Uterine blood flow, oxygen and glucose uptakes at mid-gestation in the sheep

In early ovine fetal development, the placenta grows more rapidly than the fetus so that at mid-gestation the aggregate weight of placental cotyledons exceeds fetal weight. The purpose of this study was to compare two separate methods of measuring uterine blood flow and glucose and oxygen uptakes in seven mid-gestation ewes, each carrying a single fetus. Uterine blood flow to both uterine horns was measured by microsphere and by tritiated water steady-state diffusion methodology. Calculations of tritiated water blood flows and oxygen and glucose uptakes were based on measurements of arteriovenous concentration differences across each uterine horn. The distribution of blood flow and oxygen uptake between the two uterine horns was strongly correlated with placental mass distribution. The two methods gave comparable results for uterine blood flow (457 +/- 35 vs 476 +/- 35 ml/min), oxygen uptake (457 +/- 35 vs 476 +/- 35 mumol/min), and glucose uptake (63 +/- 8 vs 64 +/- 6 mumol/min). Uterine blood flow was approximately 38% of the late gestation value and 56.1 +/- 1 times higher than umbilical blood flow. Uteroplacental oxygen consumption was about 58% of late gestation measurements and 3.9 +/- 0.5 times higher than fetal oxygen uptake. We confirm that the large placental mass of mid-gestation is associated with high levels of maternal placental blood flow and placental oxidative metabolism.     

Uterine blood flow of cows during the oestrous cycle and early pregnancy: effect of the conceptus on the uterine blood supply.

Blood flow to each uterine horn of cows during the oestrous cycle and early pregnancy was determined daily by use of electromagnetic blood flow probes placed around both middle uterine arteries. The pattern of blood flow to uteri of pregnant and non-pregnant cows was similar until Day 14 after mating or oestrus. Between Days 14 and 18 of pregnancy blood flow to the uterine horn containing the conceptus increased (P less than 0.01) 2- to 3-fold, whereas blood flow to the non-gravid uterine horn in these cows remained constant. No corresponding increase in blood flow to the uterine horn ipsilateral to the ovary bearing the CL was observed in non-pregnant cows during this 4-day period. By Day 19 of pregnancy, blood flow to the gravid uterine horn had returned to a level similar to that observed on Day 13. Blood flow to both uterine horns of pregnant cows remained constant from Days 19 to 25 and then increased to the gravid horn (P less than 0.01) markedly until Day 30 whereas blood flow to the non-gravid horn remained low. Uterine blood flow during the oestrous cycle of non-pregnant cows was positively correlated (P less than 0.01) with systemic concentrations of oestradiol and the ratio of oestradiol (pg/ml) to progesterone (ng/ml). There was no association between oestradiol concentrations and blood flow to the gravid uterine horn. These data indicate local control of uterine blood flow by the bovine conceptus which may function to create optimal conditions for the continuation of pregnancy.     

Exercise responses in pregnant sheep: oxygen consumption, uterine blood flow, and blood volume

In an attempt to explore the acute maternal responses to exercise we measured oxygen consumption, uterine blood flow, and blood volume in 13 chronically catheterized pregnant sheep at rest and while exercising on a treadmill. With maximal exercise O2 consumption increased 5.6 times, from a resting value of 5.8 +/- 0.3 (SE) to 32.1 +/- 2.8 ml X min -1 X kg -1, cardiac output increased 2.7 times, from 149 +/- 8 to 404 +/- 32 ml X min -1 X kg -1, and arteriovenous oxygen content difference increased 2.1 times, from 3.9 +/- 0.2 to 8.0 +/- 0.4 ml X dl -1. Total uterine blood flow decreased from a mean resting value of 292 +/- 6 to 222 +/- 19 ml X min -1 X kg fetus -1 near exhaustion during prolonged (40 min) exercise at 70% maximal oxygen consumption. Maternal blood volume decreased 14% (P less than 0.01) from 67.5 +/- 3.7 to 57.8 +/- 3.6 ml X kg -1 during this exercise period, with a 20% decrease in plasma volume without a change in red cell volume. We conclude that uterine blood flow decreases during maternal exercise. However, hemoconcentration helps to maintain a relatively constant oxygen delivery to the uterus.     

