Uterine Venous Blood Research Articles

Pelvic pain and venous congestion revisited: examining relationship between chronic pelvic pain and uterine venous size and blood flow.

To investigate the relationship between increased uterine venous plexus diameter and chronic pelvic pain in women attending a gynecology clinic. This was a retrospective study of patients attending a tertiary university hospital in London, UK. Women presenting to the gynecology clinic undergoing transvaginal ultrasound examination were recruited into the study. The largest trunk of the uterine venous plexus was measured on each side. Blood flow within the uterine veins was categorized into continuous or interrupted flow and evaluated using color and spectral Doppler ultrasound during normal respiration and on Valsalva maneuver to demonstrate the presence of venous reflux. The largest uterine vein diameter and its blood flow were used for the analysis. The main variables of interest were chronic pelvic pain, uterine vein diameter and type of blood flow. We included 1500 women in the study, of whom 584 (38.9% (95% CI, 36.5-41.5%)) reported chronic pelvic pain. Dysmenorrhea was the most common type of pelvic pain. Age (P < 0.001), menopausal status (P = 0.02), varicose veins (P = 0.01), adenomyosis (P < 0.001) and endometriosis (P < 0.001) were found to be independently associated with the occurrence of pain on multiple logistic regression analysis. There was no difference in uterine vein diameter between women with and those without pain (P = 0.10). Neither uterine vein diameter (P = 0.47) nor type of blood flow (P = 0.07) was significantly associated with the occurrence of pelvic pain on multiple logistic regression. Our findings show that uterine vein diameter is not associated with pelvic pain. However, we found other important clinical and demographic factors that are associated with chronic pelvic pain. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

PSII-34 Placental GLUT3 (SLC2A3) RNA interference: Impact on fetal growth at mid-gestation

Abstract Glucose is the predominant energy substrate for fetal oxidative processes and growth, and is taken up by the placenta and transported to the fetus by the facilitative transporters GLUT1 (SLC2A1) and GLUT3 (SLC2A3). SLC2A1 is the most abundant placental transporter, and as such is believed to be the primary glucose transporter in human and sheep placenta. However, SLC2A3 exhibits a six-fold greater glucose transport capacity, and in sheep, SLC2A3 is localized to the apical trophoblast membrane, whereas SLC2A1 is predominantly localized to the basolateral membrane, indicating that both may be required for optimal fetal development. It was our objective to use placenta-specific RNA interference (RNAi) to diminish SLC2A3, and determine the impact at mid-gestation (75 dGA) in sheep. Single hatched blastocysts were harvested and the trophectoderm was infected with lentiviral constructs expressing either a scramble control (SC) or SLC2A3-specific (GLUT3-RNAi) short-hairpin RNA, and then surgically transferred into a synchronized recipient. The resulting pregnancies underwent ultrasound Doppler velocimetry and fetal measurements at 70 dGA, and a terminal surgery at 75 dGA for collection of uterine and umbilical arterial and venous blood, fetal and placental measurements and tissue samples. Due to a lack of fetal sex x treatment interactions, statistical comparisons between SC (n = 6) and GLUT3-RNAi (n = 6) pregnancies were made by Student’s T-test. At 70 dGA, while umbilical artery velocimetry was not impacted, biparietal diameter (P ≤ 0.10), femur length and tibia length (P ≤ 0.05) were reduced in GLUT3-RNAi pregnancies. These results were confirmed at 75 dGA surgery, as GLUT3-RNAi fetuses had reduced fetal weight (P ≤ 0.10), head circumference (P ≤ 0.05), femur length (P ≤ 0.05), and tibia length (P ≤ 0.05). While it has been suggested that GLUT3 is predominantly important in late gestation, these preliminary data indicate that GLUT3 is important for normal fetal development during the first-half of gestation as well. Supported by NIH grant HD094952.

A data-driven model to study utero-ovarian blood flow physiology during pregnancy

In this paper, we describe a mathematical model of the cardiovascular system in human pregnancy. An automated, closed-loop 1D–0D modelling framework was developed, and we demonstrate its efficacy in (1) reproducing measured multi-variate cardiovascular variables (pulse pressure, total peripheral resistance and cardiac output) and (2) providing automated estimates of variables that have not been measured (uterine arterial and venous blood flow, pulse wave velocity, pulsatility index). This is the first model capable of estimating volumetric blood flow to the uterus via the utero-ovarian communicating arteries. It is also the first model capable of capturing wave propagation phenomena in the utero-ovarian circulation, which are important for the accurate estimation of arterial stiffness in contemporary obstetric practice. The model will provide a basis for future studies aiming to elucidate the physiological mechanisms underlying the dynamic properties (changing shapes) of vascular flow waveforms that are observed with advancing gestation. This in turn will facilitate the development of methods for the earlier detection of pathologies that have an influence on vascular structure and behaviour.

