Uterine Venous Research Articles

The role of 1-Deoxysphingolipids and Polyamines in the pathogenesis of placental syndrome

BackgroundPlacental syndrome, mainly composed of preeclampsia and fetal growth restriction, has an impact on the health of mother and baby dyads. While impaired placentation is central to their pathophysiology, the underlying molecular mechanisms remain incompletely understood. This study investigates the association between placental syndrome and metabolic alterations in 1-deoxysphingolipids (1-deoxySLs) and polyamines, along with their regulatory enzymes.MethodsThis prospective case-control study involved 26 healthy pregnant women and 17 with placental syndrome. Blood samples were collected from maternal, uterine venous, and umbilical cord veins. Levels of 1-deoxySL, spermine, and spermidine, as well as related enzymes of polyamine metabolism such as ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SSAT), polyamine oxidase (PAO), and spermine oxidase (SMO), were measured using the techniques of LC-MS and ELISA, respectively.ResultsWomen with placental syndrome had significantly higher levels of 1-deoxySL, spermine, and spermidine in all blood samples compared to the healthy pregnancy group. Additionally, ODC and SSAT levels were reduced significantly in the placental syndrome group, while PAO and SMO levels showed no significant differences. Strong positive correlations were found between the studied enzymes and biomolecules in healthy pregnancies, which were notably weaker in the placental syndrome group.ConclusionThis study demonstrates significantly altered levels of 1-deoxySL and polyamines, with corresponding enzyme activity changes, in placental syndrome compared to healthy pregnancies. The disrupted correlations between these biomolecules suggest alterations in their metabolic pathways and potential utility as biomarkers. Further mechanistic studies are warranted to elucidate their role in placental syndrome pathophysiology.

The effect of pelvic pathology on uterine vein diameters

BackgroundTransvaginal ultrasound (TVS) is a sensitive tool for detecting various conditions that contribute to pelvic pain. TVS can be also used to assess blood flow and measure the size of pelvic veins. Pelvic venous congestion (PVC) is characterised by enlargement of the pelvic veins and has been recognised as a cause of chronic pelvic pain. The reference ranges for uterine venous diameter in women with normal pelvic organs have been established, but there is no information regarding the potential effect of pelvic pathology on the uterine venous diameters. The aim of this study was to examine the size of uterine venous plexus in women with evidence of pelvic abnormalities on TVS and to determine whether the reference ranges need to be adjusted in the presence of pelvic pathology.A prospective, observational study was conducted in our gynaecological outpatient clinic. Morphological characteristics of all pelvic abnormalities detected on TVS and their sizes were recorded. The uterine veins were identified and their diameters were measured in all cases. The primary outcome measure was the uterine venous diameter. Regression analyses were performed to determine factors affecting the uterine venous size in women with pelvic pathology.ResultsA total of 1500 women were included into the study, 1014 (67%) of whom were diagnosed with pelvic abnormalities. Women with pelvic pathology had significantly larger uterine venous diameters than women with normal pelvic organs (p < 0.01). Multivariable analysis showed that pre-menopausal status, high parity, presence of fibroids (p < 0.001) and Black ethnicity were all associated with significantly larger uterine vein diameters. Based on these findings modified reference ranges for uterine venous diameters have been designed which could be used for the diagnosis of PVC in women with uterine fibroids.ConclusionsOur findings show that of all pelvic pathology detected on TVS, only fibroids are significantly associated with uterine venous enlargement. Factors known to be associated with enlarged veins in women with normal pelvic organs, namely parity and menopausal status, also apply in patients with pelvic pathology. Future studies of uterine venous circulation should take into account the presence and size of uterine fibroids when assessing women for the signs of PVC.