Responses of the uterine circulation to sympathetic nerve stimulation

Pregnant and non-pregnant sheep uteri were perfused in situ with arterial blood at a constant flow rate. Unilateral stimulation (1-2 ma, u ms pulse) of the distal end of the severed sympathetic chain (L3-L4) at frequencies between 5 and 25 Hz produced a graded increase in uterine artery pressure in both horns. At 25 Hz, pressure in the horn ipsilateral to the stimulated sympathetic chain increased by 28 +/ 2% in four pregnant animals and 32 +/ 5% in six non-pregnant ewes. The response of the contralateral horn was significantly smaller than that of the ipsilateral horn (P less than or equal to 0.05). The response was alpha-mediated since it was abolished by local injection of dibenzyline into the middle uterine artery. The responses of the pregnant and non-pregnant animals were similar, indicating that pregnancy did not alter the alpha-adrenergic responses of the uterine vasculature.     

Neuropeptide Y (NPY)-like immunoreactivity in guinea pig uterus is reduced during pregnancy in parallel with noradrenergic nerves

Summary Neuropeptide Y (NPY) is a recently discovered neuropeptide with vasoconstrictor effects when given in vivo. It occurs in many sympathetic neurons, where it appears to coexist with noradrenaline (NA). It is wellknown that profound changes in the levels of uterine NA occur in many species during pregnancy. Therefore we have investigated the distribution of catecholamine neurons and NPY by immunohistochemistry in the pregnant and nonpregnant guinea pig uterus. In the virgin uterus NPY-like immunoreactivity was present in nerve fibres and terminals in the smooth muscle layers of the uterine horns and around blood vessels. The distribution of NPY fibres was very similar to that of noradrenergic nerves visualized with antibodies against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). In the pregnant uterus, NPY- and TH-like immunoreactivity disappeared almost completely. In the cervix, a slight decrease of immunoreactivity was observed, whereas in the ovaries no changes were noted between the pregnant and nonpregnant condition. The results indicate that NPY and catecholamines coexists in the adrenergic neurons of the guinea pig uterus, cervix and ovary and that they vary together in the myometrium during pregnancy. We suggest that NPY may be of functional importance for the pregnant uterus.     

Neuropeptide Y (NPY)-like immunoreactivity in guinea pig uterus is reduced during pregnancy in parallel with noradrenergic nerves

Neuropeptide Y (NPY) is a recently discovered neuropeptide with vasoconstrictor effects when given in vivo. It occurs in many sympathetic neurons, where it appears to coexist with noradrenaline (NA). It is wellknown that profound changes in the levels of uterine NA occur in many species during pregnancy. Therefore we have investigated the distribution of catecholamine neurons and NPY by immunohistochemistry in the pregnant and nonpregnant guinea pig uterus. In the virgin uterus NPY-like immunoreactivity was present in nerve fibres and terminals in the smooth muscle layers of the uterine horns and around blood vessels. The distribution of NPY fibres was very similar to that of noradrenergic nerves visualized with antibodies against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH). In the pregnant uterus, NPY- and TH-like immunoreactivity disappeared almost completely. In the cervix, a slight decrease of immunoreactivity was observed, whereas in the ovaries no changes were noted between the pregnant and nonpregnant condition. The results indicate that NPY and catecholamines coexists in the adrenergic neurons of the guinea pig uterus, cervix and ovary and that they vary together in the myometrium during pregnancy. We suggest that NPY may be of functional importance for the pregnant uterus.     

Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection

Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and that the constitutively elevated uterine NO during pregnancy may help contain or even reduce the risk of infection-related complications.     

