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[Acute reduction of uterine blood flow and fetal heart rate changes in pregnant sheep near term].

Five merino sheep near term were used for acute preparations to investigate the influence of basal uterine blood flow (UBF), basal fetal oxygenation and basal fetal heart rate (FHR) on FHR changes elicited by acute reduction of UBF. The ewes were anaesthesized with pentobarbital and Alloferin was given for relaxation. Ventilation was maintained via a tracheal tube by a Starling pump. Maternal heart rate, arterial pressure and intrauterine pressure as well as fetal heart rate and umbilical artery pressure were recorded continously. Initially blood flow was recorded by cuff flow meter sequentially in both uterine arteries for a short time in order to determine total UBF and the ratio of flows. During the UBF reduction sequence flow was recorded in the artery of the gravid horn continously and measurement was corrected according to the initial ratio of flows in both arteries, presuming that this ratio would remain constant throughout the course of the experiment. Repetitive and progressive acute reduction of UBF (approximately 25%, 50% and 100% from basal UBF value) was achieved three times, lasting 120 sec each and each approximatly 12 min apart, by flow meter controlled partial or total occlusion of the aorta abdominalis of the ewe with a balloon catheter inserted into the aorta. (In some cases the lateral abdominal section was left open and the aorta was compressed manually). Before, 90 sec after the beginning and 10 min after the end of UBF reduction blood samples were taken from the fetal catheters (Fig. 3). In two preparations this sequence was repeated once after complete recovery of FHR.

Animals↗

Establishment of a simple method for measurement of chronic blood flow in uterine artery of pregnant cows.

Blood flow to the gravid uterine horn of seven multiparous Holstein cows (mean +/- SD, BW = 625.5 +/- 82.4 kg; age = 4.7 +/- 1.7 yr; parity = 2.9 +/- 1.1 yr) was measured from d 225 of gestation to parturition using transit-time ultrasonic blood flow probes placed around the middle uterine artery. Surgery was conducted on d 215 of gestation. The cows were sedated with xylazine and local anesthesia (procaine or bupivacain hydrochloride) during surgery. The surgical operations were conducted at the flank of standing cows. A transit time ultrasonic flow probe ("S" series, diameter 12 or 14 mm, Transonic Systems Inc., Ithaca, NY) was fitted surgically around the uterine artery of each cow. Surgery was completed within 2 h of anesthesia, and the animals recovered rapidly following surgery. Uterine blood flow (UBF, L/min) was recorded at 10-s intervals for 1395 min; these values were averaged to determine UBF. Cows exhibited normal gestation lengths (279.1 +/- 7.4 d), gave birth to normal healthy calves (birth weight = 40.6 +/- 6.6 kg), and had no retained placentas. The UBF increased significantly (P < 0.01) from d 225 (6.67 +/- 2.47) to d 249 (8.23 +/- 2.89) of gestation, but the latter UBF was similar to that of d 266 (8.38 +/- 2.70). The increased UBF after d 225 indicates increased demand of nutrients of fetus with the progress of gestation. The range of mean UBF varied widely among individual cows from 4.1 L/min to 12.2 L/min. Our method is useful for chronic measurement of UBF in cows for nutritional or physiological studies and does not require sophisticated facilities or special surgical technique.

Animals↗

Stage-dependent fetal umbilical blood flow changes induced by laser therapy and amniodrainage in twin-to-twin transfusion syndrome.