Pregnancy recognition signaling mechanisms in ruminants and pigs

Maternal recognition of pregnancy refers to the requirement for the conceptus (embryo and its associated extra-embryonic membranes) to produce a hormone that acts on the uterus and/or corpus luteum (CL) to ensure maintenance of a functional CL for production of progesterone; the hormone required for pregnancy in most mammals. The pregnancy recognition signal in primates is chorionic gonadotrophin which acts directly on the CL via luteinizing hormone receptors to ensure maintenance of functional CL during pregnancy. In ruminants, interferon tau (IFNT) is the pregnancy recognition signal. IFNT is secreted during the peri-implantation period of pregnancy and acts on uterine epithelia to silence expression of estrogen receptor alpha and oxytocin receptor which abrogates the oxytocin-dependent release of luteolytic pulses of prostaglandin F2-alpha (PGF) by uterine epithelia; therefore, the CL continues to produce progesterone required for pregnancy. Pig conceptuses secrete interferon delta and interferon gamma during the peri-implantation period of pregnancy, but there is no evidence that they are involved in pregnancy recognition signaling. Rather, pig conceptuses secrete abundant amounts of estrogens between Days 11 to 15 of pregnancy required for maternal recognition of pregnancy. Estrogen, likely in concert with prolactin, prevents secretion of PGF into the uterine venous drainage (endocrine secretion), but maintains secretion of PGF into the uterine lumen (exocrine secretion) where it is metabolized to a form that is not luteolytic. Since PGF is sequestered within the uterine lumen and unavailable to induce luteolysis, functional CL are maintained for production of progesterone. In addition to effects of chorionic gonadotrophin, IFNT and estrogens to signal pregnancy recognition, these hormones act on uterine epithelia to enhance expression of genes critical for growth and development of the conceptus.

Life or Death Decisions in the Corpus Luteum

The corpus luteum (CL) is an ephemeral endocrine organ. During its lifespan, it undergoes a period of extremely rapid growth that involves hypertrophy, proliferation and differentiation of the steroidogenic cells, as well as extensive angiogenesis. The growth phase is followed by a period in which remodelling of the tissue ceases, but it engages in unparalleled production of steroids, resulting in extraordinarily high metabolic activity within the tissue. It is during this stage that a critical juncture occurs. In the non-fertile cycle, uterine release of prostaglandin (PG)F(2α) initiates a cascade of events that result in rapid loss of steroidogenesis and destruction of the luteal tissue. Alternatively, if a viable embryo is present, signals are produced that result in rescue of the CL. This review article summarizes the major concepts related to the fate of the CL, with particular focus on recent insights into the mechanisms associated with the ability of PGF(2α) to bring about complete luteolysis. It has become clear that the achievement of luteolysis depends on repeated exposure to PGF(2α) and involves coordinated actions of heterogeneous cell types within the CL. Together, these components of the process bring about not only the loss in progesterone production, but also the rapid demise of the structure itself.

Placental ischemia and changes in umbilical and uteroplacental arterial and venous hemodynamics

Objective: To relate Doppler velocimetry findings in fetoplacental and uteroplacental circulation to placental histomorphology. Material and methods: In 14 uncomplicated and 31 high-risk pregnancies Doppler velocimetry was performed in umbilical artery and vein, and in maternal uterine veins and arteries during the second half of gestation. Histopathology of the placentas was examined, especially for signs of ischemia and inflammation. Results: All fetuses in uncomplicated pregnancies had normal flow velocity waveforms in umbilical artery; in the high-risk group, 18 fetuses had abnormal flow (increased PI or absent/reverse end-diastolic flow). The latter group had more often high ischemic score and infarctions in the placenta than found in pregnancies with normal umbilical artery flow (p < 0.001 and p = 0.02, respectively). Similarly, the abnormal uterine artery flow pattern (uterine artery score 3–4) occurred more often with high ischemic score and placenta infarctions (p < 0.001 and p < 0.001, respectively). No significant associations were found between the uterine venous flow type and placental ischemia. Conclusion: Placental ischemic morphological changes were associated with Doppler ultrasound signs of increased resistance to arterial blood flow, both on the fetal and maternal sides of the placenta. No significant relation to the uterine venous flow velocities was found.

