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Preeclampsia: evidence for impaired shear stress-mediated nitric oxide release in uterine circulation.

OBJECTIVE: We sought to compare flow-mediated dilatation and myogenic and norepinephrine-induced tone in myometrial resistance arteries from women with preeclampsia and healthy pregnant women and to evaluate the role that nitric oxide may play in these responses. STUDY DESIGN: Arteries (approximately 200 microm, at 50 mm Hg) were dissected from myometrial biopsy specimens from women undergoing emergency cesarean delivery because of preeclampsia (n = 6) and from healthy control subjects undergoing planned cesarean delivery (n = 9). Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine, 10(-6) mol/L) were studied in the absence and presence of the nitric oxide synthase inhibitor N omeganitro-L -arginine (10(-4) mol/L). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium and in the presence of papaverine (10(-4) mol/L). RESULTS: An increase in intraluminal flow led to dilatation of isolated myometrial arteries from healthy gravid women, whereas flow-mediated dilatation was absent in arteries from gravid patients with preeclampsia (increase in diameter at maximum flow rate of 204 microL/min, 28% +/- 5% in healthy gravid patients vs -15% +/- 6% in gravid women with preeclampsia; analysis of variance, P <.05). Addition of N omega-nitro-L -arginine had no significant effect on flow-mediated responses in arteries from women with preeclampsia, whereas flow-mediated dilatation was abolished after addition of N omega-nitro-L -arginine in arteries from healthy gravid women (increase in diameter at a maximum flow rate of 204 microL/min, 28% +/- 5% control vs -9% +/- 5% N omega-nitro-L -arginine; analysis of variance, P <.05). Arteries from women with preeclampsia developed pressure-induced myogenic and norepinephrine-induced tone, similar to that obtained in arteries from healthy gravid women. In arteries from gravid women with preeclampsia, inhibition of nitric oxide synthase enhanced myogenic-induced tone (25% +/- 4% control vs 35% +/- 5% N omega-nitro-L -arginine; P <.05) and norepinephrine-induced tone (36% +/- 4% control vs 46% +/- 6% N omega-nitro-L -arginine; P <.05), as in arteries from healthy gravid women. CONCLUSIONS: Nitric oxide may participate in modulation of pressure- and norepinephrine-induced tone even in preeclampsia, but the shear stress-mediated release of nitric oxide is absent. Failure of shear stress-mediated dilation in myometrial arteries from gravid women with preeclampsia might contribute to the impaired uteroplacental blood flow in this disease.

Adult↗

[Vitamin B1 content of liver, brain and muscles of pregnant and nonpregnant rats with different vitamin B1 supplies].

The purpose of this publication was to examine the effects of a wide variation of dietary vitamin B1 supply (0-12,000 mg vitamin B1 per kg diet) to gravid and non gravid rats on their vitamin B1 content in liver, brain and muscle. The experiment was designed with 176 (2 x 11 x 8) female Sprague-Dawley-rats. Additionally, the organs and tissues were tested as criteria for requirement recommendations. The animals were sacrificed on the 20th day of gravidity of the pregnant rats. Before gravidity the vitamin-B1-contents were 4.7 micrograms/g liver, 2.5 micrograms/g brain and 1.5 micrograms/g muscle. At the end of the experiment the gravid rats had a 19 per cent higher liver content than the non gravids. With a dietary supply of 8-10 ppm vitamin B1 the liver content plateaued until about 120 ppm. Vitamin B1 concentration in brain was about 2 micrograms/g and gravidity was of no effect. Vitamin B1 concentration in muscle was significantly influenced by both factors and saturation was reached at 1.3 and 1.7 micrograms/g muscle. These data showed that the response of the liver to dietary supply was the most sensitive and should therefore be considered in requirements. The requirement for non gravid animals is therefore 4 mg vitamin B1 per kg diet at minimum, gravid animals should be supplied by 7 mg per kg diet.

Animals↗

[Evaluation of variability of duration of pregnancy in mares].

