatment gestational period. No treatment differences were observed in lamb survival nor in lamb birth, weaning and slaughter weights. Treatment did not influence lamb carcass composition or organ weights. However, there was a tendency (P = 0.10) for an increase in antral follicle numbers in ovaries from ewe lambs derived from ewes treated with L-citrulline. In summary, a daily L-citrulline injection increased both circulating citrulline and arginine concentrations in ewes, but daily L-citrulline injections during mid-gestation did not produce any detectable changes in placental activity and blood flow, neonatal and postnatal lamb development, and lamb carcass composition at slaughter. In conclusion, no benefits in placental function and lamb development were observed after providing L-citrulline during mid-gestation in ewes exposed to a mild energy restriction, but there was an indication that follicle numbers in ewe lambs were positively influenced by L-citrulline treatment during fetal development.

Changes in Umbilico–Placental Circulation during Prolonged Intact Cord Resuscitation in a Lamb Model

Some previous studies reported a benefit to cardiopulmonary transition at birth when starting resuscitation maneuvers while the cord was still intact for a short period of time. However, the best timing for umbilical cord clamping in this condition is unknown. The aim of this study was to explore the duration of effective umbilico–placental circulation able to promote cardiorespiratory adaptation at birth during intact cord resuscitation. Umbilico–placental blood flow and vascular resistances were measured in an experimental neonatal lamb model. After a C-section delivery, the lambs were resuscitated ventilated for 1 h while the cord was intact. The maximum and mean umbilico–placental blood flow were respectively 230 ± 75 and 160 ± 12 mL·min−1 during the 1 h course of the experiment. However, umbilico–placental blood flow decreased and vascular resistance increased significantly 40 min after birth (p < 0.05). These results suggest that significant cardiorespiratory support can be provided by sustained placental circulation for at least 1 h during intact cord resuscitation.

Resistance Training Does Not Decrease Placental Blood Flow During Valsalva Maneuver: A Novel Use of 3D Doppler Power Flow Ultrasonography

Background: The Valsalva maneuver may increase maternal blood pressure and intra-abdominal pressure, resulting in decreased blood flow to the fetus during resistance training. Hypothesis: There is no significant reduction in placental blood flow in pregnancy during resistance training in recreational athletes, as documented by a 3-dimensional power flow Doppler ultrasonography. Study Design: Cohort. Level of Evidence: Level 3. Methods: A cohort of healthy women who participated in recreational athletics was enrolled in a prospective study to assess placental blood flow during a resistance exercise. A 1 repetition maximum (1RM, up to 50 lb) was determined through a modified chest press as a marker of heavy resistance training. Three-dimensional volume measurements and power Doppler flow were determined at the rest phase and during the 1RM lift phase. The vascular flow index (VFI) was calculated to determine placental perfusion during each phase. Results: A total of 22 women participated. The mean age of participants was 31 years. Gestational age ranged from 13 to 28 weeks. Average 1RM weight lifted was 30 lb. Four women (18%) were able to lift 50 lb, the maximum weight that the study allowed. The remaining 18 women (82%) lifted their true 1RM. Mean VFI during lift phase was 2.185 compared with 2.071 at rest ( P = 0.03). There was a slight mean increase in VFI during lift phase, 0.114 (95% CI 0.009-0.182) from 2.071 to 2.185 with lifting ( P = 0.03). The 15 women who participated in structured exercise had a mean VFI at rest and during the lift phase of 2.031 and 2.203, respectively ( P = 0.01). Conclusion: Three-dimensional power flow Doppler imaging can guide resistance training during pregnancy to prevent fetal injury due to hypoperfusion. Resistance training up to an RM1 of 50 lb did not result in a significant reduction of placental blood flow from resting state in the study population. Clinical Relevance: This technique may be used to guide training parameters among pregnant athletes.