Placental Blood Flow Research Articles

Assessment of the development of the central nervous system in fetuses with fetal growth restriction.

To evaluate the development of the central nervous system in fetuses with fetal Growth Restriction. A total of 146 pregnant women who underwent prenatal ultrasonography in Cangzhou People's Hospital from January 2022 to May 2024 were selected, all with singleton pregnancies. Among them, 73 fetuses were in the fetal growth restriction group, with ages ranging from 20 to 33 + 6weeks. The indicators for evaluating the cerebral sulci included the depth and angle of the parietooccipital sulci, the width and depth of the sylvian fissure, the width of the uncovered insula, uncover insular ratio, the depth of the calcarine sulci, and the head circumference. The hemodynamic indicators comprised the ratio of the umbilical artery resistance index, the umbilical artery pulse index, the middle cerebral artery resistance index, the middle cerebral artery pulse index, and the cerebral placental blood flow pulse index. The above parameters were analyzed statistically. In this study, the depth of the parietooccipital sulci, the depth of the calcarine sulci, and the width of the sylvian fissure were smaller in the fetal growth restriction group than those in the control group, and the angle of the parietooccipital sulci and the width of the uncovered insula were larger than those in the control group (all P < 0.05). The fetal middle cerebral artery resistance index, middle cerebral artery pulsation index and cerebroplacental pulsation ratio in the FGR group were lower than those in the control group (all P < 0.05). The development of the cerebral cortex in FGR fetuses is slower than that in normal fetuses, and the alteration of fetal hemodynamics might be one of the reasons for the delayed development of the cerebral cortex in FGR fetuses.

Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome

AimsSome patients with Obstetric Antiphospholipid Syndrome (OAPS) still experience miscarriage and placental dysfunction after routine treatment, which is related to an abnormal increase in neutrophil extracellular traps (NETs). The labeling of statins has been revised to remove the contraindication for use during pregnancy. Our aim is to investigate the effect of Simvastatin on pregnancy outcomes in OAPS and its correlation mechanisms with NETs. Main methodsThe effect of Simvastatin on pregnancy outcomes was observed. The effect of simvastatin on the function and apoptosis of neutrophils has evaluated. The effect of Simvastatin to NETs and the changes in oxidative stress levels were observed. Different groups of NETs were extracted to intervene the HTR8-Svneo.RNA-seq analysis of the mechanism of which Simvastatin reduces NETs. Seahorse experiment detected the effect of Simvastatin on neutrophil glycolysis levels. Fluorescence co-localization and flow cytometry and Co-IP were used to verify relevant mechanisms. Key findingsIn the OAPS mice, Simvastatin can reduce embryo absorption rate, reshape placental blood flow perfusion. Simultaneously reducing the production of NETs both in vivo and vitro, remolding oxidative stress. Simvastatin can improve neutrophil dysfunction caused by aPL-IgG. The reduction of NETs improved HTR8-Svneo's dysfunction. The intervention of Simvastatin on neutrophils under the stimulation of aPL-IgG showed a signature in glycolytic. The key rate limiting enzyme PKM2 in glycolysis interacts with Cit-H2b and PI3K/AKT signaling pathway. SignificanceOur study providing basic theoretical support for the treatment of OAPS with Simvastatin.

Study protocol for an observational cohort study of heat stress impacts in pregnancy in The Gambia, West Africa