Prostaglandin E1 or E2 inhibits an oxytocin-induced premature luteolysis in ewes when oxytocin is given early in the estrous cycle

The objective of this study was to determine whether PGE1 or PGE2 prevents a premature luteolysis when oxytocin is given on Days 1 to 6 of the ovine estrous cycle. Oxytocin given into the jugular vein every 8 hours on Days 1 to 6 postestrus in ewes decreased (P ≤ 0.05) luteal weights on Day 8 postestrus. Plasma progesterone differed (P ≤ 0.05) among the treatment groups; toward the end of the experimental period, concentrations of circulating progesterone in the oxytocin-only treatment group decreased (P ≤ 0.05) when compared with the other treatment groups. Plasma progesterone concentrations in ewes receiving PGE1 or PGE1 + oxytocin were greater (P ≤ 0.05) than in vehicle controls or in ewes receiving PGE2 or PGE2 + oxytocin and was greater (P ≤ 0.05) in all treatment groups receiving PGE1 or PGE2 than in ewes treated only with oxytocin. Chronic intrauterine treatment with PGE1 or PGE2 also prevented (P ≤ 0.05) oxytocin decreases in luteal unoccupied and occupied LH receptors on Day 8 postestrus. Oxytocin given alone on Days 1 to 6 postestrus in ewes advanced (P ≤ 0.05) increases in PGF2α in inferior vena cava or uterine venous blood. PGE1 or PGE2 given alone did not affect (P ≥ 0.05) concentrations of PGF2α in inferior vena cava and uterine venous blood when compared with vehicle controls or oxytocin-induced PGF2α increases (P ≤ 0.05) in inferior vena cava or uterine venous blood. We concluded that PGE1 or PGE2 prevented oxytocin-induced premature luteolysis by preventing a loss of luteal unoccupied and occupied LH receptors.

Relationship Between Contractions of the Uterus and Concentration of PGF2α in Uterine Venous Blood after Luteolysis in Gilts

The origin and physiological significance of high pulses of prostaglandin F2α (PGF2α) in uterine venous blood that occur 2-3 days after luteolysis are not well understood. We studied the relationship between contractions of the uterus evoked by exogenous oxytocin (OT) and PGF2α concentration in uterine venous blood on day 17 of the porcine oestrous cycle. The infusion of OT into the uterine artery produced an immediate increase in the uterine intraluminal pressure (UIP) (p < 0.001) and a simultaneous elevation in PGF2α concentration in uterine venous blood (p < 0.0001). The infusion of indomethacin (IND) into the uterine artery slightly decreased PGF2α concentration in uterine venous blood, but it did not suppress uterine contraction or the rapid increase in PGF2α concentration in uterine venous blood just after OT infusion (p < 0.0001), which was lower that in gilts not treated with IND. We conclude that the spikes of PGF2α concentration in uterine venous blood occurring after OT infusion on day 17 of the porcine oestrous cycle are mainly caused by the excretion with venous blood from the remodelled uterus and that PGF2α synthesis may contribute to this. These results suggest that the high spikes in PGF2α concentration that occur 2-3 days after luteolysis in pigs, sheep, cows and mares all have a similar origin.

Transport of Prostaglandin F2α Pulses from the Uterus to the Ovary at the Time of Luteolysis in Ruminants Is Regulated by Prostaglandin Transporter-Mediated Mechanisms

In ruminants, prostaglandin F2alpha (PGF(2alpha)) is the uterine luteolytic hormone. During luteolysis, PGF(2alpha) is synthesized and released from the endometrium in a pulsatile pattern. The unique structure of the vascular utero-ovarian plexus (UOP) allows transport of luteolytic PGF(2alpha) pulses directly from the uterus to the ovary, thus bypassing the systemic circulation. However, the underlying molecular mechanism is not known. The objective of the present study was to determine a role for PG transporter protein (PGT) in the compartmental transport of PGF(2alpha) from uterus to ovary through the UOP at the time of luteolysis using the sheep as a ruminant model. [(3)H]PGF(2alpha), with or without a PGT inhibitor, was infused into UOP, and PGF(2alpha) transport and PGT protein expression were determined. Results indicate that PGT protein is expressed in tunica intima, tunica media, and tunica adventitia of the utero-ovarian vein and the ovarian artery of the UOP, and the expression levels are higher on d 10-15 compared with d 3-6 of the estrous cycle. Pharmacological inhibition of PGT prevented transport of exogenous [(3)H]PGF(2alpha) as well as oxytocin-induced endogenous luteolytic PGF(2alpha) pulse up to 80% from uterine venous blood into ovarian arterial blood through the UOP at the time of luteolysis in sheep. Taken together, these results indicate that at the time of luteolysis, transport of PGF(2alpha) from uterus to ovary through the UOP is regulated by PGT-mediated mechanisms. These findings also suggest that impaired PGT-mediated transport of PGF(2alpha) from the utero-ovarian vein into the ovarian artery could adversely influence luteolysis and thus affect fertility in ruminants.

