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PubMed1997

Reflex haemodynamic responses caused by distension of the uterus in anaesthetized pigs.

The present study was undertaken in anaesthetized pigs to determine whether distension of the uterus reflexly affects the aortic blood pressure, heart rate, left ventricular inotropic state and the coronary circulation. Experiments were performed in 17 pigs anaesthetized with alpha-chloralose and artificially ventilated. Coronary blood flow was measured with an electromagnetic flowmeter positioned around the origin of the left circumflex coronary artery. The uterus was distended by injecting 20 ml warm Ringer solution into a balloon positioned within the uterus (mean transmural pressure of about 17 mmHg). Distension of the uterus without controlling any haemodynamic variable caused an increase in aortic blood pressure. When this response was prevented, an increase in heart rate was obtained in each animal. When the heart rate and blood pressure responses were prevented, the distension did not cause significant changes in the maximum rate of change of left ventricular pressure, but always caused a decrease in mean coronary blood flow. In five pigs, the increase in heart rate and the decrease in mean coronary blood flow were graded by step increments of distension. In six pigs, the haemodynamic responses to distension of the uterus were not affected by the administration of atropine. In 12 pigs, which included the six given atropine, the increase in heart rate was abolished by the administration of propranolol and the increase in aortic blood pressure and the decrease in mean coronary blood flow were abolished by the subsequent administration of phentolamine. In the remaining five pigs, the haemodynamic responses caused by uterine distension were abolished by the administration of bretylium tosylate. The present study showed that distension of the uterus in anaesthetized pigs primarily caused reflex increases in heart rate and aortic blood pressure and coronary vasoconstriction. These reflex responses were mediated by efferent sympathetic mechanisms.

Afferent Pathways↗
PubMed2000

Clinical implications of the didelphic uterus: long-term follow-up of 49 cases.

OBJECTIVE: The aim of the study was to evaluate reproductive performance of women with didelphic uterus and to consider possible long-term consequences associated with this uterine anomaly. STUDY DESIGN: Forty-nine women were diagnosed as having a didelphic uterus with a longitudinal vaginal septum at Tampere University Hospital, Finland between 1962 and 1998. The presence of other anomalies, gynecologic disorders, fertility and outcome of pregnancies were reviewed. The long-term clinical implications associated with a didelphic uterus were evaluated during the mean (S.D.) follow-up period of 9.1 (6.3) years. RESULTS: An obstructed hemivagina was found in nine (18%) out of forty-nine cases; eight of these had ipsilateral renal agenesis. A longitudinal vaginal septum was excised in twenty-six (53%) cases, but metroplasty in none. Five (13%) patients had primary infertility. Thirty-four (94%) out of thirty-six women who wanted to conceive had at least one pregnancy, and they produced seventy-one pregnancies; 21% miscarried, and ectopic pregnancy occurred in 2%. The fetal survival rate was 75%, prematurity 24%, fetal growth retardation 11%, perinatal mortality 5. 3%, and cesarean section rate 84%. Pregnancy located more commonly (76%) in the right uterus than in the left. During the follow-up period endometriosis was observed in seven (16%) out of forty-five cases. Ovarian neoplasm was found in four (9%) cases, one of them had ovarian cancer. CONCLUSIONS: Fertility in women with didelphic uterus is not notably impaired. The prognosis of pregnancy is comparatively good, while prematurity and fetal growth retardation indicate meticulous prenatal care. Long-term follow-up did not reveal that didelphic uterus is associated with increased frequency of endometriosis or genital neoplasm.

Adolescent↗
PubMed1978

Intracellular relationships of the oestrogen receptor in the rat uterus and hypothalamus during the oestrous cycle.