Triplex Doppler evaluation of uterine arteries in cyclic and pregnant domestic cats

The aims were to determine resistance index (RI) and pulsatility index (PI) in the uterine arteries of cyclic and pregnant domestic cats comparing the left and right uterine horns, as well as the majority or minority uterine horns, based on fetus number per horn; to determine the presence or absence of an early diastolic notch (EDN) in the uterine artery of pregnant queens. Ten domestic cats were followed during one cycle and one pregnancy until 63rd days after mating. The estrous cycle length was 16 ± 9.57 days. The uterine horn with the highest number of fetuses (majority uterine horn - MUH) presented 2.0 ± 1.0 fetus and the lower (minority uterine horn - miUH) presentes 0.78 ± 0.67 fetus. There were no differences in indexes between uterine arteries during the cycles and pregnancies. The RI and PI of MUH were lower than miUH (P<0.05). Uterine artery of the MUH presented lower indexes than miUH during the acceptance period (P<0.05). On D14 of pregnancy, uterine artery presented reductions in both indexes for the miUH. On D56, the PI was reduced in the miUH. The indexes depended on the week of pregnancy. EDN was present on the uterine arteries of all cats until D35, but disappeared by D49. The blood flow varied according to the category of horn.     

Correlation between the release of ovine trophoblast protein-1 by the conceptus and the production of polypeptides by the maternal endometrium of ewes

We studied the biosynthesis of two proteins, p70 (Mr 70,000; pI 4.0) and p15 (Mr 15,000; pI 5.7), by endometrial tissues from ewes between Days 12 and 24 of pregnancy and between Days 12 and 16 of the oestrous cycle to determine whether production of the two was correlated with the period of biosynthesis of ovine trophoblast protein-1 (oTP-1) by the conceptus. We also compared the protein synthetic activities of endometrium from gravid and non-gravid horns of pregnant ewes at Days 14, 16 and 18 in which the conceptus had been confined to one uterine horn. Proteins p70 and p15 were produced maximally between Days 14 and 20 of pregnancy, but synthesis by endometrial cultures from cyclic ewes was low or absent. Furthermore, synthesis of Protein p70 in particular was much greater by the gravid than non-gravid horn of unilaterally pregnant ewes. We conclude that synthesis of Proteins p70 and p15 by the uterus of sheep coincides with the time of oTP-1 production by the conceptus.     

Endothelial vasodilator production by uterine and systemic arteries. IV. Cyclooxygenase isoform expression during the ovarian cycle and pregnancy in sheep

Uterine artery endothelial production of the potent vasodilator, prostacyclin, is greater in pregnant versus nonpregnant sheep and in whole uterine artery from intact versus ovariectomized ewes. We hypothesized that uterine artery cyclooxygenase (COX)-1 and/or COX-2 expression would be elevated during pregnancy (high estrogen and progesterone) and the follicular phase of the ovarian cycle (high estrogen/low progesterone) as compared to that in luteal phase (low estrogen/high progesterone) or in ovariectomized (low estrogen and progesterone) ewes. Uterine and systemic (omental) arteries were obtained from nonpregnant luteal-phase (LUT; n = 10), follicular-phase (FOL; n = 11), and ovariectomized (OVEX; n = 10) sheep, as well as from pregnant sheep (110-130 days gestation; term = 145 +/- 3 days; n = 12). Endothelial and vascular smooth muscle (VSM) COX-1 protein levels and uterine artery endothelial cell COX-1 mRNA levels were compared. Using immunohistochemistry and Western analysis, the primary location of COX-1 protein was the endothelium; that is, we observed 2.2-fold higher COX-1 protein levels in intact versus endothelium-denuded uterine artery and a 6.1-fold higher expression in the endothelium versus VSM (P < 0.05). COX-2 protein expression was not detectable in either uterine artery endothelium or VSM. COX-1 protein levels were observed to be higher (1.5-fold those of LUT) in uterine artery endothelium from FOL versus either OVEX or LUT nonpregnant ewes (P < 0.05), with substantially higher COX-1 levels seen in pregnancy (4.8-fold those of LUT). Increases in uterine artery endothelial COX-1 protein were highly correlated to increases in the level of COX-1 mRNA (r(2) = 0.66; P < 0.01) for all treatment groups (n = 6-8 per group), suggesting that increased COX-1 protein levels are regulated at the level of increased COX-1 mRNA. No change in COX-1 expression was observed between groups in a systemic (omental) artery. In conclusion, COX-1 expression is specifically up-regulated in the uterine artery endothelium during high uterine blood flow states such as the follicular phase and, in particular, pregnancy.     