Climate change has resulted in an increase in heat exposure globally. There is strong evidence that this increased heat stress is associated with poor maternal and fetal outcomes, especially in vulnerable populations. However, there remains poor understanding of the biological pathways and mechanisms involved in the impact of heat in pregnancy. This observational cohort study of 764 pregnant participants based in sub-Saharan Africa, a geographical region at risk of extreme heat events, aims to evaluate the physiological and biochemical changes that occur in pregnancy due to heat stress. The key objectives of the study are to 1) map exposure to heat stress in the cohort and understand what environmental, social and community factors increase the risk of extreme heat exposure; 2) assess the impact of heat stress on maternal health, e.g. heat strain, subjective psychological well-being, sleep and activity level; 3) evaluate how heat stress impacts placenta structure and function; 4) determine how chronic heat exposure impacts birth outcomes; and 5) explore the epigenetic changes in the placenta and infant by heat stress exposure per trimester. Pregnant women will be recruited from two distinct regions in The Gambia to exploit the naturally occurring heat gradient across the country. Microclimate mapping of the area of recruitment will give detailed exposure measurements. Participants will be asked to wear a watch-style device at 28- and 35-weeks gestational age to evaluate maternal heart rate, activity and sleep. At the end of the week, an ultrasound scan will be performed to evaluate fetal size and placental blood flow. At delivery, birth outcomes will be recorded and maternal, placental and cord samples taken for epigenetic, biochemical and histological evaluation. Evaluation of neuro-behaviour and final infant samples will be taken at 1 month following birth.

Chronic Hypoxia in an EXTrauterine Environment for Neonatal Development Impairs Lung Development.

Severe fetal hypoxia poses a significant risk to lung development resulting in severe postnatal complications. Existing chronic hypoxia animal models lack the ability to achieve pathologically reduced fetal oxygen without compromising animal development, placental blood flow, or maternal health. Using an established model of isolated chronic hypoxia involving the Extrauterine Environment for Neonatal Development (EXTEND), we are able to investigate the direct impact of fetal hypoxia on lung development. Oxygen delivery to preterm fetal lambs (105-110 days GA) delivered by cesarean section was reduced, and animals were supported on EXTEND through the canalicular or saccular stage of lung development. Fetal lambs in hypoxic conditions showed significant growth restriction compared to their normoxic counterparts. We also observed modest aberrant vascular remodeling in the saccular group after hypoxic conditions with decreased macrovessel numbers, microvascular endothelial cell numbers, and increased peripheral vessel muscularization. In addition, fetal hypoxia resulted in enlarged distal airspaces and decreased septal wall volume. Moreover, there was a reduction in mature SFTPB and processed SFTPC protein expression concomitant with a decrease in AT2 cell number. These findings demonstrate that maternally-independent fetal hypoxia predominantly impacts distal airway development, AT2 cell number, and surfactant production with mild effects on the vasculature.

Growth factor dysregulation and placental dysfunction

The article is devoted to the study of angiogenic and antiangiogenic vascular growth factors in placental dysfunction, which is of great importance in obstetrics and perinatology. The study of growth factors as predictors of the development of placental dysfunction makes it possible to determine in advance the development of many obstetric pathologies, including preeclampsia and fetal growth retardation, which is of great practical importance. The authors conducted an immunological study of pregnant women with placental dysfunction and pregnant women with a physiological pregnancy. Purpose of the study: to study serum growth factors in women with placental dysfunction. We examined 47 pregnant women with a gestation period of 26-40 weeks, with a diagnosis of placental dysfunction, who were under observation in the obstetric department of the city maternity complex No. 3 of the city of Tashkent. The control group consisted of 35 women with a physiological pregnancy. All women underwent an immunological blood test: cellular and humoral immunity, as well as cytokines (VEGF-A, PlGF, sFlt-1, sFlt-1/PlGF) were studied. Based on the results obtained, the authors suggest that an increased level of soluble sFlt-1 and a simultaneous decrease in the levels of VEGF-A and PlGF in pregnant women at 26-40 weeks of gestation may portend the development of pregnancy complications, including preeclampsia and fetal growth restriction, and increase the risk of premature birth. Ddelivery due to impaired placental blood flow and oxygen deficiency for the fetus, lead to deterioration of microcirculation, and insufficient levels of VEGF-A and PlGF can contribute to vascular endothelial dysfunction, which can also contribute to the development of preeclampsia. The studied angiogenic and antiangiogenic vascular growth factors are important indicators and can serve as markers for predicting pregnancy complications for active medical intervention in maintaining the health of both mother and child.