In a set of mares of English Thoroughbred horse of the Napajedla stock the gravidity length in the time period from 1880 to 1972 was evaluated. The variability of the gravidity length was evaluated in sets which were put together by combination of two age groups with a division of the studied time period into ten-year stages. Variance and sample means of the gravidity lengths in these sub-groups are significantly different in the period under study. In order to eliminate the action of non-genetic influences qualifying the variability of the gravidity length, and to increase the objectivity of their evaluation it is proposed not to calculate with absolute values of the gravidity length, but on the contrary with transformed values: (xi - x) divided by s which would be computed for corresponding year of the foaling period. Another methodical approach to exclude the variability of the gravidity length depending on seasonal influences was based on the use of correction factors which were determined for individual months of foaling, on the basis of the sinusoid form of the curve of the gravidity length in the course of the calendar year. When observing the influence of the age of sires on the gravidity length, the shortening of the gravidity length in dependence on their higher age has been suggested, however this relation was significant only sporadically. The submitted work is a part of a larger theme referring, to the reproduction of horses.

Age Factors↗

Inositol phosphate formation in uterine tissue from two species of reptiles is stimulated by arginine vasotocin and influenced by stage of reproduction.

Phosphoinositide hydrolysis, resulting in inositol trisphosphate (IP3) and diacylglycerol (DG) formation, has been implicated in oxytocin-stimulated pulsatile secretion of prostaglandin F2 alpha (PGF2 alpha) from uterine endometrium of sheep and other mammals. In reptiles, arginine vasotocin (AVT) stimulates uterine secretion of PGF2 alpha. These studies investigated the ability of AVT to stimulate incorporation of [3H]inositol into inositol mono-, bis-, and trisphosphates in two reptilian species. In Experiment 1, AVT stimulated (P less than 0.01) IP formation in uterine from late-gravid (150 to 291%) and postpartum (104 to 363%) Yarrow's spiny lizards (Sceloporus jarrovi). Inositol phosphate formation, in response to AVT, was greater (P less than 0.01 for IP3 and P less than 0.05 for total IP) for gravid (stage 40 embryos) and postpartum (1-2 days) lizards near the time of parturition than for lizards at other stages (stage 38-39 embryos or 7 days postpartum). Inositol phosphate formation was greater (P less than 0.05) in uterine tissue from gravid than from postpartum lizards. In Experiment 2, basal IP formation and the response to AVT were the greatest (P less than 0.01) in endometrium from late-gravid American alligators (Alligator mississippiensis). AVT stimulated (P less than 0.02) IP synthesis in uterine endometrium from vitellogenic (136 to 394%), early-gravid (7 to 270%), late-gravid (315 to 1002%), postpartum (86 to 313%), and nonreproductive (292 to 322%) alligators. Results indicate that (1) AVT stimulates IP formation in the uterus of reptiles; (2) uterine IP formation increases in late-gravid reptiles; and (3) increased responsiveness to AVT may occur at parturition or oviposition.

Animals↗

Ecdysteroid concentrations through various life-stages of the meiobenthic harpacticoid copepod, Amphiascus tenuiremis and the benthic estuarine amphipod, Leptocheirus plumulosus.

Endocrine function in arthropods has principally been characterized in insects and malacostracan crustaceans. However, meiofauna represent the most abundant metazoan marine taxa, with harpacticoid copepods comprising the second most abundant taxon. In addition, their diminutive biomass has made characterization of endocrine components difficult, so little is known about endocrine control of reproduction, molting, and growth in meiofauna. In this study, a sensitive fluorometric enzyme immunoassay (EIA) was utilized to quantify and compare the arthropod molting hormone, 20-hydroxyecdysone (20E), in various life-cycle and developmental stages of a laboratory reared meiobenthic copepod, Amphiascus tenuiremis, and in an amphipod, Leptocheirus plumulosus. In copepods, gravid females carrying late stage pre-hatch embryos contained significantly more 20E (390+/-252 fmol/female) than gravids carrying early (Stage-I) embryos (172+/-83 fmol/female). In contrast, ecdysteroid levels in Stage-I L. plumulosus gravid females (277+/-83 fmol/female) was greater than pre-hatch gravid females (146+/-42). Stage-I embryos of both copepods (19+/-10) and amphipods (11+/-5 fmol/embryo) possessed lower ecdysteroid content than copepod (35+/-15) and amphipod (43+/-33 fmol/embryo) pre-hatch embryos. Ecdysteroid levels were also assessed in naupliar, juvenile, adult male and non-gravid female copepod life-stages. In addition, ecdysteroids measured in field collected copepod species indicated gravid females possessed ecdysteroid levels similar to gravid A. tenuiremis. However, upon normalization of egg sac 20E content by brood size, embryos from larger broods contained lower levels of ecdysteroids when compared to embryos from smaller clutch sizes-indicating an inverse embryo/ecdysteroid relationship may exist across species.