Cerebral oxygen consumption during asphyxia in fetal sheep

Cerebral blood flow and cerebral arteriovenous oxygen content difference were measured in 17 fetal sheep, and cerebral oxygen uptake was calculated. The measurements were made under control conditions and after profound fetal asphyxia induced of uterine blood flow for up to 90 min. In 14 of the fetal sheep, sequential measurements were made to examine hemodynamic changes and cerebral oxygen consumption at comparable intervals up to 36 min of asphyxia. These fetuses initially had elevated blood pressure and lowered heart rate became hypoxemic, hypercarbic, and acidotic. There was an initial decrease in cerebral oxygen consumption. Sequential measurements, however, showed a relative stability in this decreased oxygenation during 4 to 36 min of asphyxia despite a progressive metabolic acidosis. The cerebral fractional oxygen extraction remained unchanged despite a mean pH of 6.98 at 36 min. The calculated cerebral oxygen uptake during asphyxia in all 17 sheep was grouped according to whether the ascending aortic oxygen content was greater or less than 1.0 mmol/l. In the first group with mean ascending aortic oxygen content of 1.3 mmol/l, blood flow to the brain was increased and cerebral oxygen consumption was 85% of control. In the second group with mean arterial blood oxygen content of 0.8 mmol/l, there was a narrowing of the arteriovenous oxygen content difference, but no further increase in cerebral blood flow. Cerebral oxygen consumption was only 48% of control in this more asphyxiated group. We conclude that the degree of hypoxemia in the second group represents a point where physiologic mechanisms cannot compensate, and may be associated with neuronal damage.     

The effect of elevation of maternal plasma catecholamines on the fetus and placenta of the pregnant sheep

To study the effects of reduced uterine blood flow on fetal and placental metabolism, adrenaline has been infused at physiological doses (0.5 microgram/min per kg) into the circulation of the pregnant sheep. This gives a reduction of about one third of uterine blood flow at days 120-143 of pregnancy, but causes no significant change in umbilical blood flow. In contrast to the effects of constricting the uterine artery to reduce blood flow to a similar degree, placental oxygen consumption was reduced and that, together with a large increase in lactate production, indicated the placenta became hypoxic. The fetal blood gas status and hence oxygen consumption was not affected significantly. A consistent arterio-venous difference for glucose across the umbilical or uterine circulations was not detected unless the uterine blood flow was comparatively high. Glucose balance across the uterus showed a close linear relationship with uterine blood flow and more particularly with the supply of glucose to the uterus. There was clear evidence for glucose uptake by the placenta and fetus and also glucose output by both. The latter was more common when uterine blood flow was comparatively low or reduced by adrenaline infusion. The results are consistent with the concept that glucose supply has to be maintained to the placenta even at the expense of fetal stores, although lactate can substitute if there is enhanced output because of fetal hypoxia. They indicate that placental mobilisation of glycogen can lead to a net output of glucose to the mother. The manner of communicating to the fetus changes in placental state that occur during maternal adrenaline infusion is not clear. However towards the end of the 60 min infusion, elevation of fetal plasma adrenaline, probably resulting from a breakdown of the placental permeability barrier, may be an important signal.     

Role of the sympathetic innervation on uterine electromyographic activity in nonpregnant ovariectomized sheep under estrogen supplementation.