Sildenafil Citrate Treatment Enhances Amino Acid Availability in the Conceptus and Fetal Growth in an Ovine Model of Intrauterine Growth Restriction1–3

Adequate placental blood flow is essential for the optimal delivery of nutrients from mother to fetus for conceptus growth. Restricted fetal development results from pathophysiological and environmental factors that alter utero-placental blood flow, placental function, and, therefore, nutrient availability in the fetus. To test this hypothesis, 0, 75, or 150 mg/d sildenafil citrate (Viagra) was administered subcutaneously from d 28 to 115 of gestation to either nutrient-restricted [50% of NRC requirements) or adequately-fed ewes (100% of NRC requirements). On d 115, maternal, fetal, and placental tissues and fluids were collected. Concentrations of total amino acids and polyamines in uterine venous and arterial sera, amniotic and allantoic fluids, and fetal umbilical venous serum were lower (P < 0.05) in nutrient-restricted ewes than in adequately fed ewes, as were the ratios of total amino acids in fetal umbilical venous serum to uterine arterial serum. Sildenafil citrate dose-dependently increased (P < 0.05) total amino acids and polyamines in amniotic fluid, allantoic fluid, and fetal serum without affecting values in maternal serum. Fetal weight was lower (P < 0.05) in nutrient-restricted ewes on d 115. Sildenafil citrate treatment dose-dependently increased (P < 0.05) fetal weight in both nutrient-restricted and adequately fed ewes. This study supports the hypothesis that long-term sildenafil citrate treatment enhances fetal growth, at least in part, by increasing the availability of amino acids in the conceptus. These findings may lead to the clinical use of sildenafil citrate in human pregnancies suspected to be at risk for intrauterine fetal growth retardation.

An Obstetric Point of View on Fetal Adaptation and Reprogramming

After completing this article, readers should be able to: 1. Define the difference between fetal adaptation and fetal programming. 2. Describe the mechanisms involved in maintaining fetal oxygenation. 3. Describe how maternal glycemic control affects fetal growth and development. 4. List the known stimuli involved in fetal programming in humans. For pregnant women who want to have healthy babies and their obstetricians, the period extending from several weeks prior to conception until birth is of obvious interest. Problems affecting pregnancy may have consequences on the developing fetus resulting from adaptation or reprogramming. An adaptation is the action or process of adapting or being adapted. Adaptation implies a change by which an organism becomes better suited to its environment. Programming describes the mechanisms by which a stimulus or insult at a critical period of development has lasting or lifelong effects. Pregnancy affects all the determinants of oxygen delivery to the uteroplacental circulation. Maternal ventilation increases, which normally does not change arterial O2 saturation, although mild respiratory alkalosis ensues. Maternal hemoglobin concentrations decline due to greater expansion of plasma than red cell mass and reduced arterial O2 content. A rise in uteroplacental blood flow is due to higher cardiac output and redistribution of blood flow to favor uteroplacental circulation. Maternal cardiac output increases as a result of a decrease in systemic vascular resistance that begins in the luteal phase immediately following conception and an increase in blood volume. The fetus lives and grows in a relatively “hypoxic” environment compared with the adult. The fetal arterial Po2 is approximately 20 mm Hg compared with approximately 80 mm Hg in adults. The low fetal arterial Po2 can be attributed largely to the venous equilibration of placental gas exchange in which both maternal uterine venous and fetal umbilical venous vasculature streams run in …

P10.09: Uterine venous flow in normal and complicated pregnancies—a methodological study

P10.09: Uterine venous flow in normal and complicated pregnancies—a methodological study

212. Follistatin secretion by the ovary is not directly related to PGF2α induced luteolysis in the ewe

Follistatin is a monomeric glycoprotein, expressed ubiquitously, and found in greatest levels in ovarian tissue. Our previous studies have demonstrated that ovarian venous follistatin levels are elevated at the same time as spontaneous luteolysis in merino ewes, but remain constant in circulating and uterine plasma across oestrous. It was hypothesized that the follistatin elevation may be part of functional luteolysis in the ovary. A cross-sectional study of ovarian venous follistatin during luteolysis was performed using merino ewes, which were synchronized with intravaginal sponges. Luteolysis was induced 10 days after oestrus using a PGF2α (IM) injection. Circulating (jugular and arterial), uterine venous and ovarian venous (luteinized and contralateral) blood samples were taken under general anaesthesia at times 0, 6, 12, 24, 36, 48 and &gt;48 h (54–71 h) after the PGF2α injection. All samples were assayed for progesterone by RIA and follistatin using a specific follistatin antiserum (#204) in a competitive ELISA with rhFS-288 used as standard. Progesterone concentrations in the venous plasma from the luteinized ovaries plasma were significantly higher than those in the contralateral ovarian and circulating plasma. As expected progesterone concentrations began declining within 6 h and continued until 24 h after PGF2α. Mean circulating plasma follistatin concentrations were similar throughout the experiment with overall means of 9.9 ± 0.5 ng/mL. Both luteinized and contralateral ovarian venous plasma follistatin concentrations (11.8 ± 3.4 ng/mL) were not significantly different from circulating concentrations. However at 48 h ovarian venous follistatin concentrations were significantly elevated (22.5 ± 2.3 ng/mL) and remained elevated for at least 71 h (29.5 ± 7.9 ng/mL). This experiment confirms our previous work that both luteinized and contralateral ovarian venous follistatin concentrations do elevate concurrently with each other but that the elevation in follistatin is not directly related to functional luteolysis as induced by PGF2α.

