Placental Vascularization Research Articles

P14.09: Evaluation of placental vascularisation (by 3D power Doppler) at 11‐14 w, and their association with uterine arteries Doppler, PAPP‐A, BHCG and PlGF

<scp>P</scp>14.09: Evaluation of placental vascularisation (by <scp>3D</scp> power Doppler) at 11‐14 w, and their association with uterine arteries Doppler, <scp>PAPP</scp>‐A, <scp>BHCG</scp> and <scp>PlGF</scp>

New insights into the mechanism of PPARγ regulation of trophoblast invasion and placental vascularisation

New insights into the mechanism of PPARγ regulation of trophoblast invasion and placental vascularisation

Evidence of placental endoplasmic reticulum stress in the pathophysiology of gestational diabetes mellitus

Evidence of placental endoplasmic reticulum stress in the pathophysiology of gestational diabetes mellitus

Effects of a single course versus repeated courses of antenatal corticosteroids on fetal growth, placental morphometry and the differential regulation of vascular endothelial growth factor.

To investigate the impact of antenatal exposure to a single course or repeated courses of dexamethasone (DEX) on neonatal anthropometrics, placental morphometry and potential effect on maternal plasma levels and placental expression of vascular endothelial growth factor (VEGF). Pregnant women between 27 and 32 weeks of gestation who delivered between 28 and 40 weeks and received a single course (n = 38) or repeated courses (n = 33) of DEX were compared to gestational age-matched controls (n = 30). Maternal blood samples were obtained, and placental biopsy was taken. Area percent of VEGF immunostaining and villous capillarization index were evaluated using image analysis. Infants exposed to repeated courses of DEX were significantly associated with decreased birthweight, body length, head circumference and placental weight compared with controls (P = 0.011, P < 0.001, P = 0.004, P < 0.001, respectively) and with the group that received a single course of DEX (P = 0.021, P = 0.020, P = 0.049, P = 0.010, respectively). There was a significant decrease in maternal VEGF plasma levels and percentage of VEGF immunostained area after repeated courses of DEX compared with controls (P < 0.001 and P = 0.001, respectively) or a single course (P = 0.028 and P = 0.002, respectively). Notably, repeated courses of DEX impaired normal increase in villous capillarization index compared with controls or a single course (P = 0.001 and P = 0.041, respectively). Repeated antenatal courses of DEX compromised fetal and placental growth compared with a single course of DEX, and these effects were potentially mediated by altered maternal plasma levels and placental expression of VEGF with consequent decrease in placental vascularization. Because of continuing uncertainties, several key messages for clinicians are provided.

Ultrasound monitoring of fetal and placental growth and vascularisation in the rabbit

Several studies have assessed the quality of periodontal tissues adjacent to the second molar after extraction of third molars using clinical assessment and radiographs. In clinical practice, the space occupied by these molars is used to perform distalizing movements and tissue integrity is a condition to do it, so it is necessary to evaluate with suitable methods such as digital volume tomography alveolar bone quality, before and after the removal of third molars. The aim of the study was to evaluate through cone beam dimensions the distal alveolar bone of the second molar after third molar extractions in patients undergoing orthodontic treatment. A quasi-experimental study was implemented with a six months follow up in patients with orthodontic treatment that attended the post-graduate clinic of the University of Cartagena. The sample consisted of 128 molars of 32 individuals treated with fixed appliances. Bone dimensions behaved as follows: height was 3.44 mm T0, T1 of 3.96 mm and 3.44 mm in T2; the thickness was 2.90 mm T0, T1 was 2.79 mm and 3.37 mm T2; T0 width was 15.58 mm, 15.50 mm in T1 and T2 of 15.19 mm. The alveolar process can recover its dimensions after extraction thanks to dental movements generated by orthodontics thus maintaining a stability which results in periodontal health.Diversos estudios evalúan la calidad de los tejidos periodontales adyacentes al segundo molar después de la extracción de los terceros molares utilizando como método la valoración clínica y las radiografías. En la práctica clínica, el espacio ocupado por estos molares se usa para realizar movimientos de distalización y la integridad de los tejidos, es una condición para poder realizarlo, por lo que es necesario evaluar con métodos idóneos, como la tomografía volumétrica digital, la calidad del hueso alveolar, antes y después de la extracción de los terceros molares. El objetivo de la investigación fue evaluar a través de cone-beam las dimensiones de hueso alveolar distal del segundo molar después de la extracción de los terceros molares en sujetos sometidos a tratamiento de ortodoncia. Se implementó un estudio cuasiexperimental con seguimiento a seis meses, en pacientes con ortodoncia fija; que acuden a la Clínica de Postgrado de la Universidad de Cartagena. La muestra fue constituida por 128 molares de 32 individuos tratados con ortodoncia fija. Las dimensiones óseas se comportaron de la siguiente manera, la altura en T0 fue de 3.44 mm, en T1 de 3.96 mm y en T2 de 3.44 mm; el grosor en T0 fue de 2.90 mm, en T1 fue de 2.79 mm y en T2 de 3.37 mm; la anchura en T0 fue de 15.58 mm, en T1 de 15.50 mm y en T2 de 15.19 mm. El proceso alveolar puede recuperar sus dimensiones después de una extracción gracias a los movimientos dentales generados por ortodoncia, manteniendo una estabilidad que se traduce en salud periodontal.