Uterine venous blood flow in normal and complicated pregnancies: a methodological study

To investigate the possibility of recording Doppler flow signals from the maternal uterine veins (UtVs) during pregnancy and to assess the relationship between UtV signals and other Doppler parameters as well as pregnancy outcomes. Transabdominal Doppler ultrasound examination of the UtVs on both sides of the uterus was performed in 40 normal and 44 high-risk singleton pregnancies at 23-39 weeks' gestation. The UtV was identified using color Doppler imaging and the flow velocity signals of the UtV and uterine artery (UtA) were recorded. Morphological examination of the placenta was carried out in 45 of the pregnancies (14 uncomplicated and 31 high-risk pregnancies). Flow-velocity signals of the UtVs were recorded from at least one side of the uterus in all patients (success rate of 81 and 89% for the right and left UtV, respectively). Three types of flow-velocity pattern were identified: continuous non-pulsatile flow (Type I, n = 70), pulsatile flow with a notch touching the zero line (Type II, n = 6) and pulsatile flow with absent flow signals for part of the heart cycle (Type III, n = 8). The UtA pulsatility index was significantly higher in women with UtV Types II and III than in those with UtV Type I (P = 0.039). Similarly, UtV Types II and III were more often found in pregnancies with bilateral UtA notching (P = 0.013) and with UtA score 3-4 (P = 0.024) than in those with normal UtA. No statistically significant association was found between the UtV flow pattern and abnormal histopathological findings in the placenta, or between the UtV and umbilical artery findings. It is possible to record Doppler signals from the UtVs in the late second and third trimesters of pregnancy. Pulsatile flow-velocity patterns of the UtVs are associated with abnormal UtA Doppler findings.

Prostaglandin E 1 (PGE 1), but not prostaglandin E 2 (PGE 2), alters luteal and endometrial luteinizing hormone (LH) occupied and unoccupied LH receptors and mRNA for LH receptors in ovine luteal tissue to prevent luteolysis

Loss of luteal progesterone secretion at the end of the ovine estrous cycle is via uterine PGF 2α secretion. However, uterine PGF 2α secretion is not decreased during early pregnancy in ewes. Instead, the embryo imparts a resistance to PGF 2α. Prostaglandins E (PGE; PGE 1 + PGE 2) are increased in endometrium and uterine venous blood during early pregnancy in ewes to prevent luteolysis. Chronic intrauterine infusion of PGE 1 or PGE 2 prevents spontaneous or IUD, estradiol-17β, or PGF 2α-induced premature luteolysis in nonbred ewes. The objective was to determine whether chronic intrauterine infusion of PGE 1 or PGE 2 affected mRNA for LH receptors, occupied and unoccupied receptors for LH in luteal and caruncular endometrium, and luteal function. Ewes received Vehicle, PGE 1, or PGE 2 every 4 h from days 10 to 16 of the estrous cycle via a cathether installed in the uterine lumen ipsilateral to the luteal-containing ovary. Jugular venous blood was collected daily for analysis of progesterone and uterine venous blood was collected on day-16 for analysis of PGF 2α and PGE. Corpora lutea and caruncular endometrium were collected from day-10 preluteolytic control ewes and day-16 ewes treated with Vehicle, PGE 1 or PGE 2 for analysis of the mRNA for LH receptors and occupied and unoccupied receptors for LH. Luteal weights on day-16 in ewes treated with PGE 1 or PGE 2 and day-10 control ewes were similar ( P ≥ 0.05), but were greater ( P ≤ 0.05) than in day-16 Vehicle-treated ewes. Progesterone profiles on days 10–16 differed ( P ≤ 0.05) among treatment groups: PGE 1 > PGE 2 > Vehicle-treated ewes. Concentrations of PGF 2α and PGE in uterine venous plasma on day-16 were similar ( P ≥ 0.05) in the three treatment groups. Luteal mRNA for LH receptors and unoccupied and occupied LH receptors were similar ( P ≥ 0.05) in day-10 control ewes and day-16 ewes treated with PGE 2 and were lower ( P ≤ 0.05) in day-16 Vehicle-treated ewes. PGE 2 prevented loss ( P ≤ 0.05) of day-16 luteal mRNA for LH receptors and occupied and unoccupied LH receptors. Luteal and caruncular tissue mRNA for LH receptors and occupied and unoccupied LH receptors were greater ( P ≤ 0.05) on day-16 of PGE 1-treated ewes than any treatment group. mRNA for LH receptors and occupied and unoccupied receptors for LH in caruncules were greater ( P ≤ 0.05) in day-16 Vehicle or PGE 2-treated ewes than in day-10 control ewes. It is concluded that PGE 1 and PGE 2 share some common mechanisms to prevent luteolysis; however, only PGE 1 increased luteal and endometrial mRNA for LH receptors and occupied and unoccupied LH receptors. PGE 2 prevents a decrease in luteal mRNA for LH receptors and occupied and unoccupied receptors for LH without altering endometrial mRNA for LH receptors or occupied and unoccupied receptors for LH.