Umbilical Threonine Uptake during Maternal Threonine Infusion in Sheep

Objective: The infusion into the maternal circulation of amino acid solutions failed to increase umbilical threonine (THR) uptake above normal even when THR was present in the infusate at a relatively high concentration. The purpose of the present study was to determine whether umbilical THR uptake can be increased by infusing a THR solution that does not contain any other amino acids.Study design: Five pregnant sheep (130±1.0 days after conception) were infused for 2h with a threonine solution (4.4±0.2μmol·kg−1·min−1). Plasma amino acids, glucose and lactate, hematocrit, blood O2 content in maternal arterial, uterine venous, umbilical arterial and venous blood were measured. Uterine and umbilical blood flows were measured before and during the infusion and were used to calculate uterine and umbilical uptakes. Maternal and foetal plasma insulin and glucagon concentrations were also measured.Results: The THR infusion increased maternal plasma THR (904 vs 236μm , P< 0.001), foetal plasma THR (539 vs 334μm , P< 0.01), and both uterine (20.4 vs 4.7μmol·min−1·kg−1fetalweight, P< 0.05) and umbilical (8.6 vs 3.8μmol·min−1·kg−1fetalweight, P< 0.001) THR uptakes. The uterine-umbilical THR uptake difference increased significantly (11.8 vs 0.9μmol·min−1·kg−1fetalweight, P< 0.05). There were significant (P< 0.001) decreases in the foetal arterial plasma concentrations of tyrosine and the branched chain amino acids, as well as in isoleucine umbilical uptake (P< 0.05). There was a significant increase in maternal plasma glucagon (P< 0.01).Conclusion: A maternal THR infusion that causes a 3.8-fold increase in maternal plasma THR concentration above normal, with no significant increase in the concentration of other amino acids, leads to a 2.3-fold increase in umbilical THR uptake. This contrasts with the absence of a significant increase in umbilical THR uptake when THR was infused as part of an amino acid mixture in previous studies. The evidence supports the hypothesis that, in vivo, THR flux from placenta to foetus is mediated by a saturable, rate limiting transport system which is subject to inhibition by other neutral amino acids.

Old, new and the newest concepts of inhibition of luteolysis during early pregnancy in pig

In 1977 Bazer and Thatcher proposed that maternal recognition of pregnancy in the pig involves the secretion of PGF 2α towards the uterine lumen (exocrine) rather than towards the uterine venous drainage (endocrine) as occurs in the non-pregnant pig during the mid to late stages of the estrous cycle. The retrograde transfer of PGF 2α from the venous blood and uterine lymph into the uterus and the ability of the uterine vein and artery wall to accumulate PGF 2α could constitute a part of putative mechanism of corpus luteum protection during early pregnancy. A luteotropic/anti-luteolytic effect of PGE 2 in the pig also has been frequently demonstrated and it seems that the most effective agent in changing PGE 2:PGF 2α secretion is estradiol. The role for oxytocin during luteolysis and early pregnancy is controversial. It appears, however, that the main function of this hormone is autocrine and/or paracrine stimulation of PGF 2α secretion. Pig trophoblastic interferons, unlike those of ruminants, do not themselves exert an anti-luteolytic effect in pigs. It is likely, that cytokines and angiogenic growth factors are involved in the initiation of luteolysis and/or maintenance of corpora lutea (CL). A discovery of functional LH receptors in porcine endometrium opened a new possibility for this hormone in luteolysis and perhaps in recognition of pregnancy in pigs. The endogenous LH pulses can provoke prostaglandin secretion from endometrium in pigs. On the other hand prolongation of up-regulation of LH receptors in endometrium of early pregnant gilts can additionally increase angiogenic factor production before the process of implantation is completed. Finally new integrated concepts of luteolysis and inhibition of luteolysis in pigs based on selectively reviewed information are presented.