Could 3D placental volume and perfusion indices measured at 11–14 weeks predict occurrence of preeclampsia in high-risk pregnant women?

Objective: Preeclampsia (PE) is a known cause of maternal, fetal and neonatal morbidity and mortality. Thus, evaluation of the predicting value of combining the 3D assessment of placental volume with the assessment of placental perfusion indices through 3D power Doppler (3DPD) at 11–14 weeks in pregnant women at high risk to develop PE could be a suitable screening method.Methods: 3D assessment of placental volume and 3DPD assessment of placental vascularization indices at 11–13 weeks and uterine artery Doppler scan (RI and PI) at 21–22 weeks were conducted in this prospective case–control study. Their predictive ability for PE was assessed.Results: One-hundred pregnant women divided into two groups were enrolled in our study. High-risk group (n = 50) and control group (n = 50). Thirty-eight (76%) patients in the high-risk group and 6.0 (12%) patients in the control group developed PE, respectively. The mean values of placental volume (<0.001), vascularization index (<0.001), vascularization flow index (<0.002) were significantly lower in the high-risk group. Meanwhile, uterine artery RI (0.011) and PI (<0.001) was significantly higher in the study group. Uterine artery PI is negatively correlated with placental volume and vascularization indices (−0.36).Conclusion: Our findings suggest that 3D placental volume measurement and 3DPD assessment of placental vascular indices in the first trimester has the potential to detect women at risk for subsequent development of PE.

Assessment of placental volume and vascularization at 11–14 weeks of gestation in a Taiwanese population using three-dimensional power Doppler ultrasound

BackgroundThe placental volume and vascular indices are crucial in helping doctors to evaluate early fetal growth and development. Inadequate placental volume or vascularity might indicate poor fetal growth or gestational complications. This study aimed to evaluate the placental volume and vascular indices during the period of 11–14 weeks of gestation in a Taiwanese population. MethodsFrom June 2006 to September 2009, three-dimensional power Doppler ultrasound was performed in 222 normal pregnancies from 11–14 weeks of gestation. Power Doppler ultrasound was applied to the placenta and the placental volume was obtained by a rotational technique (VOCAL). The three-dimensional power histogram was used to assess the placental vascular indices, including the mean gray value, the vascularization index, the flow index, and the vascularization flow index. The placental vascular indices were then plotted against gestational age (GA) and placental volume. ResultsOur results showed that the linear regression equation for placental volume using gestational week as the independent variable was placental volume = 18.852 × GA − 180.89 (r = 0.481, p < 0.05). All the placental vascular indices showed a constant distribution throughout the period 11–14 weeks of gestation. A tendency for a reduction in the placental mean gray value with gestational week was observed, but without statistical significance. ConclusionAll the placental vascular indices estimated by three-dimensional power Doppler ultrasonography showed a constant distribution throughout gestation.

PFM.15 Is there a role for Placental Volume, Vasculature and Calcification in monitoring Post-term Pregnancies?