The aims of the present study were to characterize the sympathetic innervation of the nonpregnant sheep uterus, to determine the catecholamine content in myometrium (MYO) and endometrium, and to study the effects of chemical sympathectomy (CHSPX) on uterine catecholamine content and on uterine electromyographic (EMG) activity recorded from the MYO and mesometrium (MESO) in the nonpregnant ovariectomized sheep. After synchronization of estrus, 9 nonpregnant sheep were anesthetized with halothane, ovariectomized, and fitted with vascular catheters and EMG electrodes. Estradiol-17 beta was administered intravascularly at a rate of 50 micrograms/24 h for 10 days. CHSPX was induced with 6-hydroxy dopamine (20 mg/kg). Uterine tissues were obtained for determination of catecholamine content by HPLC and for immunocytochemical staining using an antibody against tyrosine hydroxylase (TH). In nonpregnant ovariectomized sheep, TH immunostaining was present in nerve fibers located in endometrium and MYO. In all layers of the uterus, catecholamine fibers were found in the proximity of blood vessels as well as in defined regions of the parenchyma. Throughout the uterus, norepinephrine content and TH immunostaining were dramatically decreased after CHSPX. CHSPX decreased uterine short EMG event activity in both MYO and MESO. Contracture-type activity was not affected in MYO and was increased in MESO. We conclude that sympathetic innervation modulates the MYO and MESO EMG activity in nonpregnant ovariectomized sheep under estradiol supplementation, and that the removal of the sympathetic innervation induces a decrease in the spontaneous activity.     

Sex ratio bias in postpartum-conceived Norway rat litters is produced by embryonic loss in midpregnancy

In rats, dams that conceive in their postpartum oestrus and then lose their firstborn litter bias the sex ratio of the litter toward females in utero. The present study identifies the source of litter sex ratio bias in these postpartum pregnant non-lactating dams. The female bias arises first through the postconception loss of embryos, and second, the loss occurs in midpregnancy between the attachment of the blastocyst to the uterine wall on day 5 and full metrial gland development on day 14. Some pregnancies were restricted to one uterine horn to see if this loss (and thus the opportunity for litter sex ratio biasing) was influenced by local factors operating within the uterine horn. Embryonic loss was more closely associated with the number of embryos implanting in a single horn than with the number implanting in the litter, demonstrating that local crowding within a horn is sufficient for the preferential loss of male embryos. This loss did not cause an obvious decrease in the size of the live-born litter because only those horns with a surfeit of embryos lost them. This process was the same in the right and left horns; both carried and lost the same numbers of embryos. A dam that conceives in her postpartum oestrus and then loses her suckling litter forgoes the implantation delay and uterine healing caused by lactation. Male embryos are less successful at implanting in a uterus only recently vacated by a previous litter.     

Effect of restriction of placental growth on oxygen delivery to and consumption by the pregnant uterus and fetus

Endometrial caruncles were excised from 13 sheep (caruncle sheep) before pregnancy to restrict placental growth. In subsequent pregnancies, half the caruncle fetuses were growth retarded or small (weight more than 2 SD below mean weight for control fetuses) with the remainder, normal-sized (weight within 2 SD of mean weight for control fetuses). The caruncle and 16 control sheep, each with indwelling vascular catheters, were studied between 121 and 130 days of pregnancy. Oxygen delivery to and consumption by the pregnant uterus in caruncle sheep with small fetuses was significantly reduced compared to controls while oxygen extraction was significantly increased. Oxygen tension (P02) and content in the common umbilical vein and in the descending aorta were significantly lower in small caruncle fetuses compared to controls but only P02 was lower in normal-sized caruncle fetuses. Oxygen delivery to, and consumption by, the fetus was significantly reduced in normal-sized and in small caruncle sheep compared to controls while oxygen extraction was increased in small caruncle sheep. Utero-placental oxygen consumption was significantly lower in caruncle sheep with small fetuses compared to that in controls. Despite these changes, oxygen consumption by the gravid uterus and fetus, per kg of tissue mass, was similar in both groups of caruncle and in control sheep. Utero-placental oxygen consumption per kg of utero-placental mass in caruncle sheep with small fetuses was not significantly different to that in sheep with normal-sized caruncle or control fetuses, although it averaged only 25% of that in controls. It is concluded that intrauterine growth retardation following restriction of placental growth is associated with a reduced supply of oxygen to both the pregnant uterus and fetus and a redistribution of oxygen to the fetus. This is due to the disproportionate maintenance of fetal growth relative to that of the placenta, since oxygen consumption by either, in terms of tissue mass, was not altered. Further, the greater uterine and fetal extraction of oxygen suggests that a smaller margin of safety may exist between supply and demand in intrauterine growth retardation.     