Simultaneous measurements were made of the specific oestrogen receptor in the nuclear and cytosol fractions prepared from the uterus and hypothalamus of 50--81-day-old female rats undergoing a 4-day oestrous cycle. In the uterus, the content of nuclear receptor fluctuated in concert with known cyclic changes in the secretion of oestrogen, being maximal at pro-oestrus. Over the period of 50--81 days, the nuclear content at all phases increased with age, again corresponding to known age-related increases in ovarian secretion of oestrogen. This age-related increase in nuclear content, averaged from the values of the different phases in each age group, was related to equivalent increases in uterine wet weight, an increase of 1 pmol of receptor being accompanied by an increase of 80--90 mg. The concentration of cytosol receptor was maintained constant, with respect to wet weight, throughout the cycle and with age, irrespective of changes in nuclear content. In the uterus of normal mature females, translocation of receptor into the nucleus did not lead to depletion of cytosol receptor, suggesting a process of continuous replenishment/synthesis. In the hypothalamus, the nuclear content of oestrogen receptor was also maximal at pro-oestrus. In contrast with the uterus, the content of hypothalamic cytosol receptor was minimal at this phase and reflects depletion of the cytosol receptor, possibly as a result of translocation. The extent of translocation was low compared with that in the uterus and did not alter with age during the age-period studied. This low nuclear binding of the receptor in vivo is discussed in relation to the presence of a cytosol factor, present in limiting amounts, which in vitro mediates the binding of cytosol receptor to oligo(dT)-cellulose. The difference in the physiological response of the uterus and of the hypothalamus to oestrogens may be related to the extent of nuclear binding of receptor.

Animals↗
PubMed1999

The effects of histamine on the isolated mouse uterus.

1. A study is made of the contractile and relaxant effects, and mechanism of action, of histamine on isolated uterus from mice treated with diethylstilboestrol, employing acetylcholine and adrenaline as contractile and relaxant standard agents. 2. Concentration-response curves for histamine agonists were obtained in the absence and presence of selective histaminergic blocking drugs (clemizole, ranitidine and thioperamide) and indomethacin. A number of experiments were carried out in uterus from reserpinised mice. Concentration-response curves for acetylcholine and adrenaline were also obtained in the absence and presence of their selective antagonist (atropine and propranolol). 3. In isolated oestrogenised mouse uterus, histamine and acetylcholine produced a concentration-related contractile response. When the uterus was precontracted with KCl, histamine at lower doses produced a slight contraction, though in the presence of clemizole it induced concentration-related relaxation, reminiscent of that produced by adrenaline. Atropine and propranolol antagonised the contractile and relaxant effects of acetylcholine and adrenaline, respectively. 4. In isolated uterus from reserpinised mice, histamine and 2-pyridylethylamine, but not 4-methylhistamine, produced a concentration-related contractile response. Ranitidine potentiated the contractile effect of histamine, though clemizole--in the presence of ranitidine--competitively antagonised the contractile effect of histamine (pA2 = 10.50 +/- 0.81). The concentration-relaxant curve of histamine in the presence of clemizole was not modified by ranitidine or indomethacin, but shifted to the right with thioperamide. The same displacement was also observed in the presence of clemizole plus ranitidine. 5. In mouse isolated uterus, histamine mainly produced contraction mediated by histamine H1-receptors, though the existence of histamine H2- or H3-receptors mediating relaxation could not be excluded.

Acetylcholine↗
PubMed1995

Accuracy of ultrasonic detection of the uterus in normal newborn infants: implications for infants with ambiguous genitalia.

Every year approximately one in 5000 babies is born with ambiguous genitalia, a condition that requires immediate sex assignment if possible. We investigated whether transabdominal ultrasonography with the use of a linear array high-resolution 7.5-MHz transducer would enhance the accuracy of detecting the uterus in the newborn. One hundred mothers who delivered normal, term infants (> 36 weeks and > 2500 g) gave their informed consent for the investigation. Each infant was placed in an unmarked bassinet, external genitalia were covered, and ultrasound examinations were performed by the same examiner (R.S.) who was blinded to the sex of the infant. The neonatal uterus was identified in 47 of 50 female infants (94% sensitivity) and the absence of a uterus was correctly predicted in 49 of 50 male infants (specificity 98%). The average length of the neonatal uteri 1 day after birth was 3.2 +/- 0.5 cm and the total volume was 3.5 +/- 0.9 cm3. An endometrial strip could be identified in 98% of neonatal uteri. We conclude that the use of the high-resolution 7.5-MHz transducer available in commercial ultrasound equipment is an accurate method for the detection of the neonatal uterus. Infants born with ambiguous genitalia who have a uterus will almost always be assigned the female sex. Infants with ambiguous genitalia but without a uterus will have male pseudohermaphroditism.

Cervix Uteri↗
PubMed1983

Utero-ovarian relationships in placental mammals: role of uterus and embryo in the regulation of progesterone secretion by the corpus luteum. A review.