ObjectivesThis study aims to assess if three dimensional power Doppler (3DPD) ultrasound of the placenta, evaluating placental volume, vascularisation, and blood flow in post-term pregnancies differs from normal. It also...

PFM.14 Placental Volume, Vasculature and Calcification in pregnancies complicated by pre-eclampsia and intra-uterine growth restriction

ObjectivesPre-eclampsia (PET) and intrauterine growth restriction (IUGR), often associated with impaired placental function, are among the most common conditions contributing to increased perinatal mortality and morbidity. This study investigates if...

Antihypertensive drugs methyldopa, labetalol, hydralazine, and clonidine improve trophoblast interaction with endothelial cellular networks in vitro

The interaction between trophoblasts and maternal endothelium is important for placental vascular modeling. Failure of uterine spiral artery transformation is linked to the etiopathology of preeclampsia. Antihypertensive medications used to control hypertension in early pregnancy can alter placental and circulating cytokines. This study investigated whether selected antihypertensive drugs can modulate the interaction between trophoblast and endothelial cells. Human uterine myometrial microvascular endothelial cells were preincubated with (or without) low-dose tumor necrosis factor-α (TNF-α; 0.5 ng/ml) or TNF-α and soluble fms-like tyrosine kinase 1 (sFlt-1; 100 ng/ml). Red fluorescent-labeled endothelial cells were then cultured on Matrigel. After appearance of endothelial cellular networks, green fluorescent-labeled HTR-8/SVneo trophoblast cells were cocultured in the presence of pharmacological doses of methyldopa, labetalol, hydralazine, and clonidine. Images were captured after 24 h and drug effects on HTR-8/SVneo cell integration were quantified by Image Analysis software. The conditioned medium was collected to measure sFlt-1, vascular endothelial growth factor (VEGF), placental growth factor, interleukin-10, and interleukin-6 by ELISA. Methyldopa, labetalol, hydralazine, and clonidine increased trophoblast integration into TNF-α-preincubated endothelial cellular networks. In conditioned medium, sFlt-1 was reduced by methyldopa, hydralazine, and clonidine alone. VEGF was increased by methyldopa. A decrease in placental growth factor was seen by methyldopa and also in nontreated endothelial cell coculture of the other three drugs. Some antihypertensive drugs used in pregnancy may improve the cellular interaction between trophoblast and endothelial cells exposed to TNF-α. Methyldopa, hydralazine, and clonidine reduced sFlt-1 concentration in culture medium, whereas labetalol increased trophoblast integration independently of sFlt-1. Methyldopa increased VEGF concentration. Some pregnancy-related antihypertensives may affect placental vascularization.

Three-dimensional power Doppler indices of preeclamptic placentas correlated to umbilical artery Doppler and albuminuria

Purpose: To obtain three-dimensional power Doppler (3DPD) indices of placenta in pregnancies complicated with preeclampsia compared to normal pregnancies and correlated to umbilical artery Doppler and albuminuria.Methods: A case-control study was conducted at Ain Shams University Maternity Hospital. Evaluation of placental vascular indices, vascularization index (VI), flow index (FI) and vascularization flow index (VFI), was done using 3DPD in 80 preeclampsia pregnancies compared to 80 normal controls.Results: 3DPD indices (VI, FI and VFI) of preeclampsia cases revealed lower values than controls (p < 0.001). There was a statistical inverse correlation between albuminuria versus VI (p < 0.05) and a statistical inverse correlation was found between VI, FI and VFI versus umbilical artery RI.Conclusion: 3DPD indices of placental vasculature revealed lower values in preeclamptic pregnancies than normal pregnancies. Further studies are needed to discuss the possible role of 3DPD in predicting preeclampsia.