Unilateral luteotropic effect of uterine venous effluent of a gravid uterine horn in sheep.

The involvement of the main uterine vein in the unilateral maintenance of CL was studied in bilaterally ovulating unilaterally pregnant ewes. Ewes were mated at estrus (Day 0) and bilaterally ovulating ewes were randomized into three groups at surgery on Day 5. In all ewes, the uterine horns were separated through the intercornual area and one was ligated and transected near the internal bifurcation to produce a nongravid horn. One group served as controls (five ewes). In the other two groups the main uterine vein on one side was surgically anastomosed (end to side) to the corresponding vein of the opposite side (gravid side to nongravid side in one group--three ewes, and nongravid side to gravid side in the other--three ewes). Necropsies were done on Day 20. Mean CL weight was less, (P less than .01) on the nongravid side in control ewes than on the gravid side in control ewes or for either side in the other two groups. There were no significant differences among mean weights of CL on the gravid side in control ewes and either side in the other two groups. The CL regressed when the ipsilateral uterine vein contained blood from only the nongravid horn whereas the CL was maintained when the ipsilateral uterine vein contained venous blood from a gravid horn, whether or not it also contained blood from a nongravid horn. Results indicate that the uterine venous effluent from a gravid uterine horn in sheep has a luteotropic effect on the ipsilateral CL.     

Effect of high levels of insulin on glucose utilization and glucose production in pregnant and nonpregnant sheep

The present study was conducted to test the hypothesis that pregnancy in sheep alters the effects of insulin on glucose utilization and glucose production. Euglycemic, hyperinsulinemic glucose clamp experiments were performed in chronically catheterized, unstressed, fed or 24-hr fasted, nonpregnant sheep and fed, pregnant sheep. Endogenous glucose production rate for the whole sheep and glucose utilization rate of the uterine and nonuterine maternal tissues were measured in control and high-insulin periods by tracer technique using [6-3H]glucose. Control glucose utilization rate in the fed, nonpregnant sheep was significantly (P less than 0.05) greater than that in the fasted, nonpregnant sheep, 2.29 +/- 0.17 and 1.86 +/- 0.11 mg/min/kg, respectively, and also in the nonuterine maternal tissues of the pregnant sheep (1.71 +/- 0.18 mg/min/kg). Insulin stimulated glucose utilization 116.4 +/- 14.8% in the fed, nonpregnant sheep but only 82.8 +/- 11.0% in the fasted, nonpregnant sheep and 94.2 +/- 14.3% in the nonuterine tissues of the fed, pregnant sheep. Also, insulin suppressed endogenous glucose production to 53.2 +/- 5.6% in the fed, nonpregnant sheep, to 3.9 +/- 3.1% in the fasted, nonpregnant sheep, and to 9.0 +/- 3.7% in the fed, pregnant sheep. In the pregnant animals, uterine glucose uptake and uterine glucose utilization were not different and were not altered by changes in maternal insulin concentration. The results indicate that during late pregnancy glucose utilization is reduced and resistance to the effect of insulin to enhance glucose utilization is present in the nonuterine maternal tissues compared with nonpregnant, fed sheep. In contrast, the effectiveness of insulin to suppress glucose production in the pregnant sheep is greater than that in nonpregnant, fed sheep. These results also demonstrate that differential changes in the effect of insulin can exist simultaneously between peripheral (glucose consuming) and central (glucose producing) tissues. The changes in glucose utilization and in insulin effect in the pregnant sheep are both qualitatively and quantitatively similar to those of the nonpregnant sheep when fasted, suggesting that similar substrate and/or hormonal factors may be involved.     