OBJECTIVE: To estimate changes in umbilical blood flow (UBF) and Doppler indices in pregnancies complicated by twin-to-twin transfusion syndrome (TTS) treated with either laser therapy or amniodrainage, and to evaluate the influence of the presence of hemodynamic deterioration prior to therapy, as determined by the Quintero stages of severity. METHODS: Forty-eight cases of TTS were included, and further classified into severity Stages I or II (absence of critically abnormal Dopplers (CAD), n = 22) and Stages III or IV (presence of CAD or hydrops fetalis, n = 26). In Stages I-II, 14 cases were treated with laser and eight with amniodrainage, and in Stages III-IV, 17 were treated with laser and nine with amniodrainage. Differences in the UBF, umbilical artery pulstility index (UA-PI) and ductus venosus pulsatility index (DV-PI) were estimated for both groups of severity before and after both treatments. Eleven normal monochorionic pregnancies were evaluated as controls. RESULTS: In recipients, UBF was significantly higher with respect to controls regardless of the stage, while donors had a significant decrease in UBF, but only in Stages III-IV. After laser treatment no changes were observed in fetuses in Stages I-II. In Stages III-IV, recipients showed a significant reduction in the DV-PI (mean DV-PI 1.31 +/- 0.18 vs. 1.05 +/- 0.22; P = 0.005) whereas donors showed a significant increase in the UBF (mean UBF 134 +/- 36 mL/min vs. 195 +/- 25 mL/min; P < 0.001) and in the DV-PI (mean DV-PI 0.99 +/- 0.26 vs. 1.36 +/- 0.42; P = 0.002), and a reduction in the UA-PI (mean UA-PI 1.86 +/- 0.41 vs. 1.58 +/- 0.30; P = 0.01). After amniodrainage only donor fetuses in Stages III-IV showed an increase in UA-PI (mean UA-PI 1.54 +/- 0.35 vs. 1.72 +/- 0.40; P = 0.015). No other changes were observed in any of the parameters studied. CONCLUSION: Laser therapy induces consistent hemodynamic variations in TTS mainly manifested in Stages III-IV.

Amniocentesis↗

The dimerization domain upstream binding factor contains multiple helical structures.

The upstream binding factor, UBF, is an RNA polymerase I transcription factor which contains multiple DNA binding domains and a novel protein dimerization domain. Active UBF forms homodimers in vivo through the intramolecular interactions of its dimerization domain, which spans a hundred amino-terminal residues. In the presence of both UBF dimerization domain and its immediately adjacent lysine-rich basic DNA binding domain, the E. coli expressed recombinant polypeptide, dbUBF (dimerization plus basic motifs of UBF), forms homodimers in vitro and binds to double-stranded DNA nonselectively. In gel retardation assay, dbUBF dimers make multiple shift-ladders corresponding to numerous protein dimer-DNA complexes. The UBF dimerization domain contains multiple helical structures, as predicted by EMBO-PHD program. Most of hydrophobic residues in the dimerization domain are confined in the hydrophobic phase of these hypothetic helices. Mutating these hydrophobic residues to glutamate prohibits dbUBF association and gives a different shift pattern in gel retardation assay. The results we present here argue that UBF association is largely exerted by the hydrophobic interactions between the multiple helices to bring two molecules together.

Amino Acid Sequence↗

Effects of hyperthermia on uterine blood flow and shunting through uterine arteriovenous anastomoses in the late-pregnant ewe.

The effect of maternal hyperthermia on uterine blood flow (UBF) through the two main uterine arteries and on the proportion of UBF shunted through uterine arteriovenous anastomoses (AVAs) was investigated. Eight late-pregnant ewes were exposed to normothermic (22-23 degrees C) or hyperthermic (approximately 39 degrees C) ambient conditions for 8 h. UBF was measured in the left and right uterine arteries using flow probes and microspheres were injected into the uterine artery before, during and after the experimental period. The distribution of microspheres between the uterus and lungs was determined to calculate changes in capillary and AVA blood flows. Hyperthermia produced a significant (P<0.05) increase in maternal core temperature (+1.5 degrees C), increase in maternal blood pH (+0.21; P<0.05) and decrease in maternal pCO2 (-16.2 mmHg; P<0.05). Blood flow to the uterine horn ipsilateral to the corpus luteum (CL) remained unchanged during hyperthermia, whereas total UBF and blood flow to the contralateral uterine horn were significantly decreased (P<0.05), by 23.1% and 20.8%, respectively, of pre-heat control values. The proportion of UBF shunted through uterine AVAs during hyperthermia was not significantly different from values observed in normothermic ewes (21.9 +/- 0.7%). Mild to moderate hyperthermia in late-pregnant sheep induces respiratory alkalosis and decreases total blood flow to the uterus, brought about by a decrease in blood flow to the uterine horn contralateral, but not ipsilateral to the CL. Heat treatment does not alter the proportion of UBF traversing uterine AVAs.

Animals↗

Regulation of rDNA transcription factors during cardiomyocyte hypertrophy induced by adrenergic agents.

