Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes

Dietary melatonin supplementation during mid- to late-gestation increased umbilical artery blood flow and caused disproportionate fetal growth. This melatonin-induced increase in umbilical artery blood flow may alter nutrient availability to the fetus, which may lead to alterations in fetal size. The objectives of the current experiment were to determine amino acid (AA) and glucose concentrations as well as AA and glucose flux across the uteroplacenta using a mid- to late-gestation model of intrauterine growth restriction supplemented with dietary melatonin as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% (adequate; ADQ) or 60% (restricted; RES) of nutrient requirements. On day 130 of gestation, uterine and umbilical blood flows were determined via Doppler ultrasonography during a non-survival surgery. Blood samples were collected under general anesthesia from the maternal saphenous artery, gravid uterine vein, umbilical artery, and umbilical vein for AA analysis and glucose. Total α-AA concentrations in maternal artery and gravid uterine vein were decreased (P < 0.05) in RES v. ADQ fed ewes. Maternal arterial − venous difference in total α-AA was increased (P ⩽ 0.01) in RES v. ADQ fed ewes, while total uterine α-AA flux was not different (P > 0.40) across all treatment groups. Fetal venous − arterial difference in total α-AA as well as uteroplacental flux of total α-AA were decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Maternal concentrations and uterine flux of branched-chain AA (BCAA) were not different across all treatment groups; however, fetal uptake of BCAA was decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Uterine uptake of glucose was not different (P ⩾ 0.08) across all treatment groups, while uteroplacental uptake of glucose was increased (P ⩽ 0.05) in RES v. ADQ ewes. In conclusion, maternal nutrient restriction increased maternal arterial − venous difference in total α-AA, while total uterine α-AA flux was unaffected by maternal nutrient restriction. Melatonin supplementation did not impact maternal serum concentrations or uterine flux of glucose or AA; however, melatonin did improve fetal BCAA uptake during maternal nutrient restriction.     

Placental Glucose Transfer: A Human In Vivo Study

ObjectivesThe placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply) determines the fetal venous-arterial glucose difference (reflecting fetal consumption).MethodsCross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein) and outgoing vessels (uterine vein and umbilical artery).ResultsThere were significant mean (SD) uteroplacental arterio-venous 0.29 (0.23) mmol/L and fetal venous-arterial 0.38 (0.31) mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42) mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001), but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001) and the glucose concentration in the umbilical artery (r = −0.45, p = 0.004). Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001), but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.ConclusionsWe did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly influenced by the fetal venous-arterial difference and not merely dependent on maternal glucose concentration or the arterio-venous difference on the maternal side of the placenta.     

Immunoreactive endothelin concentrations in maternal and fetal blood

Immunoreactive-endothelin (ir-ET) concentrations were determined in peripheral maternal blood and in umbilical cord blood just after delivery. The concentrations in both the umbilical artery (2.83 +/- 1.36 pmol/l plasma, Mean +/- SD) and vein (3.37 +/- 1.53 pmol/l) were significantly higher than those found in maternal venous blood (1.43 +/- 1.02 pmol/l). On the other hand, ir-ET levels in maternal blood were not significantly different when compared with those found in non-pregnant women (1.50 +/- 0.83 pmol/l). No significant difference of ir-ET levels between the umbilical artery and vein was observed. A highly significant correlation (r = 0.60, p less than 0.01) of ir-ET levels between the umbilical artery and vein was observed. Also, a significant correlation (r = 0.48, p less than 0.01) between umbilical vein and maternal vein ir-ET levels with a weaker correlation (r = 0.36, p less than 0.05) between umbilical artery and maternal vein ir-ET levels was demonstrated. The present study indicates that ir-ET may be actively secreted in fetal circulation and the plasma levels in maternal and fetal circulation may have a possible relation.     