The Role of the Ovary for the Maintenance of Pregnancy in Cats

Plasma progesterone (P(4)) concentrations are maintained in pregnant cats until parturition, but become low in pseudopregnant cats 40-45 days after infertile mating. This difference in P(4) concentrations is considered to be due to P(4) secretion by the placenta of pregnant cats. Therefore, to clarify these points, we performed ovariectomy (OVX) at various stages of pregnancy, examined the pregnancy status and measured LH and P(4) concentrations in peripheral, ovarian and uterine venous blood. After OVX, abortion occurred in 100% (5/5), 80% (4/5), 40% (2/5) and 60% (3/5) of Groups I (Day 35), II (Day 40), III (Day 45) and IV (Day 50) cats, respectively. In the remaining cats, normal delivery took place on days 63-69 [mean, 66.1 +/- 1.1 (SE)] of pregnancy. The time to abortion after OVX was 4-8 (mean, 5.6 +/- 0.8), 3-17 (mean, 8.0 +/- 3.6), 10 and 11, and 2-4 (mean, 3.0 +/- 0.7) days in Groups I, II, III and IV, respectively. The plasma P(4) concentrations were 1-2 ng/ml in all groups on the day after OVX, decreasing to less than 1 ng/ml from the 2nd day onwards. The concentrations of P(4) in ovarian venous blood at the time of OVX decreased with the stage of pregnancy, but were clearly higher than those in peripheral blood. The plasma P(4) concentrations in uterine venous blood were similar to those in peripheral blood. These results suggest that peripheral P(4) in pregnant cats is the result of P(4) secretion secreted only by the ovarian corpus luteum, not by the placenta, but indicate that either P(4) is not essential for the maintenance of pregnancy in cats from day 40-45 of pregnancy onwards, or that the placenta provides a local source of P(4) that does not appear in measurable amounts in the peripheral circulation.

Transplantation of the uterus in sheep: Methodology and early reperfusion events

Uterine transplantation is developing into a clinical treatment for uterine factor infertility. An animal model with a similar uterus size and vessels to humans and with pregnancy extending over several months would be beneficial for research on uterine transplantation. The aim of this study was to develop and evaluate autotransplantation of the sheep uterus to an orthotopic position in the pelvis. Female sheep (n=7) were subjected to laparotomy with the uterus and its vascular supply and drainage being surgically isolated. The excised uterus was kept ex vivo at +4 degrees C for 60 min and then autotransplanted with vascular end-to-side anastomoses to the external iliac vessels. The effects of uterine blood-reperfusion were assessed by measurements of pCO(2), pO(2), lactate and pH in uterine venous blood. Uterine contractility and histology was assessed after 3 h of reperfusion. Reperfusion of blood was observed in five out of seven transplanted uteri. The pCO(2)/pO(2)-ratio and the lactate level were initially elevated but decreased and became normal after 60 min. After 3 h of reperfusion there was a visible tissue blood flow and spontaneous uterine contractions were seen. Histological analysis revealed a mild inflammation, but no edema or stasis. This study demonstrates that the sheep uterus can successfully be autotransplanted to an orthotopic position with novel vascular connections. This model is suitable for future experiments studying long-term results concerning uterine viability and pregnancy using a transplanted uterus of similar size to the human uterus.