The role of the uterus and that of the embryo in regulating luteal progesterone secretion appear to differ greatly, depending on the mammal. However, the situation is analogous in some mammals. The main role of luteal progesterone is to permit the establishment and maintenance of pregnancy, and there appears to be a relationship between the type of placenta and the uterine and embryonic modes of regulating luteal activity. When placentation is endotheliochorial (carnivores), the corpus luteum is active over a remarkably long period; the uterus does not have any limiting action in any of the species studied and the presence of an embryo does not profoundly modify luteal progesterone secretion. When placentation is epitheliochorial (artiodactyls), hysterectomy, like the presence of an embryo in the uterus, considerably prolongs luteal activity in all the species studied. The uterus limits the duration of progesterone secretion by producing luteolytic PGF2 alpha. The embryo maintains progesterone secretion by acting directly on the uterus, causing a change in the synthesis of prostaglandins; this change eventually favors the synthesis of luteotropic PGE's. Moreover, the embryo secretes LH-like and possibly prolactin-like luteotropic factors. When placentation is hemochorial (rodents, lagomorphs, higher primates), the uterus plays a slight role or none at all in regulating luteal activity in all the species studied. The presence of an embryo prolongs and often increases progesterone secretion. The embryo acts in two ways: (a) by causing decidual tissue to form in the endometrium; this tissue secretes the luteotropic factors, uterine "prolactin" and sometimes PGE, and (b) by secreting an LH-like chorionic hormone that is produced in large quantities in primates.

Animals↗
PubMed1985

Studies on the energy metabolism of the pregnant sow. 1. Uterus and mammary tissue development.

Twenty-six gilts were used in an experiment to study the effects of level of feed intake on the growth and chemical composition of the gravid uterus and mammary tissue at several stages of gestation. The animals were given either 1.8 or 2.5 kg feed/d (20 or 30 MJ metabolizable energy (ME) respectively) and were slaughtered at intervals between days 40 and 110 of gestation. The gravid uterus was dissected into fetal, placental, fluid and empty uterus components. From day 70 of gestation the mammary tissue was also dissected. The fresh weight and dry matter (DM), energy and nitrogen contents of the various tissues were determined. With the exception of the fluid component, there was a significant increase (P less than 0.01) in the fresh weight of each tissue with both stage of gestation and level of feeding. At comparable litter sizes the total weight of the fetuses in late gestation was 16% higher with the higher feed intake. The DM content of the individual uterine tissues increased significantly (P less than 0.01) with increase in stage of gestation so that the mean DM content of the gravid uterus increased from 74.6 g/kg at day 50 to 103.1 and 159.0 g/kg at days 90 and 110 of gestation respectively. Neither stage of gestation nor feeding level influenced the respective energy contents of the individual uterine tissues, when expressed per g DM. The mean energy content of the total gravid uterus was 19.5 kJ/g DM. The N content (g/g fresh weight) of the tissues increased with stage of gestation and was generally higher at the higher feeding level. The mean N contents (g/g DM) of the fetal, placental, fluid and empty uterine tissues were 0.090, 0.101, 0.098 and 0.128 respectively. The mammary tissue was the most variable of all the tissues investigated. Whereas the fresh weight and N content increased with stage of gestation, both the DM and energy content decreased. Gompertz equations were fitted to describe the effects of stage of gestation, level of feed intake and liter size on the fresh weight and chemical content of the individual uterine tissues, total gravid uterus and mammary tissue. The use of these equations for calculating the nutrient requirements of pregnancy is demonstrated. It was calculated that between days 50 and 110 of gestation the ME requirement for reproduction increased from 3 to 12% of maternal energy intake. The calculated requirement for protein was from 7 to 41% of maternal dietary protein intake respectively.

Animals↗
PubMed1996

Differential regulation of nitric oxide in the rat uterus and cervix during pregnancy and labour.