Regulation of uterine and umbilical amino acid uptakes by maternal amino acid concentrations

We tested the hypothesis that decreased fetal amino acid (AA) supply, produced by maternal hypoaminoacidemia (low AA) during hyperglycemia (HG), is reversible with maternal AA infusion and regulates fetal insulin concentration ([I]). We measured net uterine and umbilical AA uptakes during maternal HG/low AA concentration ([AA]) and after maternal intravenous infusion of a mixed AA solution. After 5 days HG, all maternal [AA] except glycine were decreased >50%, particularly essential [AA] (P < 0.00005). Most fetal [AA] also were decreased, especially branched-chain AA (P < 0.001). Maternal AA infusion increased net uterine uptakes of Val, Leu, Ile, Met, and Ser and net umbilical uptakes of Val, Leu, Ile, Met, Phe, and Arg but did not change net uteroplacental uptake of any AA. Fetal [I] increased 55 +/- 14%, P < 0.001, with correction of fetal [AA], despite the lack of change in fetal glucose concentration. Thus generalized maternal hypoaminoacidemia decreases uterine and umbilical uptakes of primarily the essential AA and decreases fetal branched-chain [AA]. These changes are reversed with correction of maternal [AA], which also increases fetal [I].     

Study of the development of uteroplacental and fetal feline circulation by triplex Doppler

The objective was to evaluate blood flow in fetal and maternal vessels by Triplex Doppler and its association with development of blood vessels during gestation in the domestic cat. Ten queens were examined weekly from 14 to 63 d after mating. Peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI) of uteroplacental, aorta and umbilical fetal arteries and caudal vena cava of the fetus were evaluated. Throughout pregnancy, there was an increase in PSV and EDV in the aorta and umbilical arteries. In the caudal vena cava, there was an increase in PSV, whereas the EDV was constant, with a significant increase on Day 63. Peak systolic velocity and EDV of the uteroplacental artery reduced significantly on Day 63. Resistance index of the umbilical artery progressively decreased. In the aorta, this reduction was detected only on Day 42, with no defined pattern in the caudal vena cava and uteroplacental artery. Pulsatility index of the aorta varied. Although pulsatility increased in the caudal vena cava on Day 35 and remained elevated, pulsatility was significantly reduced in the umbilical artery by Day 63. The pulsatility index of the uteroplacental artery was constant (increased only on Day 63). Triplex Doppler evaluation could be a useful adjunct for prenatal care of pregnant queens, including assessment of vascular gestational development and prediction of gestational age.     

Stimulated cytokine production correlates in umbilical arterial and venous blood at delivery

BACKGROUND: Umbilical venous blood is easy to obtain after delivery, and thus has been commonly used in many studies for cytokine analysis. Our aim was to evaluate whether or not induced cytokine production differs after stimulation in umbilical artery and vein whole blood samples, using two different stimulation protocols. The effect of such stimulation on fetal and maternal blood was also evaluated. METHODS: Blood samples from umbilical artery (UA) and vein (UV), and from the mother were collected from 23 women after delivery at term. Concentrations of cytokines (IL-4, IFN-gamma, IL-6 and TNF-alpha) were measured in plasma and whole blood after PMA/ConA and PMA/ionomycin stimulation. RESULTS: Both in maternal and in fetal samples, cytokine concentrations in unstimulated plasma samples were lower than in stimulated samples, except for IL-4 after PMA/ConA stimulation. UA and UV showed similar, average cytokine levels after stimulation and the correlations were high (r=0.68-0.95). Cytokine concentrations were clearly higher in umbilical blood than in maternal blood after stimulation, but not in plasma. Correlations between maternal and umbilical samples after stimulation were generally low (r<0.41). IFN-gamma was not detectable in unstimulated plasma samples. The production of IL-4 and IFN-gamma was more intense after PMA/ionomycin stimulation than after PMA/ConA stimulation. INTERPRETATION OF THE RESULTS: Concentrations of the cytokines examined are similar in blood from the UA and UV. For IL-4 and IFN-gamma, the stimulant used has a significant effect on the level of cytokine expression, and interestingly, the effect is more pronounced on the fetal than on the maternal side.     

Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction

Using a mid- to late-gestation ovine model of intrauterine growth restriction (IUGR), we examined uteroplacental blood flow and fetal growth during melatonin supplementation as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% [adequate; (ADQ)] or 60% [restricted (RES)] of nutrient requirements until day 130 of gestation. Umbilical artery blood flow was increased from day 60 to day 110 of gestation in MEL vs. CON dams, while umbilical artery blood flow was decreased from day 80 to day 110 of gestation in RES vs. ADQ dams. At day 130 of gestation, uteroplacental hemodynamics, measured under general anesthesia, and fetal growth were evaluated. Uterine artery blood flow was decreased in RES vs. ADQ dams, while melatonin supplementation did not affect uterine artery blood flow. Total placentome weight and placentome number were not different between treatment groups. Fetal weight was decreased by nutrient restriction. Abdominal girth and ponderal index were increased in fetuses from MEL-ADQ dams vs. all other groups. Fetal biparietal distance was decreased in CON-RES vs. CON-ADQ dams, while melatonin supplementation rescued fetal biparietal distance. Fetal kidney length and width were increased by maternal melatonin treatment. Fetal cardiomyocyte area was altered by both maternal melatonin treatment and nutritional plane. In summary, melatonin may negate the consequences of IUGR during specific abnormalities in umbilical blood flow as long as sufficient uterine blood perfusion is maintained during pregnancy.     