Expression of Interferon (IFN)-Stimulated Genes in Extrauterine Tissues during Early Pregnancy in Sheep Is the Consequence of Endocrine IFN-τ Release from the Uterine Vein

The ruminant conceptus synthesizes and secretes interferon (IFN)-tau, which presumably acts via an intrauterine paracrine mechanism to signal maternal recognition of pregnancy. The aims of this study were to determine whether IFN-stimulated genes (ISG) such as ISG15 and OAS-1 are differentially expressed in blood cells circulating in the uterus of ewes; whether extrauterine components of the reproductive tract such as the corpus luteum (CL) also express mRNA for these ISG, and whether antiviral activity is greater in uterine vein than in uterine artery during early pregnancy. The concentrations of mRNA for both ISG were significantly greater (P < 0.0001) in endometrium and jugular blood of 15-d pregnant ewes than in nonpregnant ewes. ISG15 and OAS-1 mRNA concentrations were also greater (P < 0.05) in CL from 15-d pregnant ewes than in nonpregnant ewes. Immunohistochemistry revealed intense staining for ISG15 in large luteal cells on d 15 of pregnancy. Blood cells from uterine artery and vein of 15-d pregnant ewes had similar ISG15 and OAS-1 mRNA concentrations, suggesting that these cells were not conditioned by IFN-tau within the uterus. By using an antiviral assay, uterine venous blood was found to contain 500- to 1000-fold higher concentrations of bioactive IFN-tau than in uterine arterial blood on d 15 of pregnancy. It is concluded that uterine vein releases IFN-tau, which induces ISG in extrauterine tissues such as the CL during the time of maternal recognition of pregnancy.

Transplantation of the uterus in the sheep: oxidative stress and reperfusion injury after short-time cold storage

To study the effects of cold ischemia and reperfusion after transplantation of the sheep uterus and to compare the preservation solution Perfadex (Vitrolife, Mölndal, Sweden) with Ringer's acetate. Experimental animal study. University hospital. Adult, female sheep. One uterine horn with the common uterine cavity and cervix of sexually mature ewes was auto-transplanted after 1 hour of cold ischemic storage in either Perfadex (n = 5) or Ringer's acetate (n = 5). During 3 hours of reperfusion, uterine venous blood was collected and analyzed for several parameters that were indicative of oxidative stress and reperfusion injury. A biopsy was taken for histological analysis at the end of the experiment. Lipid peroxidation and ascorbyl radicals in uterine venous blood during reperfusion. Light microscopy and quantification of neutrophils in tissue after 3 hours of reperfusion. A decline in pH and a rise in lactate and pCO(2)-pO(2), as well as an elevation of antioxidant capacity, lipid peroxidation, and intensity of ascorbyl radical electron spin resonance signal, was found that was more prominent after storage in Ringer's acetate. The histological analysis revealed mild inflammation in both study groups. Short-time cold ischemic storage of the sheep uterus does not induce any severe reperfusion damage, but the use of the protective buffer Perfadex decreases oxidative stress and inflammation when compared with a more simple solution.

Do calcium-mediated cellular signalling pathways, prostaglandin E 2 (PGE 2), estrogen or progesterone receptor antagonists, or bacterial endotoxins affect bovine placental function in vitro?

The major objective of this experiment was to determine whether the bovine placenta could be stimulated to secrete progesterone, since the bovine placenta secretes little progesterone when the corpus luteum is functional. Secondly, we wanted to determine whether reported abortifacients or progesterone or estrogen receptor antagonists affected bovine placental prostaglandin secretion. The ovine placenta secretes half of the circulating progesterone at day 90 of pregnancy and PGE 2 appears to regulate ovine placental progesterone secretion. Calcium has been reported to regulate placental progesterone secretion in cattle. Diced 186–245-day placental slice explants from six Brahman and six Angus cows were incubated in vitro at 39.5 °C under 95% air: 5% CO 2 at pH 7.2 in 5 ml of M-199 for 1 h in the absence of treatments and for 4 and 8 h in the presence of treatments. Treatments were: vehicle; R24571; compound 48/80; IP 3; PGE 2; CaCl 2; cyclosporin A; lipopolysaccharide (endotoxin) from Salmonella abortus equi., enteriditis, and typhimurium; monensin; ionomycin; arachidonic acid; mimosine; palmitic acid; progesterone, androstenedione; estradiol-17β; A23187; RU-486; or MER-25. Jugular and uterine venous plasma and culture media were analyzed for progesterone, PGE 2 and PGF 2α by radioimmunoassay (RIA). Plasma hormone data were analyzed by a One-Way Analysis of Variance (ANOVA). Hormone data in culture media were analyzed for breed and treatment effects by a Factorial Design (2 breeds, 2-range of days, 21 treatments) for ANOVA (2 × 2 × 21). Since hormone data secreted by placental tissue in vitro did not differ ( P≥0.05) by breed or range of days of pregnancy, data were pooled and analyzed by a One-Way ANOVA. Concentrations of PGE 2 in uterine venous blood were two-fold greater ( P≤0.05) in Angus than Brahman cows. PGE 2 and PGF 2α in vehicle controls increased from 4 to 8 h ( P≤0.05), but not progesterone ( P≥0.05). Progesterone in culture media treated with RU-486 increased ( P≤0.05) at 4 and 8 h compared to vehicle controls and was not affected by other treatments ( P≥0.05). Concentrations of PGE 2 in media at 4 and 8 h were lower ( P≤0.05) when compared to controls except treatment with PGE 2 at 4 and 8 h and RU-486 at 8 h ( P≥0.05). PGF 2α was increased ( P≤0.05) by RU-486 at 8 h and no other treatment affected PGF 2α at 4 or 8 h ( P≤0.05). In conclusion, modulators of cellular calcium signalling pathways given alone do not affect bovine placental progesterone secretion at the days studied and progesterone receptor-mediated events appear to suppress placental progesterone, PGF 2α, and PGE 2 secretion in cattle. In addition, PGE 2 does not appear to regulate bovine placental progesterone secretion when the corpus luteum is functional and bacterial endotoxin does not appear to affect bovine placental secretion of PGF 2α or PGE 2.