Novel placental ultrasound assessment: Potential role in pre-gestational diabetic pregnancy

ObjectivesManagement of women with pre-gestational diabetes continues to be challenging for clinicians. This study aims to determine if 3D power Doppler (3DPD) analysis of placental volume and flow, and calculation of placental calcification using a novel software method, differ between pregnancies with type 1 or type 2 diabetes and normal controls, and if there is a relationship between these ultrasound placental parameters and clinical measures in diabetics. MethodsThis was a prospective cohort study of 50 women with diabetes and 250 controls (12–40 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental calcification was calculated by computer analysis. Results in diabetics were compared with control values, and correlated with early pregnancy HbA1c, Doppler results and placental histology. ResultsPlacental calcification and volume increased with advancing gestation in pre-gestational diabetic placentae. Volume was also found to be significantly higher than in normal placentae. VI and VFI were significantly lower in diabetic pregnancies between 35 and 40 weeks gestation. A strong relationship was seen between a larger placental volume and both increasing umbilical artery pulsatility index and decreasing middle cerebral artery pulsatility index. FI was significantly lower in cases which had a booking HbA1c level ≥6.5%. Ultrasound assessed placental calcification was reduced with a histology finding of delayed villous maturation. No other correlation with placental histology was found. ConclusionsThis study shows a potential role for 3D placental evaluation, and computer analysis of calcification, in monitoring pre-gestational diabetic pregnancies.

Three‐Dimensional Sonographic Assessment of Placental Volume and Vascularization in Pregnancies Complicated by Hypertensive Disorders

The purpose of this study was to evaluate the association between placental volumes, placental vascularity, and hypertensive disorders in pregnancy. A prospective case-control study was conducted between April 2011 and July 2012. Placental volumes and vascularity were evaluated by 3-dimensional sonographic, 3-dimensional power Doppler histographic, and 2-dimensional color Doppler studies. Pregnant women were classified as normotensive or hypertensive and stratified by the nature of their hypertensive disorders. The following variables were evaluated: observed-to-expected placental volume ratio, placental volume-to-estimated fetal weight ratio, placental vascular indices, and pulsatility indices of the right and left uterine and umbilical arteries. Sixty-six healthy pregnant women and 62 pregnant women with hypertensive disorders were evaluated (matched by maternal age, gestational age at sonography, and parity). Placental volumes were not reduced in pregnancy in women with hypertensive disorders (P > .05). Conversely, reduced placental vascularization indices (vascularization index and vascularization-flow index) were observed in pregnancies complicated by hypertensive disorders (P < .01; P < .01), especially in patients with superimposed preeclampsia (P = .04; P = .02). A weak correlation was observed between placental volumes, placental vascular indices, and Doppler studies of the uterine and umbilical arteries. Pregnancies complicated by hypertensive disorders are associated with reduced placental vascularity but not with reduced placental volumes. These findings are independent of changes in uterine artery Doppler studies. Future studies of the prediction of preeclampsia may focus on placental vascularity in combination with results of Doppler studies of the uterine arteries.

Analysis of placental vascularization in a pharmacological rabbit model of IUGR induced by l-NAME, a nitric oxide synthase inhibitor

ObjectivesWe have previously validated the use of l-nitro-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor, to induce placental hypoperfusion in a rabbit model. Here, the effects of l-NAME on placental vascularization were explored. Transplacental transfer of l-NAME and/or its active metabolite, NG-nitro-l-arginine (L-NOARG), was evaluated. Methods25 pregnant female rabbits were allocated on day 24 to one of 5 groups: l-NAME groups (31.35, 62.5, 125 and 250 mg/kg/day) or Control group (C). On Day 28, the labyrinthine area was analyzed for stereology and gene expression. l-NAME and L-NOARG were quantified in maternal and fetal blood. ResultsThe volume density of fetal vessels was significantly decreased in l-NAME (including 62.5–250 mg/kg/day which induced an IUGR) compared to C groups. l-NAME induced an increase of the volume and surface density of the maternal blood space. The trophoblast volume density remained unchanged as well as the surface density of fetal vessels. Relative expression of eNOS, VEGFA, VEGFR-1 and VEGFR-2 in placentas was not affected by 125 mg/kg/day l-NAME treatment, whereas IGF-2 expression was significantly increased in this l-NAME group compared to C. l-NAME was not detected in maternal nor fetal plasma. In contrast, fetal to maternal L-NOARG ratio was 100% in all l-NAME groups. ConclusionThese data demonstrate that l-NAME induced placental hypovascularization. The active L-NOARG metabolite is found in maternal and fetal plasma at similar concentrations. This could impact the fetal growth and reduces the interest of this model to study fetal outcomes of placental hypoperfusion.