Ribosomal DNA transcription is important to the regulation of cardiomyocyte ribosome content and, as a consequence, the rate of protein synthesis and accumulation during cardiac hypertrophy. We studied the regulation of ribosomal RNA synthesis and the levels of RNA polymerase I and the ribosomal DNA transcription factor, UBF, during norepinephrine-induced hypertrophy of contraction-arrested neonatal cardiomyocytes in culture. Nuclear run-on assays and Western blots demonstrated that, concomitant with hypertrophy, norepinephrine (1 microM) increased the rate of ribosomal DNA transcription, without causing an increase in the amount of RNA polymerase I. However, the elevated rate of rRNA synthesis was accompanied by an increased cellular content of UBF protein as determined by Western analysis. Northern blots demonstrated norepinephrine-induced increases in UBF mRNA in neonatal cardiomyocytes indicating that the response was regulated, at least in part, at the pretranslational stage. Both alpha- and beta-adrenergic agents increased the level of UBF mRNA. The beta-adrenergic response was mimicked by forskolin (1 microM) and the cyclic AMP analog dibutyryl cAMP (10 microM). However, activation of protein kinase C by phorbol 12-myristate 13-acetate (0.1 microM) did not increase expression of UBF. These results implicate UBF as a possible regulatory factor of the accelerated rDNA transcription observed during norepinephrine-mediated cardiomyocyte hypertrophy.

Adrenergic Agents↗

Analysis of the phosphorylation, DNA-binding and dimerization properties of the RNA polymerase I transcription factors UBF1 and UBF2.

The phosphorylation, DNA-binding and dimerization properties of both forms of the RNA polymerase I transcription factor UBF were studied and compared. Tryptic peptide maps of in vivo 32P-labeled UBF contained four phospho-peptides. Two of these peptides are predicted to derive from the serine-rich, carboxyl-terminal of UBF. This region contains nine consensus phosphorylation sites for casein kinase II, and is one of the regions phosphorylated in vitro by casein kinase II. Analysis of the DNA-binding properties of recombinant forms of UBF1 and UBF2 by Southwestern blots revealed: (1) a role for the NH2-terminal 102 amino acid domain of UBF1/UBF2 in DNA-binding; (2) the importance of the bases from -106 to -101 of the rat ribosomal DNA promoter for the binding of UBF; and (3) functional differences between UBF1 and UBF2. Glutaraldehyde cross-linking and overlay assays using recombinant forms of UBF1 and UBF2 demonstrated that the molecules can form both homodimers and heterodimers. These assays also demonstrated that the NH2-terminal 102 amino acids of UBF plays a significant role in dimerization and that other domains contribute to dimerization. The dimerization properties of recombinant forms of UBF1 and UBF2 were different, suggesting that the HMG box 2 of UBF1, which is partially deleted in UBF2, also contributes to UBF dimerization.

Animals↗

Cellular regulation of ribosomal DNA transcription:both rat and Xenopus UBF1 stimulate rDNA transcription in 3T3 fibroblasts.

A novel RNA polymerase I (RPI) driven reporter gene has been used to investigate the in vivo role of the architectural ribosomal transcription factor UBF in gene activation and species specificity. It is shown that the level of UBF overexpression in NIH3T3 cells leads to a proportionate increase in the activities of both reporter and endogenous ribosomal genes. Further, co-expression of UBF antisense RNA suppresses reporter gene expression. Thus, UBF is limiting for ribosomal transcription in vivo and represents a potential endogenous ribosomal gene regulator. In contrast to some in vitro studies, in vivo, the mammalian and Xenopus forms of UBF1 show an equal ability to activate a mouse RPI promoter. This activity is severely impaired in mutants compromised for either dimerization or DNA binding. Similarly, the natural UBF2 splice variant shows a severely impaired capacity to activate RPI transcription. The data strongly suggest that UBF predominantly regulates ribosomal transcription by binding to and activating the ribosomal genes, but does not eliminate a possible secondary role in titrating ribosomal gene repressors such as Rb. Consistent with the DNA folding ability and cellular abundance of the UBF, we suggest that the protein may regulate a structural transition between the potentially active and active chromatin states.

3T3 Cells↗

Ulnar-basilic fistula: indications, surgical aspects, puncture technique, and results.