Randomised controlled trial of atenolol and pindolol in human pregnancy: effects on fetal haemodynamics.

OBJECTIVE--To compare the effects of uteroplacental circulation of two beta adrenoceptor blockers, atenolol (cardioselective) and pindolol (non-selective with intrinsic sympathomimetic activity). DESIGN--Controlled double blind double dummy study. SETTING--Departments of obstetrics and gynaecology in two Swedish university hospitals. SUBJECTS--29 women with pregnancy induced hypertension in the third trimester, 13 randomised to atenolol and 16 to pindolol. MAIN OUTCOME MEASURES--Pulsatility index in fetal aorta, umbilical artery, and maternal arcuate artery. Volumetric blood flow in fetal aorta and umbilical vein. RESULTS--Mean arterial blood pressure decreased by 9.0 (95% confidence interval -13.0 to -5.0) mm Hg in the atenolol group and by 7.8 (-11.4 to -4.2) mm Hg in the pindolol group. During atenolol treatment the pulsatility index increased significantly from 1.82 (SD 0.20) to 2.07 (0.32) in the fetal thoracic descending aorta, from 1.44 (0.28) to 1.79 (0.27) in the abdominal aorta, and from 0.93 (0.17) to 1.05 (0.19) in the umbilical artery; the volumetric blood flow in the umbilical vein decreased from 106 (28.8) to 84 (22.6) ml/min/kg. No such changes were seen after treatment with pindolol. Birth weight was similar in the two groups but placental weight was significantly different (529 (122) g in atenolol group v 653 (136) g in pindolol group; p = 0.03). CONCLUSION--The hypotensive effect was similar with both drugs, but only the beta 1 blocker atenolol had significant effects on fetal haemodynamics, although within normal ranges. The implications of these findings can be only speculative, but negative fetal consequences of beta 1 adrenoceptor blockade cannot be excluded.     

The response of the umbilical and femoral artery pulsatility indices in fetal sheep to progressively reduced uteroplacental blood flow

Fetal artery Doppler velocimetry may provide noninvasive information on the state of fetal oxygenation. It was hypothesized that during decreasing fetal oxygenation, the pulsatility index in the femoral artery will increase, whereas the pulsatility index in the umbilical artery will not change. Decreasing fetal oxygenation was induced in ten chronically-instrumented fetal sheep by progressive occlusion of the maternal common internal iliac artery. The pulsatility index in the umbilical artery was serially measured in six fetuses (group I, n = 6) and the pulsatility index in the femoral artery was serially measured in four fetuses (group II, n = 4). Fetal arterial oxygen content decreased by 72% in group I (P less than 0.0001) and by 79% in group II (P less than 0.0001). Fetal heart rate did not change. Fetal blood pressure increased by 11% in group I (P less than 0.02) and by 15% in group II (P less than 0.005). The umbilical artery pulsatility index (group I) did not significantly change during decreasing fetal oxygenation, whereas the femoral artery pulsatility index (group II) increased by 150% (P less than 0.005). It is concluded that progressively reduced uteroplacental blood flow results in fetal hypoxaemia, which is associated with increased pulsatility index in the femoral artery, while the pulsatility index in the umbilical artery does not change.     

Insulin induced fetal hypoglycaemia and fetal and maternal plasma prostaglandin concentrations in sheep in late gestation.