Placental development during early pregnancy in sheep: effects of embryo origin on vascularization

Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from NAT (NAT-ET), or IVF or in vitro activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared with NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM) and for NAT-ET, IVF, and IVA in CAR. In FM, mRNA expression was decreased (P<0.01-0.08) in NAT-ET, IVF, and IVA compared with NAT for vascular endothelial growth factor (VEGF) and its receptor FLT1, placental growth factor (PGF), neuropilin 1 (NP1) and NP2, angiopoietin 1 (ANGPT1) and ANGPT2, endothelial nitric oxide synthase 3 (NOS3), hypoxia-inducible factor 1A (HIF1A), fibroblast growth factor 2 (FGF2), and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01-0.05) in NAT-ET, IVF, and IVA compared with NAT for VEGF, FLT1, PGF, ANGPT1, and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF, and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development.

3D Power Doppler ultrasound and computerised placental assessment in normal pregnancy

BackgroundIn recent years there have been significant developments in the use of 3D Power Doppler (3DPD) imaging and quantitative 3DPD histogram analysis to estimate both placental volume and intra-placental vasculature. This study aims to determine if placental volume, vascularisation and blood flow are correlated with gestational age in normal pregnancy. It also examines whether or not a new software method for analysis of percentage calcification (the ‘placentometer’) correlates well with gestation. Material and methodThis was a prospective cohort study of 250 women with normal pregnancies (12 + 6 to 39 + 5 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental volume (calculated at 35–40 weeks gestation), was correlated with birth weight. Following each scan the percentage of calcification was also calculated using the placentometer. ResultsPlacental volume correlated significantly with gestational age: 66.676 + 0.623 × GA (P < 0.001). No significant change with gestation was noted in VI, FI and VFI (VI: P = 0.199, FI: P = 0.299, VFI: P = 0.557). Software analysis of the percentage of calcification, demonstrated the expected increase in calcification as gestation increased: −4.605 + 0.032 × GA (P < 0.001). From 35 to 40 weeks gestation volume was related to birth weight (P < 0.01). ConclusionThis study shows that in normal low-risk pregnancy placental volume increases with gestational age, whereas vascularisation and blood flow are independent of gestation. Placental volume in late pregnancy is related to birth weight. Software analysis of the percentage of calcification demonstrates an increase with advancing gestation.

Effect of pregestational diabetes mellitus on first trimester placental characteristics: Three-dimensional placental volume and power Doppler indices

ObjectiveTo investigate whether pregestational diabetes mellitus (DM) induces changes in vascular placental development detectable at first trimester. MethodsThis was a prospective case–control study in 69 women with pregestational DM and 94 controls undergoing first-trimester combined screening for aneuploidies. Maternal characteristics, fetal nuchal translucency thickness, maternal serum pregnancy-associated plasma protein A (PAPP-A) and free β human chorionic gonadotrophin (β-hCG) were evaluated. Three-dimensional ultrasound was used to measure placental volume and three dimensional power Doppler (3D-PD) placental vascular indices including: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Pregnancy-associated hypertensive complications (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women and the group of diabetic women without PAHC were compared separately with the control group. Results3D-PD placental vascular indexes were significantly lower in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04). These differences remained on excluding cases with PAHC in the DM group. No differences were found in placental volumes between the DM group and controls. Serum PAPP-A levels were also lower in diabetic women (p < 0.02) and negatively correlated with the degree of maternal metabolic control at first trimester. ConclusionsPregestational DM induces demonstrable alterations in first trimester placental development, with significantly reduced placental vascularization indices and PAPP-A values. This effect is independent of the later development of PAHC.