Metabolic alterations in the fetal hepatic and umbilical circulations during glucocorticoid-induced parturition in sheep.

Fetal hepatic amino acid metabolism has unique features in comparison to postnatal life. Thus, it seemed likely that this metabolism might be changed by the endocrine changes which precede birth. To explore the changes in placental and fetal carbohydrate and amino acid metabolism that occur during parturition, labor was induced in six ewes at 131 +/- 1 d gestation with a fetal infusion of dexamethasone. For purpose of chemical analysis, blood was withdrawn before and approximately 3 and 25 h from the start of the infusion from maternal arterial, uterine venous, umbilical venous, fetal arterial, and left hepatic venous catheters. Fetal oxygenation remained normal. At 25 h, both fetal and maternal arterial plasma glucose concentrations increased (p < 0.01 and p < 0.02, respectively) and umbilical glucose uptake decreased (p < 0.05). Fetal glutamate showed a significant reduction in its hepatic output (p < 0.05) with a concomitant reduction in fetal arterial plasma concentration (p < 0.05) and placental uptake (p < 0.01). Fetal plasma concentrations of several other amino acids were markedly increased. The reduction in placental glutamate uptake was temporally associated with a decline in progesterone release by the pregnant uterus. These data suggest the hypothesis that glutamate plays a role in integrating the complex changes in placental and fetal hepatic metabolism that occur during parturition.

An Unusual Case of Maternal-Fetal Death Due to Vaginal Insufflation of Cocaine

Air embolism secondary to vaginal insufflation has been documented as a cause of death in pregnant women. Under pressure, the air enters the uterus, causing air emboli within the uterine venous drainage and subsequently the systemic circulation. Death is usually sudden as the air obstructs the normal flow of circulation. Acute cocaine toxicity is also a well-known cause of sudden death. Cocaine use is prevalent in our society, even among pregnant women. We report the sudden death of a 31-year-old gravid female and 39-week gestational age male fetus. The cause of death was air embolism secondary to oral-vaginal insufflation of cocaine smoke.

Ritodrine increases leukotriene B 4 concentrations in pregnant sheep

Our goals were (1) to determine if beta-adrenergic receptor stimulation leads to 5-lipoxygenase metabolism of arachidonic acid and (2) to determine if inhibition of prostaglandin synthase alters 5-lipoxygenase metabolism of arachidonic acid during beta-adrenergic stimulation. We infused saline solution, ritodrine (4 micrograms/kg/min), and a combination of ritodrine (4 micrograms/kg/min) and ketorolac (1.2 microgram/kg/min) into chronically catheterized pregnant sheep (gestational ages 110 to 120 days, term 147 days). With a radioimmunoassay we measured concentrations of leukotriene B4, a 5-lipoxygenase metabolite of arachidonic acid, in uterine venous and arterial plasma at 0, 2, and 4 hours during the infusion. Both uterine venous and arterial leukotriene B4 were increased during ritodrine infusion (mean uterine venous increase at 2 hours 218%, p < 0.05; mean arterial increase at 2 hours 280%, p < 0.05). Concentrations during combined infusion of ritodrine and ketorolac increased significantly but were not different than concentrations observed during ritodrine infusion. Infusion of the beta-agonist ritodrine leads to 5-lipoxygenase metabolism of arachidonic acid and increased concentrations of leukotriene B4. The increased concentration in both uterine venous and arterial plasma suggests a systemic source of leukotriene B4 production. Concurrent inhibition of prostaglandin synthase during ritodrine infusion does not change 5-lipoxygenase metabolism in this model.

Increased uteroplacental production of prostaglandin E2 during ethanol infusion.