Fetal hypoglycaemia consequent on food withdrawal for 48 h in sheep in late pregnancy is accompanied by an increase in fetal PGE2 plasma concentrations and myometrial contractility. To assess the contribution of fetal hypoglycaemia and related cellular glucopenia in the increased production of fetal PGE2 we studied the effect of 48 h insulin infusion to the fetus. Fetal whole blood glucose was lowered from 19 +/- 2 to 9 +/- 1 mg.dl-1. This experimental regimen maintains glucose availability to those fetal cells in which insulin increases glucose uptake. Fetal umbilical venous and femoral arterial PGE2 concentrations and umbilical veno-arterial PGE2 difference were unchanged, but maternal uterine veno-arterial difference for PGFM increased during the insulin induced fetal hypoglycaemia. Myometrial activity was also unchanged. We conclude that the increased fetal PGE concentration previously reported during food withdrawal is due to a deficiency of glucose to specific insulin dependent cells within vascular beds served by the fetal cardiovascular system. In addition, the findings suggest a need for a supply of glucose of fetal origin for cells that are responsible for increased PGFM concentrations in the maternal uteroplacental circulation.     

Transplacental carbohydrate and sugar alcohol concentrations and their uptakes in ovine pregnancy

The concentrations of glucose, fructose, sorbitol, glycerol, and myo-inositol in sheep blood and tissues have been reported previously (1--5). However, the other polyols that are at low concentrations have not been investigated in pregnant sheep due to technical difficulties. By using HPLC and gas chromatography-mass spectrometry, seven polyols (myo-inositol, glycerol, erythritol, arabitol, sorbitol, ribitol, and mannitol) and three hexoses (mannose, glucose, and fructose) were identified and quantified in four blood vessels supplying and draining the placenta (maternal artery, uterine vein, fetal artery, and umbilical vein). Uterine and umbilical blood flows were measured, and uptakes of all the polyols and hexoses in both maternal and fetal circulations were calculated. There was a significant net placental release of sorbitol to both maternal and fetal circulations. Fructose was also taken up significantly by the uterine circulation. Maternal plasma mannose concentrations were higher than fetal concentrations, and there was a net umbilical uptake of mannose, characteristics that are similar to those of glucose. Myo-inositol and erythritol had relatively high concentrations in fetal plasma (697.8 plus minus 53 microM and 463.8 plus minus 27 microM, respectively). The ratios of fetal/maternal plasma arterial concentrations were very high for most polyols. The concentrations of myo-inositol, glycerol, and sorbitol were also high in sheep placental tissue (2489 plus minus 125 microM/kg wet tissue, 2119 plus minus 193 microM/kg wet tissue, and 3910 plus minus 369 microM/kg wet tissue), an indication that these polyols could be made within the placenta.     

Serum prolactin level changes in the maternal and fetal circulation between the 28th-40th weeks of pregnancy

Serum prolactin concentration was determined in blood samples taken from the maternal cubital vein, the umbilical vein and artery between the 28th-40th weeks of pregnancy from 108 parturients, of whom 74 gave birth prematurely and 34 gave birth at term. Results indicated that during this period the prolactin level rose in the umbilical vein and artery but not in the maternal vein. Correlative analysis showed a significant positive correlation between gestational age and the serum prolactin concentration of umbilical arterial and venous blood, but no correlation was found in the case of maternal blood. During the 28th-32nd weeks the prolactin level of maternal blood was found to be higher than that of umbilical blood while during the 33rd-36th weeks and at the 40th week the prolactin level was higher in the umbilical vein and artery. No correlation was found between the prolactin concentration of maternal and umbilical blood. On the basis of these results the authors conclude that fetal prolactin concentration changes occur independently of the maternal organism and increases during the 28th-40th weeks of pregnancy.     

Placental transport of free palmitic and linoleic acids in the guinea pig

Radioisotopic tracers were used to measure the unidirectional transfer rates of free fatty acids across the placenta of fed and fasted pregnant guinea pigs. Free (14)C-labeled palmitic and linoleic acids (in serum) were injected simultaneously into a jugular vein of an anesthetized pregnant guinea pig. Serial samples of maternal blood were collected from a carotid artery; fetal blood was collected from the umbilical vein of an exposed fetus. Analysis of maternal and fetal plasma revealed that: (a) the half-lives of free palmitic and linoleic acid in maternal plasma are approximately 1.3 min and 0.7 min, both in fed animals with low plasma concentrations of these acids and in fasted animals with high concentrations; (b) free linoleic and palmitic acids cross the placenta from maternal to fetal plasma in a ratio of approximately 2.0, a value which appears not to change as the transfer rates of these acids from maternal to fetal plasma are increased by fasting the mother. It is suggested that the ratio in which free linoleic and palmitic acids cross the placenta from maternal to fetal plasma is determined by the ratio of the unbound free linoleic and palmitic acid concentrations in maternal plasma. A comparison of several species indicates that a much greater proportion of fetal fatty acids comes from the mother in the guinea pig and rabbit than in the rat, the sheep, or man.     