The oestrous cycle and early pregnancy – a new concept of local endocrine regulation

Facts discovered in recent decades have compelled us to revise long-established views on the physiological regulation of cyclic adjustments to the reproductive system in preparation for pregnancy in females. Evidence has been presented to show that changes in the uterine blood supply induced by the oestrogen/progesterone ratio in the blood and cytokines are important in the regulation of the secretory function of the endometrium. Progressive reduction in uterine blood flow during the luteal phase of the oestrous cycle causes regressive changes in endometrial cells and release of prostaglandin (PG) F 2α, resulting in initiation of luteolysis. Retrograde transfer of PGF 2α in the area of the mesometrium vasculature is an important element in the mechanism protecting the corpora lutea against luteolysis before day 12 of the porcine oestrous cycle and during early pregnancy and pseudopregnancy. Results of many studies presented in this review indicate that PGF 2α pulses in uterine venous blood during the follicular phase of the oestrous cycle may not be due to PGF 2α secretion by endometrial cells, but occur due to remodeling of the endometrium and pulsatile exretion of PGF 2α in accordance with rhythmic uterine contractions caused by oxytocin.

Neurokinin B peptide serum levels are higher in normotensive pregnant women than in preeclamptic pregnant women

Objectives The purpose of this study was to examine neurokinin B levels in serum from preeclamptic and normotensive and to investigate the role of neurokinin B in preeclampsia. Study design Peripheral and uterine venous blood neurokinin B levels were measured in 14 normotensive and 8 preeclamptic pregnant women by radioimmunoassay. Results Neurokinin B levels in normotensive women were 4.91 ± 2.67 nmol/L in peripheral and 5.59 ± 2.06 nmol/L in uterine blood. In pregnant women with preeclampsia, neurokinin B levels were 2.79 ± 1.68 nmol/L and 3.20 ± 1.55 nmol/L, respectively. Neurokinin B levels were significantly higher in normotensive women ( P = .032 in peripheral and P = .006 in uterine blood). Conclusions Neurokinin B serum levels were higher in normotensive women. Higher neurokinin B concentrations in normotensive pregnant women may be due to the advanced gestational age and/or the result of a negative interaction of other vasoactive substances. The role of neurokinin B in preeclampsia remains to be determined.

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.

Uterine responses to exogenous oxytocin before and after pre-partum luteolysis in the cow.

The aim of this study was to test the functional status of uterine oxytocin receptors in cows in vivo around parturition. The animals received consecutive, intra-arterial injections of 800, 1,600 and 3,200 mU of oxytocin at three different stages: during late gestation (days 260-274), at 12 h and at 24 h after intramuscular injection of a prostaglandin F2alpha analogue at day 275 to induce parturition. Cows (n = 6) had been provided with myometrial electrodes and a catheter had been installed in the aorta and in a branch of the uterine vein (UV). Regular blood samples were obtained from the UV from 5 min before until 45 min after each oxytocin injection to measure plasma levels of prostaglandin F2alpha (PGF2alpha) and oxytocin. Uterine electromyographic (EMG) activity was registered continuously during each experiment. The increase of oxytocin levels in UV plasma after intra-arterial injections was dose dependent (p < 0.02). Pre- and post treatment oxytocin levels at 24 h after induction of parturition were significantly increased (p = 0.0313). Both during late pregnancy and at 12 h after induction of parturition, oxytocin caused a significant increase in EMG activity (p = 0.022). After the 3,200 mU dose the increase was significantly higher than with the other 2 doses (p = 0.004). After each dose, EMG activity returned to baseline levels within some 15 min. At 24 h after induction of parturition, the pre-treatment level of EMG activity had increased. Doses of 800 mU and 1,600 mU of oxytocin produced a significant (p = 0.022) increment of EMG activity, which was of the same magnitude as during the preceding stages; after 3,200 mU of oxytocin the response was significantly higher than before (p = 0.008). No significant increases of PGF2alpha levels in UV plasma could be measured after oxytocin injections at any of the three stages. It is concluded that the myometrium of the pregnant cow responds in vivo to physiological doses of oxytocin. At 24 h after induction of parturition, when luteolysis has occurred and a parturient pattern of parturient myometrial activity has already started to develop, the response is enhanced. Physiological doses of oxytocin did not evoke a spurt release of PGF2alpha in uterine venous blood during the peripartal period.