8429 Serotonin Receptor Antagonist Alleviates Vascular Defects Produced by Selective Serotonin Reuptake Inhibitor Treatment During Gestation

Abstract Disclosure: L.P. Agnew: None. R. Domingues: None. A. Weichmann: None. L.L. Hernandez: None. Maternal mental health is critical for both mother and infant and often antidepressant therapy outweighs the potential risks of selective serotonin reuptake inhibitor (SSRI) treatment; however, SSRI use is associated with adverse neonatal outcomes. Preliminary work in our laboratory revealed placental apoptosis in pregnant dams treated with fluoxetine (FLX) and dams genetically deficient for the serotonin transporter gene. We hypothesize that SSRIs decrease placental blood flow, causing apoptosis and organ death via signaling through the serotonin 2A/2C receptors. Pregnant female C57BL6 mice were randomized to be treated daily, via I.P. injection, from E10-17.5 with saline (CON; n=6), 2 mg/kg FLX (n=5), or 2 mg/kg ketanserin plus 2 mg/kg FLX (n=5). On E17.5, using high-resolution ultrasound imaging, we identified the uterine artery, individual umbilical cords, and placental disc blood vessels. We calculated blood pressure, blood volume, blood flow rate, and heart rate in the uterine artery, umbilical cord, and placental disc. FLX (decreased blood volume in the uterine artery compared to ketanserin plus FLX (48.42 ± 18.26, 116.54 ± 45.25; p=0.0077), and decreased average (89.38 ± 31.50) and peak (130.36 ± 39.05) blood velocity in the uterine artery compared to ketanserin plus FLX average (162.76 ± 68.46; p=0.0322) and peak (236.77 ± 92.43; p=0.0242) blood velocity. FLX decreased average (0.04 + 0.02) and peak (0.07 ± 0.04) blood pressure in the uterine artery compared to ketanserin and FLX treated animals average (0.12 ± 0.10; p=0.0634) and peak (0.25 ± 0.19; p=0.0412) blood pressure. Ketanserin plus FLX (391 ± 38.29) decreased heart rate (BPM) in the placental disc compared to untreated controls (450.67 ± 26.08; p=0.0128). In the umbilical cord, ketanserin plus FLX (393 ± 28.25) decreased BPM compared to CON (450.17 ± 29.44; p=0.0078) and compared to FLX treatment alone (437.20 ± 17.28; p=0.0450). FLX treatment of dams during pregnancy reduces blood flow volume, heart rate, and blood flow velocity to the placenta via the uterine artery. The use of ketanserin, an inhibitor of serotonin receptor 2A/2C signaling, in combination with FLX, reduced the effects of FLX on the uterine artery. These data suggest that treatment with ketanserin could be utilized to alleviate the reproductive side effects of antidepressant usage for pregnant mothers while allowing the mother to remain on antidepressants. Future research should further investigate the effects of SSRI and ketanserin on blood flow to the fetus through the umbilical cord. Presentation: 6/2/2024

8429 Serotonin Receptor Antagonist Alleviates Vascular Defects Produced by Selective Serotonin Reuptake Inhibitor Treatment During Gestation