Aging↗

[Concentrations of thyroxine, beta carotene, vitamin A and pregnancy in heifers after administration of beta carotene].

Serum concentrations of thyroxine (T4), beta-carotene (beta K), vitamin A and conception after the first insemination on the zero, sixth and 21st day were studied in 63 heifers fed synthetic beta K supplement in groups I to IV at stanchion housing and low-carotene diet. The following amount of beta K was supplemented per head/day: I--0 mg (control, n = 17), II--100 mg (n = 16), III--200 mg (n = 14) and IV--400 mg (n = 16). The parameters were evaluated separately according to groups and conception. By comparing the T4 concentration between experimental groups and control, separately in non-gravid and gravid animals, a significant increase (P less than 0.05) was determined only on the zero day in the fourth group. At the same time, in the fourth group, in comparison with the others, insignificantly lower T4 values were recorded in non-gravid animals. beta K values on the zero day in gravid animals increased in a direct proportion to the higher supplement (P less than 0.05; P less than 0.01; P less than 0.001); in non-gravid animals the increase was slower (P less than 0.05; P less than 0.05; P less than 0.01), but differences in relation to gravidity were not significant. An increase of beta K had no significant effect on serum concentrations of vitamin A. Differences between groups as far as conception was concerned were insignificant. It follows from the results that increasing rates of beta K, with the exception of serum concentrations, had no significant effect on other parameters. Higher concentrations of T4 and a slower increase of beta K in non-gravid animals, however, point at mutual co-operation relation and its positive effect on conception in animals.

Animals↗

[Pregnancy and diabetes].

There is a mutual effect between gravidity and diabetes. Diabetes can have disadvantageous effect over gravidity, but the state of gravidity can contribute to the earlier diagnosis of diabetes. The author had 4850 cases of gravidity of 1686 women, indiscriminately, suffering from diabetes observed and on the basis of his observation he found that the manifestations of diabetes in the state of gravidity are respectively infrequent nowadays but the number of manifestation increases parallel with the fatness of women. The transitional diabetogen effect, the pathologic gravidities and the huge-embryos are, however, able to indicate the early stage of diabetes, that other methods or medical examinations could not still indicate. The birth of huge-embryos is the earliest and most characteristic praediabetic sign and it can appear 30 to 50 years before the development of diabetic trouble of metabolism. The number of pathological gravidities increases parallel with the advance of diabetic manifestation. The author emphasises on basis of his observations the importance of obstetrical and pregnancy-anamnesis in the prevention of diabetic manifestation and in the reduction of foetal losses.

Adult↗

The effect of pregnancy and contractile activity on bladder muscarinic receptor subtypes.

In the rabbit bladder, pregnancy and prolonged bladder contractions decrease both muscarinic receptor density and contractile response, whereas newborns show enhanced muscarinic contractile response. Although the M(2) receptor predominates in rabbit bladder, we and others have shown that the affinity of a series of subtype selective muscarinic antagonists for inhibition of muscarinic agonist-induced contractions is most consistent with the pharmacologically defined M(3) receptor directly mediating smooth muscle contraction. Bladders from fetal rabbits, gravid rabbits, and male rabbits exposed to 4 hr of induced spontaneous contractions were used to determine whether changes in receptor density and contractility are due to a selective decrease in either the M(2) or M(3) muscarinic receptor subtype. To determine organ specificity, the heart and uterus were also studied. Gravid rabbits of 3 weeks' gestation and their fetal rabbits were studied. In male rabbits, bladder contractions were induced for 4 hr by ligating the catheterized penis at its base. Muscarinic receptor density and subtype distribution were determined by radioligand binding and immunoprecipitation. Receptor density was 24% lower in gravid bladder body, unchanged in gravid bladder base, 54% lower in gravid uterus, 115% higher in fetal bladders, and 34% lower after induced bladder contractions. Immunoprecipitation showed greater M(2) receptors than M(3) in all tissues studied, whereas M(l) and M(4) receptors were undetectable. There was no difference from control in the ratio of M(2) to M(3) receptor in any tissues except that a greater proportion of M(3) receptors was found in male vs. female bladders. Changes in contractile response to cholinergic stimulation in the gravid, fetal, and experimental detrusor instability model are associated with changes in total receptor density and not solely with changes in the M(3) receptor subtype that mediates bladder smooth muscle contraction. Neurourol. Urodynam. 18:511-520, 1999.