Secretion of unconjugated estrone during pregnancy and around parturition in goats

The secretion of unconjugated estrone and its production site in pregnant goats were investigated in vivo. The mean estrone concentration (n = 15) in the peripheral plasma increased gradually, being 83 pg/ml on Day 40 and 483 pg/ml on Day 140 after mating. The estrone concentration increased rapidly after Day 2 before partum, reaching a peak at parturition (2370 pg/ml), and falling to 171 pg/ml at Day 1 post partum. The concentrations of estrone from the umbilical vein and umbilical artery did not differ from that found in the maternal jugular vein, suggesting that the fetus does not take part in estrogen production. The estrone concentration from the uterine vein after the fetus was removed was higher than the concentrations found in the maternal jugular vein and umbilical artery. In the placental tissue, a high concentration of estrone (18157 pg per gram of wet tissue) was detected. These findings suggest that the main production site of unconjugated estrone is the placenta.     

Suppression of trophoblast uterine spiral artery remodeling by estrogen during baboon pregnancy: impact on uterine and fetal blood flow dynamics

The present study was conducted to determine the impact of suppressing trophoblast remodeling of the uterine spiral arteries by prematurely elevating estrogen levels in the first trimester of baboon pregnancy on uterine and umbilical blood flow dynamics. Uteroplacental blood flow was assessed by Doppler ultrasonography after acute administration of saline (basal state) and serotonin on days 60, 100, and 160 of gestation (term: 184 days) to baboons in which uterine spiral artery remodeling had been suppressed by the administration of estradiol on days 25-59 of gestation. Maternal blood pressure in the basal state was increased (P < 0.01), and uterine artery diastolic notching and the umbilical artery pulsatility index and systolic-to-diastolic ratio, reflecting downstream flow impedance, were increased (P < 0.01) after serotonin administration on day 160, but not earlier, in baboons treated with estradiol in early gestation. These changes in uteroplacental flow dynamics in serotonin-infused, estradiol-treated animals were accompanied by a decrease (P < 0.05) in uterine and umbilical artery volume flow and fetal bradycardia. The results of this study show that suppression of uterine artery remodeling by advancing the rise in estrogen from the second trimester to the first trimester disrupted uteroplacental blood flow dynamics and fetal homeostasis after vasochallenge late in primate pregnancy.     

Concentrations of progesterone in arterial and venous plasma of fetal pigs and their dams in late gestation

Blood samples were drawn from uterine arteries and veins of pregnant gilts and from the umbilical artery and vein of each of their fetuses during laparotomy at Day 80. Concentrations of progesterone (P) were greater in fetal than maternal plasma. Uptake of P from the placenta by the fetal blood was evident but was not equivalent to the maternal uterine arterial-venous difference in P concentration. No correlation between plasma P and fetal weight was noted. Concentrations of P in both umbilical vessels of female fetuses were higher than in male fetuses. These data indicate that fetal sex affects the rate of transport and/or synthesis of P in the utero/placental compartment and/or the rate of metabolism of P in the fetus. The relative importance of de novo synthesis and transplacental transport of P in establishing concentrations of P in fetal blood remains to be elucidated.     

A dystocia and caesarean section model to characterize uteroplacental prostaglandin concentrations associated with retained placenta in dairy cattle

Plasma concentrations of prostaglandin F(2a) (PGF(2a), 13, 14-dihydro-15-keto-prostaglandin F(2a) (PGFM), prostaglandin E(2) (PGE(2)) and 13,14-dihydro-15-keto-prostaglandin E(2) (PGEM) were determined by RIA in blood samples taken from the jugular vein and the uteroplacental circulation (umbilical vein, umbilical artery and uterine vein) of 13 Holstein Friesian cows during caesarean section. According to discharge of placenta cows were divided in 2 groups. Group I (shedding of placenta within 12 hours, NRP, n=8) and Group II (retained placenta, RP, n=5). In blood samples taken from the jugular vein before surgery, no significant differences existed between groups regarding PGF(2a), PGFM, PGE(2) and PGEM. Concentrations of PGF(2a) and PGFM in the uteroplacental circulation of NRP cows were significantly higher than those of RP cows (except for PGFM in the umbilical vein). For all sampling sites except the jugular vein before surgery, PGE(2) and PGEM levels of NRP cows were significantly higher compared to RP cows.     