Abstract Disclosure: L.P. Agnew: None. R. Domingues: None. A. Weichmann: None. L.L. Hernandez: None. Maternal mental health is critical for both mother and infant and often antidepressant therapy outweighs the potential risks of selective serotonin reuptake inhibitor (SSRI) treatment; however, SSRI use is associated with adverse neonatal outcomes. Preliminary work in our laboratory revealed placental apoptosis in pregnant dams treated with fluoxetine (FLX) and dams genetically deficient for the serotonin transporter gene. We hypothesize that SSRIs decrease placental blood flow, causing apoptosis and organ death via signaling through the serotonin 2A/2C receptors. Pregnant female C57BL6 mice were randomized to be treated daily, via I.P. injection, from E10-17.5 with saline (CON; n=6), 2 mg/kg FLX (n=5), or 2 mg/kg ketanserin plus 2 mg/kg FLX (n=5). On E17.5, using high-resolution ultrasound imaging, we identified the uterine artery, individual umbilical cords, and placental disc blood vessels. We calculated blood pressure, blood volume, blood flow rate, and heart rate in the uterine artery, umbilical cord, and placental disc. FLX (decreased blood volume in the uterine artery compared to ketanserin plus FLX (48.42 ± 18.26, 116.54 ± 45.25; p=0.0077), and decreased average (89.38 ± 31.50) and peak (130.36 ± 39.05) blood velocity in the uterine artery compared to ketanserin plus FLX average (162.76 ± 68.46; p=0.0322) and peak (236.77 ± 92.43; p=0.0242) blood velocity. FLX decreased average (0.04 + 0.02) and peak (0.07 ± 0.04) blood pressure in the uterine artery compared to ketanserin and FLX treated animals average (0.12 ± 0.10; p=0.0634) and peak (0.25 ± 0.19; p=0.0412) blood pressure. Ketanserin plus FLX (391 ± 38.29) decreased heart rate (BPM) in the placental disc compared to untreated controls (450.67 ± 26.08; p=0.0128). In the umbilical cord, ketanserin plus FLX (393 ± 28.25) decreased BPM compared to CON (450.17 ± 29.44; p=0.0078) and compared to FLX treatment alone (437.20 ± 17.28; p=0.0450). FLX treatment of dams during pregnancy reduces blood flow volume, heart rate, and blood flow velocity to the placenta via the uterine artery. The use of ketanserin, an inhibitor of serotonin receptor 2A/2C signaling, in combination with FLX, reduced the effects of FLX on the uterine artery. These data suggest that treatment with ketanserin could be utilized to alleviate the reproductive side effects of antidepressant usage for pregnant mothers while allowing the mother to remain on antidepressants. Future research should further investigate the effects of SSRI and ketanserin on blood flow to the fetus through the umbilical cord. Presentation: 6/2/2024

Hypoglycaemia in screening oral glucose tolerance test in pregnancy with low birth weight fetus.

Maternal hypoglycemia, a condition characterized by lower than normal blood glucose levels in pregnant women, has been increasingly associated with adverse pregnancy outcomes, including low birth weight (LBW) in neonates. LBW, defined as a birth weight of less than 2500 g, can result from various factors, including maternal nutrition, health status, and metabolic conditions like hypoglycemia. Maternal hypoglycemia may affect fetal growth by altering the supply of essential nutrients and oxygen to the fetus, leading to restricted fetal development and growth. This condition poses significant risks not only during pregnancy but also for the long-term health of the child, increasing the likelihood of developmental delays, health issues, and chronic conditions later in life. Research in this area has focused on understanding the mechanisms through which maternal hypoglycemia influences fetal development, with studies suggesting that alterations in placental blood flow and nutrient transport, as well as direct effects on fetal insulin levels and metabolism, may play a role. Given the potential impact of maternal hypoglycemia on neonatal health outcomes, early detection and management are crucial to minimize risks for LBW and its associated complications. Further investigations are needed to fully elucidate the complex interactions between maternal glucose levels and fetal growth, as well as to develop targeted interventions to support the health of both mother and child. Understanding these relationships is vital for improving prenatal care and outcomes for pregnancies complicated by hypoglycemia.

A Study to Assess the Effectiveness of Structured Teaching Programme on Knowledge Regarding Effect of Caffeinated Food on Fetus among Primigravida Women in Selected Hospitals, Bangalore

A Study was conducted to assess the effectiveness of structured teaching program on knowledge regarding effect of caffeinated food on fetus among primary gravida women in selected hospital, Bangalore. Quasi experimental one group pre-test post-test design (O1 X O2) was adopted for this study. Purposive sampling technique was used to select 60 samples. Structured teaching program was implemented to the primary gravida women for 21 days. Post-test was done after a week of intervention. The data were gathered and analyzed by descriptive and inferential statistical method. The findings revealed that During pretest 17(28.33%) and 43(71.66%) of the samples had inadequate and moderate knowledge respectively. During post-test 48(80%) and 05(8.33%) and 7(11.66%) of samples had moderate, inadequate and adequate knowledge. The paired ‘t’ value for knowledge was 5.25 Which was greater than the table value 1.67 at P ≤ 0.05 level indicating the difference in mean was true difference and structured teaching program was effective in increasing knowledge regarding caffeinated food on fetus among primigravida women. Significant association was found on only family’s annual income hence research hypothesis are retained. Eating a well-balanced diet is crucial for a pregnant women and caffeine has been shown to increase epinephrine concentrations in mother and fetus resulting in decreased placental blood flow and hypoxia.