Effect of prostaglandin F 2α (PGF 2α), indomethacin, tamoxifen or estradiol-17β on prostaglandin E (PGE), PGF 2α and estradiol-17β secretion in 88 to 90-day pregnant sheep☆

Treatment with PGF 2α plus estradiol-17β aborts 90-day pregnant ewes, whereas PGF 2α or estradiol-17β alone does not abort ewes. The objective of this experiment was to evaluate whether tamoxifen, an estrogen receptor antagonist, estradiol-17β, prostaglandin F 2α (PGF 2α), indomethacin, or some of their interactions affected ovine uterine/placental secretion of PGF 2α, estradiol-17β or prostaglandins E (PGE), because a single treatment with PGF 2α and estradiol-17β given every 6 h aborts 90-day pregnant ewes. Concentrations of PGF 2α in uterine venous blood were increased ( P ≤ 0.05) by estradiol-17β, PGF 2α + estradiol-17β, and PGF 2α + tamoxifen, and decreased ( P ≤ 0.05) by indomethacin or PGF 2α + indomethacin at 72 h when compared to the 0 h samples. Concentrations of PGE in uterine venous blood were decreased ( P ≤ 0.05) by indomethacin and PGF 2α + indomethacin and increased ( P ≤ 0.05) by PGF 2α + estradiol-17β at 72 h when compared to the 0 h samples. Concentrations of PGF 2α in inferior vena cava blood at 6 h were increased ( P ≤ 0.05) by PGF 2α either alone or in combination with indomethacin, tamoxifen, or estradiol-17β, which is due to the PGF 2α injected. Concentrations of PGF 2α in inferior vena cava blood in PGF 2α + estradiol-17β-treated 88- to 90-day pregnant ewes increased ( P ≤ 0.05) linearly over the 72-h sampling period and averaged 4.0 + 0.4 ng/ml. Concentrations of PGF 2α in inferior vena cava blood of control, PGF 2α, tamoxifen, PGF 2α + indomethacin, PGF 2α + tamoxifen, and estradiol-17β-treated ewes did not differ ( P ≥ 0.05) and averaged 0.4 + 0.04 ng/ml. Profiles of PGE in inferior vena cava blood of 88- to 90-day pregnant ewes treated with vehicle, PGF 2α, estradiol-17β, tamoxifen, tamoxifen + PGF 2α, or estradiol-17β + PGF 2α did not differ ( P ≥ 0.05). Concentrations of PGE in inferior vena cava blood of 88- to 90-day pregnant ewes treated with indomethacin or PGF 2α + indomethacin were lower ( P ≤ 0.05) than in control ewes. Concentrations of estradiol-17β in jugular venous plasma of PGF 2α + estradiol-17β-treated 88- to 90-day pregnant ewes increased linearly and differed ( P ≤ 0.05) from controls. Profiles of estradiol-17β in jugular venous plasma of PGF 2α, indomethacin, tamoxifen, and PGF 2α + tamoxifen and PGF 2α + indomethacin, estradiol-17β, and controls did not differ ( P ≥ 0.05). It is concluded that treatment with a single injection of PGF 2α and estradiol-17β given every 6 h causes a linear increase in PGF 2α and estradiol-17β.

Effect of PGF 2α, indomethacin, tamoxifen, or estradiol-17β on incidence of abortion, progesterone, and pregnancy-specific protein B (PSPB) secretion in 88- to 90-day pregnant sheep☆