Ulnar-basilic fistula (UBF) is an autogenic vascular access option for hemodialysis (HD) first reported in 1967. However, only a few reports dealing with its complications and survival rates have been published in the literature. In the present work the results of 61 UBFs done in 60 adult patients on chronic HD are reported. Forty UBFs were created as primary access and the remaining 21 UBF as secondary access after: (a) thrombosis of an ipsilateral radiocephalic fistula (RCF) in 6 cases, (b) thrombosis of a contralateral RCF in 7 cases, and (c) thrombosis of a brachiocephalic fistula in 2 cases. No episodes of surgical complications, arterial steal, or ulnar nerve damage were observed. Five UBFs thrombosed within the first week after surgery. The 1-, 3-, and 5-year unassisted survival rates were 70.9%, 67.7%, and 57.3%, respectively, which were significantly higher than those reported previously. The inclusion of UBF in routine access plans is recommended.

Adolescent↗

Mechanism of repression of RNA polymerase I transcription by the retinoblastoma protein.

The retinoblastoma susceptibility gene product pRb restricts cellular proliferation by affecting gene expression by all three classes of nuclear RNA polymerases. To elucidate the molecular mechanisms underlying pRb-mediated repression of ribosomal DNA (rDNA) transcription by RNA polymerase I, we have analyzed the effect of pRb in a reconstituted transcription system. We demonstrate that pRb, but not the related protein p107, acts as a transcriptional repressor by interfering with the assembly of transcription initiation complexes. The HMG box-containing transcription factor UBF is the main target for pRb-induced transcriptional repression. UBF and pRb form in vitro complexes involving the C-terminal part of pRb and HMG boxes 1 and 2 of UBF. We show that the interactions between UBF and TIF-IB and between UBF and RNA polymerase I, respectively, are not perturbed by pRb. However, the DNA binding activity of UBF to both synthetic cruciform DNA and the rDNA promoter is severely impaired in the presence of pRb. These studies reveal another mechanism by which pRb suppresses cell proliferation, namely, by direct inhibition of cellular rRNA synthesis.

Animals↗

Uterine blood flow and timing of blastocyst implantation in the guinea pig.

The temporal and direct relationships between serum estradiol (E) and progesterone (P) levels and uterine blood flow (UBF) and intrauterine oxygen tension (IU PO2) were examined in guinea pigs between days 1 and 8 of pregnancy. Both UBF and IU PO2 were measured in situ using a noninvasive electromagnetic blood flow monitor and needle oxygen electrode, respectively. Serum P levels remained relatively constant throughout the first 8 days of pregnancy. In contrast, serum E levels declined to basal levels between days 1 and 3, and then subsequently rose between days 4 and 7 before again falling to basal levels by day 8. The changes in UBF and IU PO2 paralleled those of serum E levels, both exhibiting a rise between days 5 and 6. The direct effect of oil, E, or P injections on UBF and IU PO2 measurements in ovariectomized animals indicated that E induced a dramatic rise in both uterine parameters, whereas both measurements remained at basal levels after oil or P treatment. The results of this study indicate that UBF and IU PO2 levels are directly regulated by the cyclic fluctuations in serum E. The temporal relationship between the days 4 to 7 rise in serum E, UBF, and IU PO2 levels and the timing of blastocyst implantation suggest that these events are involved in uterine preparation for nidation in the guinea pig.

Animals↗

Role of angiotensin II and prostaglandins in the regulation of uteroplacental blood flow.

This study was designed to determine the importance of the renin-angiotensin (RAS) and prostaglandin (PG) systems in regulating uteroplacental blood flow (UBF). Our objectives were to determine: 1) whether angiotensin II (ANG II) acts as a vasodilator or purely as a vasoconstrictor in the uteroplacental circulation, and 2) whether this circulation is capable of autoregulation. In chronically instrumented pregnant dogs (41-54 days gestation), ANG II was infused intravenously at increasing doses (8, 16, and 24 ng.kg-1 x min-1). Arterial pressure rose from 108 +/- 6 to 146 +/- 4 mmHg and UBF did not change but uterine vascular resistance (UVR) progressively increased. When the experiment was repeated while servo-controlling uterine arterial pressure, UBF fell at all doses, reaching 62 +/- 7% of control at the highest dose, and UVR increased as before. Meclofenamate (6 mg/kg i.v.) did not alter the dose-response curves. In separate experiments, uterine perfusion pressure was reduced in steps to 55 mmHg. UBF was well autoregulated down to approximately 85 mmHg, and neither captopril (14 micrograms.kg-1 x min-1) nor meclofenamate altered UBF autoregulation. Thus ANG II appears to act as a vasoconstrictor in the uteroplacental circulation and any preservation of UBF during ANG II appears to be due to the increased arterial pressure. Also, in the dog the uteroplacental circulation possesses a mild to moderate degree of autoregulatory capability, which does not appear to be dependent on the RAS or PGs.