A genetically small fetus impairs placental adaptations near term.

The placenta is a gatekeeper between the mother and fetus, adapting its structure and functions to support optimal fetal growth. Studies exploring adaptations of placentae that support the development of genetically small fetuses are lacking. Here, using a mouse model of impaired fetal growth, achieved by deleting insulin-like growth factor 2 (Igf2) in the epiblast, we assessed placental nutrient transfer and umbilical artery (UA) blood flow during late gestation. At embryonic day (E) 15.5, we observed a decline in the trans-placental flux of glucose and system A amino acids (by using 3H-MeG and 14C-MeAIB), proportionate to the diminished fetal size, whereas UA blood flow was normal. However, at E18.5, the trans-placental flux of both tracers was disproportionately decreased and accompanied by blunted UA blood flow. Feto-placental growth and nutrient transfer were more impaired in female conceptuses. Thus, reducing the fetal genetic demand for growth impairs the adaptations in placental blood flow and nutrient transport that normally support the fast fetal growth during late gestation. These findings have important implications for our understanding of the pathophysiology of pregnancies afflicted by fetal growth restriction.

Efficacy of Combination Therapy Using Crystalloid, Colloid and Ephedrine in Prevention of Post Spinal Hypotension at Cesarean Delivery

Abstract Background Spinal anesthesia is the preferred method for elective cesarean sections due to considerable risks regarding airway management associated with physiological changes of pregnancy. Hypotension is reported to occur in up to 80% of spinal anesthesia cases, it can lead to serious maternal complications as well as impairment of the uterine and placental blood flow. Many approaches have been investigated to prevent spinal hypotension, e.g., fluid loading, vasopressors, or both. Objective To determine the most effective strategy to decrease the incidence and severity of post spinal hypotension by comparing three different combination therapies using crystalloid, colloid and ephedrine at cesarean delivery. Patients and Methods After obtaining approval from the Research Ethical Committee of Faculty of Medicine, Ain Shams University, and written informed consent from all parturients this study was conducted in the operating theatres of Ain Shams Obstetric and Gynecology University Hospitals. Results In our study we found that a combination of an ephedrine infusion at 1.25 mg, minute with a crystalloid co-load was more effective in the prevention of hypotension. Conclusion Employing all mentioned combination treatments reduced the rate of hypotension occurrence following spinal anesthesia in parturients undergoing cesarean delivery. The most effective method was administration of crystalloid coloading plus ephedrine infusion.

Assessment of Red Blood Cell Aggregation in Preeclampsia by Microfluidic Image Flow Analysis-Impact of Oxidative Stress on Disease Severity.

Preeclampsia (PE) is a hypertensive disease characterized by proteinuria, endothelial dysfunction, and placental hypoxia. Reduced placental blood flow causes changes in red blood cell (RBC) rheological characteristics. Herein, we used microfluidics techniques and new image flow analysis to evaluate RBC aggregation in preeclamptic and normotensive pregnant women. The results demonstrate that RBC aggregation depends on the disease severity and was higher in patients with preterm birth and low birth weight. The RBC aggregation indices (EAI) at low shear rates were higher for non-severe (0.107 ± 0.01) and severe PE (0.149 ± 0.05) versus controls (0.085 ± 0.01; p < 0.05). The significantly more undispersed RBC aggregates were found at high shear rates for non-severe (18.1 ± 5.5) and severe PE (25.7 ± 5.8) versus controls (14.4 ± 4.1; p < 0.05). The model experiment with in-vitro-induced oxidative stress in RBCs demonstrated that the elevated aggregation in PE RBCs can be partially due to the effect of oxidation. The results revealed that RBCs from PE patients become significantly more adhesive, forming large, branched aggregates at a low shear rate. Significantly more undispersed RBC aggregates at high shear rates indicate the formation of stable RBC clusters, drastically more pronounced in patients with severe PE. Our findings demonstrate that altered RBC aggregation contributes to preeclampsia severity.