Pregnancy-induced long-term uterine vascular remodeling in the rat

Despite the available research investigating uterine physiology during and immediately following pregnancy, including at the vascular and muscular levels, knowledge of the potential long-term timeline of such changes is limited. Thus, our study sought to investigate the potential long-term changes in uterine vasculature and horn length in the postpartum rat, following delivery and weaning. Female Long-Evans rats (n = 9–11 rats/group/timepoint) were divided into two groups: a pregnant group and an age-matched virgin control group. Rat weight, food consumption and vaginal impedance measurements were recorded throughout the experiment. Rats in the pregnant group were bred and pregnancy was confirmed using ultrasound imaging. The uterus and its vasculature were collected at various timepoints following weaning: 3 (week of weaning), 8–9 and 13 weeks postpartum, and at age-equivalent timepoints in the virgin group, and the diameters of the main uterine artery and vein, and lengths of the mesometrial segmental vessels (MSV) and uterine horns were recorded. The results indicated a significant difference between the previously-pregnant and virgin rats in both internal and external arterial diameters (but not arterial wall thickness), as well as the uterine horn length, 3 weeks postpartum, but not 8–9 and 13 weeks postpartum. Significant differences were observed in both venous diameter and MSV length at all timepoints measured. Placental scars were also observed in previously-pregnant rats at all timepoints measured. Our study highlights the long-term impact of pregnancy on the uterine vasculature and the necessity for consideration of such changes on subsequent pregnancies, as well as pregnancy-related vascular pathologies.     

Prostaglandins F in uterine and ovarian venous plasma from nonpregnant and pregnant ewes collected by cannulation.

Periodic collections of uterine venous blood were obtained from three nonmated, three pregnant and two mated but nonpregnant ewes in which uterine veins were cannulated with polyvinyl tubing on day 11 postestrus. Frequent sampling was achieved in three of these ewes with additional cannulae in the ovarian veins. Blood samples were collected at 3-hr intervals from 0600 on day 12 to 1800 on day 13 and then 6-hr intervals through day 15. On day 13, three additional samples at 30-min intervals were collected between 1400 and 1530. Prostaglandins F (PGF) in plasma were quantified by radioimmunoassay. On day 12, one ewe in each group had at least one measurement which suggested an increased rate of release of PGF into the uterine vein. Seven of eight ewes on day 13 appeared to have increased rates of release of PGF from the uterus between 0900 and 1500. The highest level measured in each ewe during this period ranged from 2.7 to 11 ng per milliliter. Concentrations of PGF in ovarian venous plasma in two of three ewes were positively correlated (P less than .05) with concentrations of PGF in uterine venous plasma (r equals .64 in each ewe). No evidence was obtained that pregnant and nonpregnant ewes differ in rate or pattern of release of PGF from the uterus into the uterine vein on days 12 and 13. Comparisons could not be made with confidence concerning PGF either in uterine veins on days 14 and 15 or in ovarian veins on all days due to limited number of observations.     

Plasma 13,14-dihydro-15-keto-PGF alpha (PGFM) in pregnant and nonpregnant heifers prior to and during surgery and following intrauterine injection of PGF2 alpha

On day 17 postestrus or postmating, heifers were given intrauterine injections of saline (2 pregnant, 2 non-pregnant) or 200 micrograms PGF2 alpha (7 pregnant, 6 nonpregnant) through cannulae installed surgically into the uterine horn ipsilateral to the corpus luteum bearing ovary. Jugular blood samples were collected prior to the laparotomy at which the cannulae were installed during surgery, and for 90 min following the intrauterine injection. Plasma was assayed for progesterone and 13,14-dihydro-15-keto-PGF2 alpha (PGFM). Laparotomies were reopened to confirm proper cannula placement and to determine if blastocysts were present in mated heifers. Concentrations of PGFM were higher in pregnant compared to nonpregnant heifers during the presurgery (68 +/- 26 vs 24 +/- 26 pg/ml; P less than .025) and surgery (186 +/- 47 vs 65 +/- 17 pg/ml; P less than .05) periods. Pregnancy status did not alter the mean concentrations of PGFM (pregnant, 554 +/- 70 pg/ml; nonpregnant, 422 +/- 81 pg/ml) or the half-life of its decline in concentration (18 min) following intrauterine injection of PGF2 alpha. Pregnancy at 17 days in cattle does not appear to influence PGF2 alpha transport from the uterine lumen or its metabolism in the uterus or elsewhere in response to an acute intrauterine injection.