Experiments were conducted in 14 pregnant sheep to determine the effect of a 1-h maternal infusion of ethanol (1 g/kg maternal body wt) on placental efflux of prostaglandin E2 (PGE2), umbilical blood flow (Qum), and carbohydrate metabolism at 123-130 days gestation. This ethanol dosage regimen produced peak ethanol concentrations in fetal and maternal blood in the range of 1.48-1.64 mg/ml at the end of the infusion. Umbilical venous and fetal arterial PGE2 concentrations increased (P < 0.05) from 315 +/- 47 and 202 +/- 25 pg/ml to 740 +/- 172 and 489 +/- 67 pg/ml, respectively, at the end of the infusion. Placental secretion of PGE2 into the fetal circulation increased by 45% (P < 0.05). Uterine venous and maternal arterial PGE2 concentration increased (P < 0.05) from 370 +/- 27 and 262 +/- 28 pg/ml to 705 +/- 51 and 487 +/- 69 pg/ml, respectively. Fetal and maternal blood glucose concentration decreased (P < 0.05) from 0.98 +/- 0.11 and 2.88 +/- 0.25 mmol/l to 0.81 +/- 0.21 and 2.44 +/- 0.16 mmol/l, respectively. Fetal and maternal blood lactate concentration increased (P < 0.05) from 1.40 +/- 0.11 and 0.68 +/- 0.07 mmol/l to 1.67 +/- 0.14 and 1.82 +/- 0.16 mmol/l, respectively. Qum, fetal heart rate, fetal blood pressure, and fetal and maternal blood gases were unchanged by the ethanol infusion. These results support the hypothesis that the placenta is the major source of the elevated fetal and maternal plasma PGE2 concentrations produced in pregnant sheep by maternal ethanol administration.

Intrauterine pressure and fluid absorption during continuous flow hysteroscopy

Our objectives were to document the causes of fluid absorption during continuous flow hysteroscopy and to determine under which operative conditions fluid overload may occur. Fifteen patients underwent operative hysteroscopy with 2% ethanol solution for uterine distention. Absorption of fluid was measured by blood alcohol, sodium, osmolarity, and hematocrit. Intrauterine pressures were measured with an obstetric pressure catheter. Alcohol absorption was noted in one patient during a myoma resection. Two additional patients, not in the study, had fluid absorption after partial perforations of the uterus. Under normal operative conditions there were no changes in sodium, osmolarity, or hematocrit. Intrauterine pressures ranged from 45 to 75 mm Hg. Experimental pressures of greater than 200 mm Hg were not associated with fluid absorption. Intravasation of fluid may occur through open uterine venous channels with extensive resections and under low pressures in the presence of unrecognized perforations.

Effects of fetal anemia on PO2 difference between uterine venous and umbilical venous blood

In the fetus, the functional equivalent of the alveolar-arterial blood PO2 difference is the uterine venous-umbilical venous blood PO2 difference. Generally, factors that affect one of the venous blood PO2s produce equivalent effects on the other. We previously showed that fetal anemia produces increases in umbilical venous blood PO2. To determine whether this increase was associated either with equivalent increases in uterine venous blood PO2 or with reductions in the uterine venous-umbilical venous PO2 difference, we studied eight chronically catheterized pregnant sheep and fetal lambs. Measurements of O2 gas tensions and O2 saturations, uterine and umbilical blood flows, and uterine, fetal, and placental O2 consumptions were made in animals with normal fetal hematocrits and during reductions in fetal hematocrit of 35% (moderate fetal anemia) or 60% (severe fetal anemia). Fetal anemia produced reductions in the uterine venous-umbilical venous blood PO2 difference; in some cases the PO2 difference was less than 2 mmHg (compared with normal values of 20 mmHg). The development of both moderate and severe fetal anemia had no effect on uterine and umbilical blood flows or placental O2 consumption but did reduce total uterine and fetal O2 consumption. These data indicate that fetal anemia induces changes in placental gas transport. These changes may be due to improvements in gas diffusion, reductions in perfusion mismatching, or reductions in vascular shunting. Our data further indicate that placental O2 consumption rate, which is high in normal pregnant sheep, plays no role in the maintenance of the uterine venous-umbilical venous blood PO2 difference in pregnant sheep.