Integrating Ultrasound and Histopathological Analysis to Investigate Placental Abnormalities and Blood Flow in Uteroplacental Insufficiency: A Comprehensive Study

Integrating Ultrasound and Histopathological Analysis to Investigate Placental Abnormalities and Blood Flow in Uteroplacental Insufficiency: A Comprehensive Study

Maternal physical activity and sitting time and its association with placental morphology and blood flow during gestation: Findings from the Queensland Family Cohort study

ObjectivesAntenatal exercise is associated with placental morphological alterations, however research in this area is limited. Given the emphasis on the beneficial effects of antenatal exercise, it is important to understand its effect on placental function and the relationship to foetal development. The aim of this study was to investigate the association between physical activity, sitting time, and placental outcomes measured during gestation. DesignProspective cohort study. MethodsPregnant women in the Queensland Family Cohort study self-reported physical activity at 24 and 36 weeks of gestation (n = 203) and were categorised into physical activity volume groups of nil–low (0–<500 metabolic equivalent of task·minutes/week), moderate (500–<1000 metabolic equivalent of task·minutes/week), or high-volume activity (≥1000 metabolic equivalent of task·minutes/week). Participants reported average daily sitting time, whereby excessive sitting time was considered as ≥8h/day. Placental stiffness, thickness, and uteroplacental blood flow resistance were measured by ultrasound imaging at each timepoint. ResultsPhysical activity volume was not associated with changes to placental morphometrics or uteroplacental blood flow resistance at 24 or 36 weeks of gestation. Excessive sitting time at 36 weeks was associated with greater placental stiffness (p = 0.046), and a lower umbilical artery pulsatility index (p = 0.001). ConclusionsPlacental tissue stiffness and umbilical artery resistance were altered in late gestation with higher maternal sitting time but not with physical activity volume. Overall, excessive sitting time may be a risk for suboptimal placental function and could be an important focus for antenatal care.

Characterization of placentome vascular perfusion in relation to pregnancy associated glycoproteins throughout gestation in pregnant beef heifers

During pregnancy, blood flow to the uterus changes to support fetal demand. Placentomes serve as vascular attachment sites on the placenta for exchange of gases, nutrients, and metabolic products. Non-invasive methods of ultrasonography and biomarkers have been described to assess placental health and fetal viability. Pregnancy associated glycoproteins (PAGs) are produced by the ruminant placenta and are detected in maternal circulation. In cattle, changes in circulating PAG concentrations are associated with embryonic and fetal outcomes. The objective of this study was to determine the association between placentome blood perfusion and circulating PAG concentrations as they relate to the health of the developing fetus. We hypothesized that placentome perfusion and PAG concentration will be positively correlated and associated with neonatal outcome. A prospective, observational study was designed using 26 pregnant, nulliparous, Angus heifers in which PAG concentration and placentome blood perfusion were assessed throughout gestation, with assessment of calving characteristics following parturition. Placentome blood perfusion was visualized at 30-day intervals via transrectal Doppler ultrasonography with power flow function. Ultrasound images were analyzed using ImageJ software to determine the percent area of perfusion and integrated pixel densities. Venous blood was collected and PAG concentrations were determined via serum PAG enzyme-linked immunoassay. Mean placentome blood perfusion increased as gestation advanced. PAG concentrations demonstrated the expected temporal trend, increasing with gestation length, and were positively linearly correlated with placentome perfusion (P < 0.0001). The relationship identified between circulating PAG concentration and placentome blood perfusion suggests the use of transrectal power flow Doppler ultrasonography as a noninvasive technique to determine placental blood flow morphometrics to assess conceptus wellbeing throughout pregnancy.

Cotyledon-Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast-Enhanced MRI.

Recently, dynamic contrast-enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions. To measure cotyledon-specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury. Prospective animal model. Placental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 μg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165). 3 T, T1-weighted spoiled gradient echo sequence (product sequence, DISCO). Source images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP-1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals. Wilcoxon rank sum test, significance level P < 0.05. No motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute-1. Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel-treated (single dose) animal and both Tisseelx3 (triple dose) animals. This study demonstrates the feasibility of cotyledon-specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol-enhanced DCE MRI. NA TECHNICAL EFFICACY: Stage 2.