A Study to Determine if Acute Maternal and Fetal Hyperglycemia/Insulinemia Induces Leptin Production during Pregnancy.

BACKGROUND: In pregnant primates, the effect of post-prandial hyperglycemic or insulinemic states on leptin production is not known. Our goal was to conduct a controlled study using an established pregnant baboon model ( PAPIO ANUBIS) to determine whether acute glucose changes would have an effect on maternal or fetal plasma leptin levels. METHODS: Two animals were operated on at 138 and 140 days of gestation (term approximately 184 days) by placing 4 cannulae in the maternal aorta, inferior vena cava, fetal carotid artery, and the amniotic cavity. At 145 and 150 days, glucose infusions were started via the maternal femoral vein. Animal 1 received 7.5 gm of glucose over a 2-hour period at 145th day. Animal 2 received 20 gm of glucose over a 1-hour period at 150th day. Both animals remained AD LIBITUM throughout the experiments. Maternal and fetal blood samples were obtained from the arterial lines before the glucose infusion and at half hour intervals to include 30 minutes post-infusion. RESULTS: Significant changes from baseline concentrations were observed for maternal and fetal glucose and insulin concentrations in response to both glucose challenges. Maternal and fetal plasma leptin concentrations did not correlate with glucose or insulin changes. CONCLUSION: This preliminary study demonstrated that in primates, acute changes in circulating maternal or fetal glucose or insulin concentration do not affect maternal or fetal plasma leptin concentrations. These results suggest that alterations in leptin secretion by the maternal-placental-fetal unit may only occur in pathological states.     

Doppler evaluation of maternal and foetal vessels during normal gestation in queen

The aim of this work is to evaluate the haemodynamic characteristics of maternal and foetal vessels during normal pregnancy in queens, using colour Doppler and pulsed wave Doppler ultrasonography, in order to obtain information about maternal and foetal circulation. The blood waveforms of the uteroplacental arteries, aorta, caudal cava vein and umbilical cord of the fetuses were recorded weekly in seven healthy pregnant queens. Also, the measurements of peak systolic, end diastolic velocities, resistance and pulsatility indices were carried out. Uteroplacental blood flow was biphasic while the ones of the umbilical artery and aorta were first systolic and then diastolic. The caudal cava vein showed a typical waveform of venous vessels. During gestation the EDV and PSV of foetal vessels increased ( < 0.05) while the PI and RI of all vessels examined decreased ( < 0.05) except for the IP of the aorta. The Doppler ultrasonography, also in queens, can be used to evaluate the characteristics of maternal and foetal vessel flow and their progressive changes during pregnancy. This study can be considered the basis for further contribution in diagnosing and monitoring high-risk pregnancies in Veterinary Medicine.     

Anandamide levels in human female reproductive tissues: Solid-phase extraction and measurement by ultraperformance liquid chromatography tandem mass spectrometry

Anandamide (N-arachidonoylethanolamide), a bioactive lipid, is reported to play a role in pregnancy maintenance and parturition. Our aims were to (1) evaluate AEA levels at the human maternal:fetal interface and (2) validate the use of solid-phase extraction of AEA from tissues. AEA was analyzed in cord and maternal blood, amniotic fluid, placenta, and fetal membranes collected during Caesarean section (n = 14). Extraction efficiencies were 42 and 36% for the placenta and the fetal membranes, respectively. Tissue AEA was quantified using an isotope-dilution method and UPLC-ESI-MS/MS giving intra- and inter-day variability for tissues spiked with 0.2, 1, and 5 pmol/g AEA of less than 12%. Accuracy for these spiked samples was between 95% and 103% for fetal membranes and between 99% and 114% for placenta. Mean AEA concentrations were 2.72 ± 1.04 pmol/g for placenta and 1.19 ± 0.68 pmol/g for fetal membranes, and 0.93 ± 0.28, 0.88 ± 0.33, 0.77 ± 0.30, and 0.06 ± 0.04 nM for maternal, umbilical vein, and umbilical artery plasma and amniotic fluid. Higher AEA concentrations were found in placenta compared to fetal membranes (P < 0.0001), in umbilical vein compared with umbilical artery (P = 0.0015), and in plasma from maternal circulation compared with umbilical artery (P = 0.0152). The relevance of these changes in AEA concentrations at the maternal:fetal interface requires further investigation.