Angiotensin II↗

H2 gas clearance technique for separating rat uterine blood flow into endometrial and myometrial components.

The H2 gas clearance technique was employed to measure uterine blood flow (UBF) in ovariectomized rats. A needle-type platinum electrode (125 microns diam) was inserted into the rat uterine wall to measure the tissue blood flow surrounding the electrode. The electrode can be placed in individual layers of the uterus to measure the endometrial blood flow (EBF) or the myometrial blood flow (MBF). By use of this technique, baseline EBF and MBF were 37.8 +/- 3.53 (n = 21) and 47.2 +/- 4.56 (n = 5) ml.min-1.100 g-1, respectively, with an EBF/MBF ratio of 0.8. Intravenous bolus injection of 17 beta-estradiol (1 microgram/kg) induced a significant increase in UBF. Phenylephrine, an alpha-adrenergic receptor agonist, reduced UBF. In some animals, a second platinum electrode was used to measure gastric mucosal blood flow simultaneously with UBF. While 17 beta-estradiol selectively increased UBF, pentagastrin selectively increased gastric mucosal blood flow. To further validate the baseline UBF distribution between endometrial and myometrial layers, iodo[14C]antipyrine autoradiography was employed. With the iodo[14C]antipyrine technique, the EBF/MBF ratio was 0.91 +/- 0.07 (n = 5), which is similar to that obtained with the H2 gas clearance technique.

Animals↗

Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep.

Pregnancy is associated with a significant increase in uteroplacental blood flow (UBF), which is responsible for delivering adequate nutrients and oxygen for fetal and placental growth. The present study was designed to determine the effects of vascular insufficiency on fetal and placental growth. Thirty-nine late-term pregnant ewes were instrumented to investigate the effects of chronic UBF reduction. Animals were split into three groups based on uterine blood flow, and all animals were killed on gestational day 138. UBF, which began at 851 +/- 74 ml/min (n = 39), increased in controls (C) to 1,409 +/- 98 ml/min (day 138 of gestation) and in the moderately restricted (R(M)) group to 986 +/- 69 ml/min. In the severely restricted (R(S)) group, UBF was only 779 +/- 79 ml/min on gestational day 138. This reduction in UBF significantly affected fetal body weight with R(M) fetuses weighing 3,685 +/- 178 g and R(S) fetuses weighing 2,920 +/- 164 g compared with C fetal weights of 4,318 +/- 208 g. Fetal brain weight was not affected, whereas ponderal index was significantly reduced in R(M) (2.94 +/- 0.09) and R(S) fetuses (2.49 +/- 0.08) compared with the value of the C fetuses (3.31 +/- 0.08). Placental weight was also significantly reduced in the R(M) group, being 302 +/- 24 g, whereas the R(S) group placenta weighed 274 +/- 61 g compared with the C values of 414 +/- 57 g. Fetal heart, liver, lung, and thymus were all significantly smaller in the R(S) group. Thus the present study shows a clear relationship between the level of UBF and both fetal and placental size. Furthermore, the observation that fetal brain weight was not affected, whereas fetal body weight was significantly reduced suggests that this experimental preparation may provide a useful model in which to study asymmetric fetal growth restriction.

Animals↗

Mechanisms regulating angiotensin II responsiveness by the uteroplacental circulation.

Pregnancy is associated with increases in cardiac output and uterine blood flow (UBF) and a fall in systemic vascular resistance. In ovine pregnancy, UBF rises from approximately 3% of cardiac output to approximately 25% at term gestation, reflecting a >30-fold rise in UBF by term. This increase in UBF supports exponential fetal growth during the last trimester and maintains fetal well-being by providing excess oxygen and nutrient delivery. These hemodynamic changes are associated with numerous hormonal changes, including increases in placental steroid hormones and enhanced activation of the renin-angiotensin and sympathetic nervous systems, all of which are believed to modulate systemic and uterine vascular adaptation and vascular reactivity. Systemic pressor responses to infused ANG II are attenuated in normotensive pregnancies and the uteroplacental vasculature is even less sensitive, suggesting development of mechanisms to maintain basal UBF and permit the rise in UBF necessary for fetal growth and well-being. The effects of ANG II on the uteroplacental vasculature are reviewed, and the mechanisms that may account for attenuated vascular sensitivity are examined, including ANG II metabolism, vascular production of antagonists, ANG II-receptor subtype expression, and the role of indirect mechanisms.