One objective of this experiment was to evaluate our hypotheses that estradiol-17β regulates secretion of pregnancy specific protein B (PSPB) and that secretion of progesterone during pregnancy is regulated by a prostanoid by examining the effects of prostaglandin F 2α (PGF 2α), a luteolyic agent; indomethacin, a prostanoid synthesis inhibitor; tamoxifen, an estrogen receptor antagonist; estradiol 17-β; and interaction of these factors on the incidence of abortion and progesterone and PSPB secretion. Another objective was to determine if there is a luteal source of PSPB. Weights of corpora lutea were decreased ( P ≤ 0.05) by PGF 2α, indomethacin, PGF 2α + tamoxifen, PGF 2α + indomethacin, and PGF 2α + estradiol-17β but not ( P ≥ 0.05) by tamoxifen or estradiol-17β alone. No ewe treated with PGF 2α alone aborted ( P ≥ 0.05). Forty percent of ewes treated with PGF 2α + estradiol-17β aborted ( P ≤ 0.05), but ewes were not aborted by any other treatment within the 72-h sampling period. Profiles of progesterone in jugular venous blood differed ( P ≤ 0.05) among control, indomethacin-, tamoxifen-, and PGF 2α + indomethacin-treated ewes. Progesterone in jugular venous blood of control ewes decreased ( P ≤ 0.05) by 24 h, followed by a quadratic increase ( P ≤ 0.05) from 24 to 62 h. Progesterone in jugular venous blood of indomethacin-, PGF 2α-, PGF 2α + tamoxifen-, PGF 2α + indomethacin-, PGF 2α + estradiol-17β-, and tamoxifen-treated ewes was reduced ( P ≤ 0.05) by 18 h and did not vary ( P ≥ 0.05) for the remainder of the 72-h sampling period. Progesterone in vena cava and in uterine venous blood was reduced ( P ≤ 0.05) at 72 h in PGF 2α-, indomethacin-, tamoxifen-, PGF 2α + indomethacin-, PGF 2α + tamoxifen-, and PGF 2α + estradiol-17β-treated ewes. Weights of placentomes did not differ among treatment groups ( P ≥ 0.05). Profiles of PSPB in inferior vena cava blood differed ( P ≤ 0.05) among control, estradiol-17β-, indomethacin-, tamoxifen-, PGF 2α + indomethacin-, and PGF 2α + tamoxifen-treated 88- to 90-day pregnant ewes. Concentrations of PSPB in inferior vena cava blood were increased ( P ≤ 0.05) in indomethacin-, estradiol-17β-, tamoxifen-, PGF 2α + tamoxifen-, and PGF 2α + indomethacin-treated 88- to 90-day pregnant ewes within 6 h and did not vary ( P ≥ 0.05) for the remainder of the 72-h sampling period. Concentrations of PSPB in uterine venous blood of indomethacin-, tamoxifen-, PGF 2α + tamoxifen-, and PGF 2α + indomethacin-treated ewes were greater ( P ≤ 0.05) at 72 h than at 0 h. PSPB in ovarian venous blood did not differ ( P ≥ 0.05) adjacent or opposite to the ovary with the corpus luteum. It is concluded from these data that estrogen regulates placental secretion of PSPB and that a prostanoid, presumably prostaglandin E, regulates placental secretion of progesterone during 88–90 days of gestation in sheep and that there is no luteal source of PSPB.

Contributions of endogenous inhibin and estradiol to the regulation of follicle-stimulating hormone and luteinizing hormone secretion in the pregnant rat.

To examine the contributions of endogenous inhibin and estradiol to the regulation of FSH and LH secretion in the pregnant rat, some rats were passively immunized against inhibin and/or estradiol, and others were ovariectomized, on Days 5, 10, 15, and 20 of pregnancy. Ovarian and uterine venous blood was collected separately to confirm the sources of inhibin and steroid hormones during pregnancy. Immunoreactivity of inhibin in the placenta was also examined by RIA. Levels of inhibin in ovarian venous plasma were significantly higher than those in peripheral plasma during pregnancy. No difference was observed between the levels of inhibin in uterine venous plasma and peripheral plasma. No immunoreactivity of inhibin was detected in placental homogenate from rats at Days 10, 15, and 20. FSH secretion significantly increased after immunoneutralization of inhibin during pregnancy. A marked increase in FSH secretion was noted on Days 5 and 20, and the smallest increase was observed on Day 15. Administration of estradiol antiserum (AS) alone did not induce a significant increase in FSH secretion on any day of pregnancy. However, a synergistic effect of estradiol AS and inhibin AS was observed on Day 20. On Days 5, 10, and 20, administration of inhibin AS or estradiol AS induced a significant increase in LH secretion. A synergistic effect of inhibin AS and estradiol AS on LH secretion was observed on Day 5. On Days 5 and 10, significantly high LH secretion was noted in ovariectomized rats as compared with that in rats treated with both inhibin AS and estradiol AS, indicating that other ovarian hormones such as progesterone may be involved in the suppression of LH secretion in these stages of pregnancy. These data indicate that both inhibin and estradiol, predominantly secreted from the ovary, are involved in the regulation of gonadotropin secretion during pregnancy as during the estrous cycle in the rat.