Animals↗

Reproductive alterations in adult grass shrimp, Palaemonetes pugio, following sublethal, chronic endosulfan exposure.

Grass shrimp (Palaemonetes pugio) populations exposed to anthropogenic contaminant sources in South Carolina (SC) have reduced densities when compared with populations at SC-reference sites. This laboratory study examined the effects of a commonly used agricultural insecticide, endosulfan, on grass shrimp reproduction. Reproductively active grass shrimp were chronically exposed to sublethal concentrations of endosulfan (200 or 400 ng/l) for 43 days. The cumulative number of females that became gravid and the rate at which they became gravid were measured. Endosulfan exposure reduced the cumulative number of gravid females by 31% in the 200 ng/l exposure and 39% in the 400 ng/l exposure. The first appearance of gravid females in the population was significantly delayed in treated populations compared with the control treatment in a dose dependent manner. Clutch size in these gravid females was not significantly different among the treatments. Additionally, there was no difference in the onset of reproduction in the treated populations. These results implicate a population reduction due to a decrease in the overall number of females becoming gravid in a population over time, not a reduction in clutch size per individual. While the mechanisms of action have yet to be defined, these results indicate that sublethal endosulfan concentrations may have a negative effect on grass shrimp reproductive biology.

Animals↗

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae.

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. METHODS: Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. FINDINGS: By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. INTERPRETATION: In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.

Adolescent↗

Electroantennogram and oviposition bioassay responses of Culex quinquefasciatus and Culex tarsalis (Diptera: Culicidae) to chemicals in odors from Bermuda grass infusions.

Odors were collected from the headspace above fermented infusions of Bermuda grass, which commonly are used as attractants in traps for gravid mosquitoes. Coupled gas chromatography-electroantennogram detection (GC-EAD) was used to identify 9 compounds (phenol, p-cresol, 4-ethylphenol, indole, 3-methylindole, nonanal, 2-undecanone, 2-tridecanone, naphthalene) from odor extracts that elicited significant antennal responses from antennae of gravid female Culex quinquefasciatus Say and Culex tarsalis Coquillett mosquitoes. Several of these compounds at appropriate concentrations were weakly attractive to gravid female mosquitoes in laboratory bioassays and/or stimulated more oviposition than water controls. In addition, dimethyltrisulfide, a significant component of odor extract which did not elicit strong responses from female mosquito antennae in GC-EAD assays, also appeared to stimulate oviposition at 1 concentration. A reconstituted blend of the 10 compounds resulted in much stronger and more consistent responses than individual compounds. The blend was attractive to gravid Cx. quinquefasciatus and enhanced oviposition over a range of concentrations spanning 3 orders of magnitude. One concentration of the blend also attracted gravid Cx. tarsalis and enhanced oviposition. However, at the highest concentration tested, the blend was repellent to both species. Overall, these studies demonstrated that gravid mosquitoes are attracted to oviposition sites by blends of compounds rather than by individual chemicals, and that the concentration of compounds in the odor is a critical factor in determining whether responses are positive (attractive, stimulatory) or negative (repellent, deterrent).

Animals↗

Evidence for a local fetal influence on myometrial oxytocin receptors during pregnancy in the tammar wallaby (Macropus eugenii).

Mesotocin (MT), the oxytocin-like peptide of the tammar wallaby (Macropus eugenii) is important for delivery of live young. The tammar mesotocin receptor (MTR) was first characterized using the iodinated oxytocin receptor antagonist [125I]d(CH2)5 [Tyr(Me)2, Tyr4, Orn8, Tyr-NH(2)9]-vasotocin. MTR concentrations were then measured in matched samples of gravid and nongravid myometrium and median vagina at different stages of the 26-day pregnancy. MTR concentrations in both the gravid and nongravid myometrium changed significantly (ANOVA, p < 0.01) during pregnancy. There was no difference in MTR concentrations between uteri on Days 8-22. From Day 23 of pregnancy, MTR concentrations in the gravid myometrium increased (615.8 +/- 144.0 fmol/mg protein), whereas in the nongravid myometrium, they remained unchanged (248.6 +/- 65.5 fmol/mg protein). Receptor concentrations were high in the gravid myometrium during the last 3 days of pregnancy but decreased significantly in the nongravid myometrium. In the median vagina, MTR concentrations were low compared with myometrial tissues and did not increase at term. Changes in MTR concentrations paralleled changes in uterine responsiveness to exogenous MT in vitro. Our data show that MTR concentrations and the responsiveness to MT differ between the gravid and nongravid myometrium during pregnancy. The increase in MTRs in the gravid myometrium and the decrease in the nongravid suggest that different factors influence these receptors in the separate uteri, independent of systemic influence.