Placental size at gestational week 27 and 37: The associations with pulsatility index in the uterine and the fetal-placental arteries

IntroductionFetal growth restriction is known to be related to decreased fetal and placental blood flow. It is not known, however, whether placental size is related to fetal and placental blood flow. We studied the correlations of intrauterine placental volume and placental-fetal-ratio with pulsatility index (PI) in the uterine arteries, fetal middle cerebral artery, and umbilical artery. MethodsWe followed a convenience sample of 104 singleton pregnancies, and we measured placental and fetal volumes using magnetic resonance imaging (MRI) at gestational week 27 and 37 (n = 89). Pulsatility index (PI) was measured using Doppler ultrasound. We calculated cerebroplacental ratio as fetal middle cerebral artery PI/umbilical artery PI and placental-fetal-ratio as placental volume (cm3)/fetal volume (cm3). ResultsAt gestational week 27, placental volume was negatively correlated with uterine artery PI (r = −0.237, p = 0.015, Pearson's correlation coefficient), and positively correlated with fetal middle cerebral artery PI (r = 0.247, p = 0.012) and cerebroplacental ratio (r = 0.208, p = 0.035). Corresponding correlations for placental-fetal-ratio were −0.273 (p = 0.005), 0.233 (p = 0.018) and 0.183 (p = 0.064). Umbilical artery PI was not correlated with placental volume. At gestational week 37, we found weaker and no significant correlations between placental volume and the pulsatility indices. ConclusionsOur results suggest that placental size is correlated with placental and fetal blood flow at gestational week 27.

Intra-uterine programming of future fertility.

The developmental origins of health and disease (DOHaD) shows that a relationship exists between parental environment at large, foeto-placental development and the risk for the offspring to develop non-transmittable disease(s) in adulthood. This concept has been validated in both humans and livestock. In mammals, after fertilization and time spent free in the maternal reproductive tract, the embryo develops a placenta that, in close relationship with maternal endometrium, is the organ responsible for exchanges between dam and foetus. Any modification of the maternal environment can lead to adaptive mechanisms affecting placental morphology, blood flow, foetal-maternal exchanges (transporters) and/or endocrine function, ultimately modifying placental efficiency. Among deleterious environments, undernutrition, protein restriction, overnutrition, micronutrient deficiencies and food contaminants can be outlined. When placental adaptive capacities become insufficient, foetal growth and organ formation is no longer optimal, including foetal gonadal formation and maturation, which can affect subsequent offspring fertility. Since epigenetic mechanisms have been shown to be key to foetal programming, epigenetic modifications of the gametes may also occur, leading to inter-generational effects. After briefly describing normal gonadal development in domestic species and inter-species differences, this review highlights the current knowledge on intra-uterine programming of offspring fertility with a focus on domestic animals and underlines the importance to assess transgenerational effects on offspring fertility at a time when new breeding systems are developed to face the current climate changes.

284 Supranutritional Mineral Supplementation During Pregnancy Alters Placental Blood Flow and Calf Mineral Concentrations