Angiotensin II↗

Regional variations in uterine blood flow in the guinea pig: relationship to pregnancy site distribution.

The alterations which occur in the total uterine blood flow (UBF) during early pregnancy in the guinea pig were determined using electromagnetic blood flow probes. Between days 4 and 6 postcoitum, UBF rose from basal levels of 1.2 ml/min to peak levels of 3.0 ml/min. The elevated levels corresponded temporally with the onset of blastocyst implantation. Between days 7 and 8, UBF declined to basal levels. In guinea pigs possessing three pregnancy sites per uterine horn on days 10-20, obvious regional differences in UBF were observed. Consistently higher UBF measurements were monitored from uterine segmental arteries supplying the tubal and cervical thirds of the uterus than from those distributed to the middle third of the uterus. These data indicate that regional variations in UBF exist in the guinea pig which may be involved in the regulation of pregnancy site selection or subsequent placental-fetal growth.

Animals↗

Relationship between deciduoma formation and uterine blood flow in the pseudopregnant rat.

The relationships between experimentally induced deciduoma formation, circulating estradiol (E) and progesterone (P) levels and alterations in uterine blood flow (UBF) were studied between days 4 and 15 of pseudopregnancy (PSP: day 0 = ovulation) in rats. Blood flow was measured with an electromagnetic blood flow monitor and serum analyzed for E and P levels by radioimmunoassay. Neither uterine trauma on day 4 of PSP nor the site of trauma had any direct influence on altering UBF. A dramatic increase in UBF occurred in response to stromal proliferation on days 5-6 and continued to remain above sham-operated control levels through day 9. These vascular changes correlated temporally with the day 9 peak in uterine weight resulting from deciduoma formation. Both uterine weight and vascular fluctuations in deciduoma-bearing rats were related to the cyclic changes in E/P ratios between days 5 and 8 of PSP. A decline in UBF preceded deciduoma regression between days 9 and 15 of PSP. These results suggest that an increase in UBF is causally associated with the formation and maintenance of deciduoma in the PSP rat and that deciduoma regression may result from a subsequent decline in UBF rates. Both factors may be directly dependent on fluctuating E/P ratios.

Animals↗

Uterine blood flow, pH, and pCO2 during nidation in the guinea pig: ovarian regulation.

The regulation of uterine blood flow (UBF), intrauterine pH (IUpH), and carbon dioxide levels (IUpCO2) by ovarian steroids during the nidatory period was examined in the guinea pig to determine if changes in the intrauterine environment are associated with cyclic changes in ovarian function. Between days 4 and 8 (day 0 = ovulation) of pregnancy, guinea pigs were prepared for the simultaneous in situ measurement of UBF, IUpH, and IUpCO2, and the changes in these parameters were compared to serum levels of 17 beta-estradiol (E2) and progesterone (P). The same parameters were evaluated in ovariectomized guinea pigs treated with oil, 1 or 10 micrograms E2, 2 mg P, or 1 microgram E2 plus 2 mg P (P2E1). UBF rose between days 4 and 5 to peak at the expected time of nidation on day 6 before declining to basal levels by day 8. Similar fluctuations were observed in IUpCO2 and serum E2 levels, while IUpH fluctuated in a manner opposite to that of IUpCO2 levels. Serum P levels remained constant between days 4 and 8. Both P and E2 treatments elevated IUpH but depressed IUpCo2, compared with levels in ovariectomized oil-treated controls. An elevation in UBF rates was also observed in E2-treated animals. Combined P2E1 treatment elevated UBF and IUpCO2 above oil-treated control levels and lowered IUpH. These data indicate that a causal relationship exists among UBF, IUpCO2, and serum E2 fluctuations during the nidatory period in the guinea pig and that these parameters are inversely related to changes in IUpH. It is suggested that ovarian regulation of the intrauterine environment may have a direct effect on the timing of blastocyst implantation in the guinea pig.

Animals↗