Animals↗

The role of oxytocin and regulation of uterine oxytocin receptors in pregnant marsupials.

The oxytocin-like peptide of most Australian marsupials is mesotocin, which differs from oxytocin by a single amino acid. This substitution has no functional significance as both peptides have equivalent affinity for and biological activity on the marsupial oxytocin-like receptor. A role for mesotocin in marsupial parturition has been demonstrated in the tammar wallaby where plasma mesotocin concentrations increase less than one minute before birth. Infusion of an oxytocin receptor antagonist at the end of gestation disrupts normal parturition, probably by preventing mesotocin from stimulating uterine contractions. In the absence of mesotocin receptor activation, a peripartum surge in prostaglandins is delayed which suggests a functional relationship between mesotocin, prostaglandin release and luteolysis. Female marsupials have anatomically separate uteri and in monovular species, such as the tammar wallaby, only one uterus is gravid with a single fetus whereas the contralateral uterus remains non-gravid. We have used this unique animal model to differentiate systemic and fetal-specific factors in the regulation of uterine function during pregnancy. The gravid uterus in the tammar wallaby becomes increasingly sensitive to mesotocin as gestation proceeds, with the maximum contractile response observed at term. This is reflected in a large increase in mesotocin receptor concentrations in the gravid uterus, and a downregulation in the non-gravid uterus in late pregnancy. The upregulation in myometrial mesotocin receptors is pregnancy-specific and independent of systemic steroids. One factor that may influence mesotocin receptor upregulation in the gravid uterus in late pregnancy is mechanical stretch of the uterus caused by the growing fetus. Our data highlight that a local fetal influence is more important than systemic factors in the regulation of mesotocin receptors in the tammar wallaby.

Animals↗

Adenomyosis and risk of preterm delivery.

OBJECTIVE: To evaluate the risk of preterm delivery in patients with adenomyosis. DESIGN: A 1:2 nested case-control study. SETTING: Tertiary-care institution. POPULATION: A base cohort population of 2138 pregnant women who attended routine prenatal check-up between July 1999 and June 2005. METHODS: From this base cohort population, gravid women with singleton pregnancy who delivered prior to the completion of 37 weeks of gestation were identified and formed the study group. Singleton gravid women who had term delivery and who matched with age, body mass index, smoking, and status of previous preterm delivery were recruited concurrently and served as control group. Preterm delivery cases were further divided into spontaneous preterm delivery and preterm premature rupture of membranes (PPROM) cases. MAIN OUTCOME MEASURES: Risk analysis of preterm delivery between gravid women with and without adenomyosis. RESULTS: One-hundred and four preterm delivery case subjects and 208 control subjects were assessed. Overall, gravid women with adenomyosis were associated with significantly increased risk of preterm delivery (adjusted odds ratio 1.96, 95% CI 1.23-4.47, P=0.022). For subgroup analysis, gravid women with adenomyosis had an adjusted 1.84-fold risk of spontaneous preterm delivery (95% CI 1.32-4.31, P=0.012) and an adjusted 1.98-fold risk of PPROM (95% CI 1.39-3.15, P=0.017). CONCLUSIONS: Gravid women with adenomyosis were associated with increased risk of both spontaneous preterm delivery and PPROM. A common pathophysiological pathway may exist in these two disorders. Further in-depth biochemical and molecular studies are necessary to explore this phenomenon.

Case-Control Studies↗

Osmoregulation during pregnancy in the rat. Evidence for resetting of the threshold for vasopressin secretion during gestation.