Activation of the CXCL12/CXCR4 signaling axis may drive vascularization of the ovine placenta

Early pregnancy, when most embryonic losses occur, is a critical period in which vital placental vascularization is established. Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis, and factors that regulate VEGF function, expression, or both may ultimately affect vascularization. Activation of the C-X-C chemokine receptor type 4 (CXCR4) by its cognate ligand, C-X-C chemokine ligand 12 (CXCL12), increases VEGF synthesis and secretion, which in turn stimulates CXCL12 and CXCR4 production and this synergistic regulation may influence placental vascularization. We hypothesized that expression of CXCL12, CXCR4, select angiogenic factors, and their receptors would increase in placental tissues during early pregnancy and that treatment of ovine trophectoderm cells with CXCL12 would increase production of angiogenic factors. To test this hypothesis, maternal caruncle (CAR) and fetal extraembryonic membrane (FM) tissues were collected on days 18, 20, 22, 25, 26, and 30 of pregnancy and on day 10 of the estrous cycle (control, NP) to determine relative mRNA or protein expression of CXCL12 and CXCR4 and selected angiogenic factors. In CAR, expression of mRNA for CXCR4 increased on day 18, 20, 22, and 25 and CXCL12 increased on day 18 and 20 compared with NP ewes. CXCL12 protein followed a similar pattern in CAR tissue, with greater levels on day 20 than in NP tissue. Greater levels of fibroblast growth factor 2 (FGF2) mRNA was observed in CAR on day 20 of gestation than on day 30. In FM, CXCL12, CXCR4, angiopoietin 1, VEGF, and VEGF receptor 1 were enhanced with advancing pregnancy, whereas FGF2 and kinase insert domain receptor (or VEGF receptor 2) peaked on day 25. An increase in protein levels occurred on day 25 compared with day 20 in FM for CXCL12 and CXCR4, as well as a similar tendency for FGF2 protein. Both CXCL12 and CXCR4 are specifically localized to trophoblast cells and to the uterine luminal and glandular epithelium. Treatment of ovine trophectoderm cells with CXCL12 increased mRNA expression for VEGF and FGF2. The relationship between VEGF, FGF2, and the CXCL12/CXCR4 signaling underscores the potential role for this chemokine axis in driving placentation.

826: Membrane proteomic study of the VEGF receptor-2 network in the fetal compartment of human placentas near term

Identify proteins that co-immunoprecipitate (coIP) with VEGFR-2 (KDR) and by their association could affect its signal transduction pathway that regulates placental vascularization and fetal growth. Since KDR synthesizes dinucleoside polyphosphates (Jankowski V. et al.) which activate purinergic receptor P2Y2 known to regulate vasculogenesis, vascular tone and inflammatory responses, we sought to test if P2Y2 coIP with KDR.

Intrauterine growth restriction is associated with strong alterations in placental structure and function in horses

In equids, placentation is diffuse and the nutrient supply to the fetus is determined by uterine size, which is correlated to maternal size and parity. That the size of the mare affects fetal development has previously been shown by embryo transfer (ET) between Ponies and Thoroughbreds [Allen WR, et al; Reproduction 2002;123:445-53.]. We enhanced or restricted fetal growth through ET using Pony (P), Saddlebred (S) and Draft (D) horses and investigated placental morphology, histology and function at term. Control pregnancies of P-P (n1⁄421), S-S (n1⁄428) and D-D (n1⁄48) were obtained by artificial insemination. Enhanced and restricted pregnancies were obtained by transferring P (P-D, n1⁄46) and S embryos (S-D, n1⁄48) into D mares or S embryos into P mares (S-P, n1⁄46), respectively. Placental weight and gross surface area were recorded at delivery. Samples were collected for stereology (quantitative histology) and RT-qPCR analysis of expression of genes involved in placental growth, vascularization and nutrient transport. Statistical analysis of data was performed by Kruskal-Wallis with Dunn’s posthoc test. Data are expressed as means SEM. Mean placental weight and gross surface area were higher in S-S and in D-D compared to P-P (p<0.05) whereas S-S and D-D were not different (4.6 0.17kg and 8046 176.1cm2 in S-S versus 4.9 0.41kg and 9229 596.2cm2 in D-D versus 2.5 0.14kg and 2940 111.7cm2 in P-P for placental weight and surface, respectively). No histological changes were observed among controls, but most genes had their expression decreased in P-P compared to S-S and D-D. P-D foals had a