Uteroplacental production of eicosanoids in ovine pregnancy

Dramatic cardiovascular alterations occur during normal ovine pregnancy which may be associated with increased prostaglandin production, especially of uteroplacental origin. To study this, we examined (Exp 1) the relationships between cardiovascular alterations, e.g., the rise in uterine blood flow and fall in systematic vascular resistance, and arterial concentrations of prostaglandin metabolites (PGEM, PGFM and 6-keto-PGF 1α) in nonpregnant (n=4) and pregnant (n=8) ewes. To determine the potential utero-placental contribution of these eicosanoids in pregnancy, we also studied (Exp 2) the relationship between uterine blood flow and the uterine venous-arterial concentration differences of PGE 2, PGF 2α, PGFM, 6-keto-PGFP 1α, and YxB 2 in twelve additional late pregnant ewes. Pregnancy was associated with a 37-fold increase in uterine blood flow and a proportionate (27-fold) fall in uterine vascular resistance (p<0.01). Arterial concentrations of PGEM were similar in nonpregnant and pregnant ewes (316±19 and 245±37 pg/ml), while levels of PGFM and PGI 2 metabolites 6-keto-PGF 1α were elevated 23-fold (31±14 to 708±244 pg/ml) and 14-fold (12±4 to 163±78 pg/ml), respectively (p<0.01). Higher uterine venous versus uterine arterial concentrations were observed for PGE 2 (397±36 and 293±22 pg/ml) and 6-keto-PGF 1α (269±32 and 204±32 pg/ml), p<0.05, but not PGF 2α or TxB 2. Although PGFM concentrations appeared to be greater in uterine venous (1197±225 pg/ml) as compared to uterine arterial (738±150 pg/ml) plasma, this did not reach significance (0.05<p<0.1). In normal ovine pregnancy arterial levels of PGI 2 are increased, which may in part reflect increased uteroplacental production. Moreover the gravid ovine uterus also appears to produce PGE 2 and metabolize PGF 2α.

Mammary secretion of oestrogens and prostaglandin F 2α in cows near parturition

Oestrone and oestradiol-17β concentrations in mammary and uterine venous and aortal blood were determined by radioimmunoassay (RIA) in six Black-White cows from Day 7 prepartum to Day 1 postpartum. In four cows, the plasma levels of prostaglandin F 2α in the caudal superficial epigastric vein and the abdominal aorta were established by RIA around the same time. The mean oestradiol-17β concentration in mammary venous blood was higher than that in uterine and aortal blood. The mean levels of oestrone in aortal and mammary venous plasma were similar, but lower than those in the uterine vein. The mean concentration of PGF 2α was greater in mammary venous drainage than in aortal blood from Day 7 to Day 2 prepartum. The present experiment shows that oestrone is not secreted by the udder in cows and confirms the mammary secretion of oestradiol-17β and PGF 2α near parturition.

Placental oxygen transport in sheep with different hemoglobin types.

To study the effect of genetic differences in the maternal oxyhemoglobin dissociation curve on fetal O2 supply, we compared eight pregnant ewes homozygous for high O2 affinity hemoglobin (A) with eight pregnant ewes homozygous for low O2 affinity hemoglobin (B). Each ewe carried a single fetus. Fetal weights were not significantly different (A, 3,000 +/- 170 g; B, 3,070 +/- 270 g). The A ewes had significantly higher arterial O2 saturation (95 vs. 89.4%), uterine blood flow per kilogram of fetus (464 vs. 374 ml/min), uterine venous O2 saturation (78.1 vs. 67.5%), and placental-to-fetal weight ratio (0.107 vs. 0.085). Uterine venous PO2 was significantly less in A ewes (41.7 vs. 47.6 Torr), but umbilical venous and arterial PO2 and fetal O2 uptake were virtually equal in the two groups. We conclude that the difference in O2 affinity between A and B hemoglobins is fully compensated for by differences in arterial O2 saturation, in the rate of perfusion of the pregnant uterus, and in the degree of PO2 equilibration between the uterine and umbilical circulations so that the single fetuses of A and B hemoglobin carriers have equal levels of oxygenation.