Osmoregulation was studied in near term and age-matched Sprague-Dawley rats. Basal plasma osmolality (P(osm)) and plasma sodium (P(Na)) were 281+/-3 mosmol/kg and 134+/-3 meq/liter, respectively, on the 20th gestational day compared with 292+/-3 mosmol/kg and 140+/-1 meq/liter in virgin animals (P < 0.001), whereas P(urea) and plasma water content were similar in pregnant and control rats. These differences could not be reproduced in animals receiving progesterone, estrone, or a combination of progesterone and estradiol for 2 wk. Pregnant and control rats were deprived of water for periods ranging from 0 to 48 h. P(osm), always lower in gravidity, was 290+/-3 mosmol/kg after 2 d of water deprivation in pregnant animals compared with 300+/-2 mosmol/kg in controls (P < 0.001). Thus 48 h of dehydration were required before P(osm) in gravid rats was similar to basal values in the age-matched virgins. Despite strikingly lower P(osm), plasma arginine vasopressin (P(AVP)) and urinary osmolality (U(osm)) were similar in the basal state averaging 2.16+/-0.78 pg/ml and 1,652+/-406 mosmol/kg, respectively, during pregnancy compared with 2.08+/-2.17 pg/ml and 1,483+/-203 mosmol/kg in controls (NS). Water deprivation increased P(AVP) and U(osm) similarly in pregnant and virgin rats: these values reached 22.7+/-3.3 pg/ml and 3,300+/-123 mosmol/kg at 48 h in gravid compared with 26.0+/-6.4 pg/ml and 3,342+/-141 mosmol/kg in the controls (NS). Regression equations for P(AVP)vs. P(osm) which were highly significant (P < 0.001) in both groups demonstrated an apparent threshold for AVP secretion approximately 11 mosmol lower in gravid animals. Intravascular volume decreased, and plasma aldosterone increased during water deprivation, and both changes (Delta%) were significantly greater in the gravid animals (P <0.01). Therefore, P(osm) was increased without concomitant volume depletion by intraperitoneal hypertonic saline. Again P(AVP)vs. P(osm) correlated significantly (r > 0.9; P < 0.001) in each group, and the apparent threshold was 14 mosmol lower in pregnant animals. Diluting ability, tested by oral water loading, was not impaired in the pregnant animals which excreted a 30 ml/kg load as well as controls. Also, chronically hydrated virgin animals whose fluid intake was more than twice that of pregnant rats (for 19 d) did not lower their P(osm). In separate studies homozygous Brattleboro rats, which produce no endogenous vasopressin, were also shown to have a decreased P(osm) (pregnant 292+/-4 mosmol/kg; virgin 310+/-6 mosmol/kg P < 0.001), but unchanged U(osm) during pregnancy. Data demonstrate a resetting of the osmostat in gravid Sprague-Dawley rats as P(osm) and the threshold for AVP secretion both decrease significantly during gestation in this species. Studies in homozygous Brattleboro animals with hereditary diabetes insipidus suggest that the osmotic threshold for thirst is reset as well.

Animals↗

Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals.

We investigated the effects of uterine stretch on the levels of messenger RNA (mRNA) encoding the gap junction proteins connexin-43 (Cx-43) and connexin-26 (Cx-26) as well as the presence of gap junction plaques formed by Cx-43 within the myometrium. In nonpregnant ovariectomized rats, stretch of one uterine horn with a polyvinyl tube induced a significant increase in myometrial Cx-43 mRNA levels, an effect that was blocked by progesterone; no expression of Cx-26 was detected in the presence or absence of stretch. To investigate whether pregnancy and parturition modified the response to stretch, unilaterally pregnant rats underwent either sham operation or placement of a tube in the nongravid uterine horns. On day 20 of pregnancy, expression of Cx-43 mRNA in gravid horns was low, and stretch did not increase this level. Cx-26 mRNA expression was elevated at this time, but only in the gravid horns. Cx-43 mRNA was highly expressed in the myometrium of gravid horns during labor, but Cx-43 expression in sham-operated, nongravid horns remained low. In contrast, nongravid horns stretched with tubes expressed Cx-43 mRNA at levels similar to those in gravid horns. Levels of Cx-26 mRNA in gravid horns fell between days 20 and 23, and this was not altered by stretch. Punctate Cx-43 immunofluorescence (indicative of gap junction formation) also increased in the myometrium after uterine stretch and in gravid horns during labor. Our data demonstrate that differential mechanisms regulate the expression of Cx-43 and Cx-26 in the pregnant myometrium. Cx-43 expression during labor is dependent upon myometrial stretch under conditions of low progesterone. In contrast, Cx-26 expression during late pregnancy, although requiring the presence of the fetal/placental unit, does not require stretch of the myometrium.

Animals↗