Abstract Fetal development is dependent on maternal nutrient status, and the maternal-fetal connection is mediated by the placenta. There are well-established nutrient requirements for gestating cattle aimed at promoting the health of dam and fetus; however, there is limited information on the impact of supranutritional nutrient availability on placental function and calf development. This study evaluated the effect of supranutritional mineral administration during gestation on uterine artery blood flow and calf mineral status. Angus and SimAngus cows (n = 52) were bred via artificial insemination. At d 60 of gestation, cows were assigned to treatment groups; an injectable group (INJ, n = 26) receiving a single subcutaneous mineral injection and access to free-choice trace minerals and a control group (CON; n = 26) having access to free-choice trace minerals. Liver mineral content was analyzed in a subset of cows (CON n = 10; INJ n = 6) at d 60 and 209 ± 1 of gestation. At d 139.5 ± 0.5 and 209 ±1 of gestation, uterine artery measurements were collected using Color Doppler ultrasonography. Placental cotyledons, liver tissue, and blood samples were collected from a subset of animals at calving (n = 11; CON, n = 5; INJ, n = 6). Analysis revealed a TRT*day interaction at d 139.5 ± 0.5 for circulating Co concentrations which were greater (P = 0.05) and Se tended to be greater in INJ cows (P = 0.09) compared with CON cows. Circulating Zn concentrations tended to be decreased at d 209 ± 1 (P = 0.06) in INJ cows compared with the CON cows. Circulating Cu tended to be increased (P = 0.09) and Mn was decreased (P = 0.04) in INJ cows throughout the study. Hepatic Fe concentrations were decreased in INJ cows (P = 0.01) at d 209 ± 1. At d 139.5 ± 0.5, non-gravid uterine artery area, diameter, and circumference were increased in the INJ cows (P &amp;lt; 0.006 ). Additionally, pulsatility index of the gravid uterine artery tended to be increased (P = 0.09) in the INJ cows. Blood and liver samples were collected from calves (CON n = 24; INJ n = 26) at 4 to 8 d post-calving to assess mineral concentrations. INJ calves had greater liver Se (P = 0.001), decreased Fe (P = 0.04), and tended to have increased Zn (P = 0.09) and Mn (P = 0.08) concentrations compared with CON calves. Finally, INJ calves tended to have greater serum Se concentrations (P = 0.09) compared with CON calves. Trace minerals have roles in immune function and impact overall calf health. These results indicate that supranutritional trace mineral administration during early gestation alters placental blood flow and improves calf mineral availability. This supplementation protocol may provide the opportunity to improve the health of future calf crops.

87 Improving Pig Livability Before, During, and After Parturition

Abstract Nearly a quarter of piglets are lost from farrowing to weaning, with stillbirths representing about 7.5% and preweaning mortality contributing another 15.7% in North America (Pigchamp, Metafarm). This averages to a loss of 7.37 pigs per sow per year resulting in significant economic loss and animal welfare concerns. Main contributors of low piglet survivability include poor sow body condition at farrowing, long farrowing duration, piglet asphyxiation, insufficient colostrum consumption, and health challenges. Piglet livability can be improved through nutrition and management solutions before, during, and after parturition. In this context three main strategies have been shown to be effective: 1) managing sow body composition, 2) improving fetal oxygen and nutrient supply via the nitric oxide pathway, and 3) improving piglet health through functional ingredients in the diet of the sow. Highly prolific sows (&amp;gt; 16 born alive) lose both backfat and muscle during the later stages of gestation. Additionally, loin depth loss is more detrimental for piglet survival compared with backfat loss. Sows with the highest stillborn (&amp;gt; 2 per litter) lose the most loin muscle depth regardless of genetics. A solution to reduce this effect and improve piglet survivability is a two-phase gestation feeding with more amino acids in late gestation. Average farrowing duration of a highly prolific sow is 300 minutes and increasing with larger litters. To make things worse, most sows are going through farrowing without food and/or drink. Nutrients and energy supply to sow are critical for shorting farrowing duration and piglet survivability. Compared with pigs that died before weaning, surviving pigs at weaning have greater blood oxygen and less carbon dioxide and lactate at birth. Nitric oxide boosting technologies have been used widely to enhance athletic performance and increase endurance. This vasodilative effect of nitric oxide can be used similarly in sows to increased placental blood flow and thus oxygen and nutrient supply to fetuses. This reduces the risk of asphyxiation and therefore can increase piglet vitality at birth and decreases stillbirth and pre-weaning mortality. Post-parturition health challenge poses a large risk to piglet survivability. Functional feed ingredients, such as botanicals, are a potential solution to improve piglet health and resilience to challenging conditions. Some botanicals can pass through placenta and milk to supply piglets. Milk from sows fed specific botanicals has been shown to improve inhibitory activity against Bacillus subtilis and Staphylococcus aureus. Some specific botanicals can improve sow and piglet antioxidant status, and piglet gut health. In conclusion, managing sow body condition, nitric oxide pathway stimulation, and functional sow diets are effective ways to improve piglet survivability in challenging environments.