The aim of this study was to determine if nitric oxide (NO) production and nitric oxide synthase (NOS) isoforms change within the uterus and cervix during pregnancy and labour either at term or preterm. NO production was compared in the rat uterus and cervix of non-pregnant and pregnant rats on days 18-22 prior to labour, day 22 during delivery, 1 day post-partum and after treatment with either 10 mg onapristone or progesterone. Uterine NO synthesis, reflected in nitrite production, increased during gestation (194.2 +/- 22.6 nmol/g on day 19) compared with the non-pregnant state (76.2 +/- 18.4 nmol/g, P < 0.05) and decreased during term labour and post-partum. Furthermore, injection of lipopolysaccharide (LPS) (100 micrograms/rat i.p.) on day 20 of gestation resulted in a significant increase in NO synthesis after 6 h. Conversely, cervical NO synthesis and nitrite production was low in the non-pregnant (65.1 +/- 9.2 nmol/g) and pregnant animals on days 18-22 of gestation (53.2 +/- 9.0 nmol/g on day 22, P > 0.05), but markedly increased during term labour (139 +/- 28.6 nmol/g, P < 0.05). Treatment with the antiprogestin onapristone suppressed uterine NO production and increased cervical production while continuous administration of progesterone from day 19 had the opposite effect. LPS produced a significant increase in cervical NO production in both the pregnant (8-fold) and non-pregnant (4-fold) states. All three known NOS isoforms (i.e., iNOS, nNOS and eNOS) were detected in the cervical samples but only two were present in the uterus (iNOs and eNOS). An increase in the presence of iNOS occurred during labour at term compared with cervices collected from day 19. This was contrary to the measurements of the isoform in the uterus. Also, there was a similar increase of nNOS in the cervix during labour. This isoform seemed absent in the uterus during gestation. No significant changes occurred in the abundance of eNOS in the cervix during labour at term compared with day 19. During preterm labour after onapristone, iNOS concentrations increased significantly in the cervix. In order to examine whether the NO pathway plays a role in cervical ripening, the effects of the nitric oxide synthesis inhibitor L-nitro-arginine methylester (L-NAME) on the duration of delivery and on cervical extensibility were also investigated. The duration of delivery was significantly prolonged in L-NAME-treated rats compared with the control group (2.4-fold). Moreover, cervical extensibility decreased significantly (1.7-fold) after in-vitro incubation with L-NAME (P < 0.005). We conclude that the NO system may have an active role in the cascade of processes involved in preparing the uterus and cervix for parturition.

Animals↗
PubMed2005

Estrogens and glucocorticoids have opposing effects on the amount and latent activity of complement proteins in the rat uterus.

The mammalian uterus faces unique immunological challenges. It must nurture and protect the semiallogenic fetus from attack by the maternal immune system while guarding against infection by pathogens that compromise fetal and maternal health. Complement has recently been implicated in the etiology of pregnancy loss, but its regulation by steroid hormones and its role in host defense in the uterus are not clearly defined. Here we use biochemical, functional, and physiological assays to elucidate the regulation of complement proteins in the rat uterus. We demonstrate that estrogens (17 beta-estradiol) and glucocorticoids (dexamethasone) have major, but opposing, effects on the amount and latent activity of complement effectors in the uterus. Treatment with 17 beta-estradiol induced vasodilation and an increase in vascular permeability, which resulted in extravasation of plasma and complement into the uterus, rather than de novo complement biosynthesis. In vitro assays revealed that 17 beta-estradiol induced a potent bactericidal activity in uterine luminal fluid and that the antibacterial component was complement. These proinflammatory and immunomodulatory effects were evident within 4 h of treatment and were blocked by coadministration of dexamethasone. We also found that estrogen effects on the vasculature were mediated in part by activation of the contact system and bradykinin B1 receptors. These results indicate that complement plays a central role in innate immunity in the female reproductive tract and suggest that estrogens or glucocorticoids might be used therapeutically to enhance or inhibit complement-dependent processes in the uterus.

Animals↗
PubMed1992

Expression of insulin-like growth factor-I (IGF-I) and its receptor in the peri-implantation mouse uterus, and cell-specific regulation of IGF-I gene expression by estradiol and progesterone.

This study describes the expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) genes in the mouse uterus during the peri-implantation period (Days 1-6 of pregnancy), as well as effects of estradiol (E) and progesterone (P) on cell-specific IGF-I gene expression in the uterus of the ovariectomized adult mouse. Northern blot analysis showed that IGF-I mRNA levels were low but readily detectable in the uterus on Day 1 of pregnancy and steadily increased, reaching high levels just before (Day 4) and after initiation of implantation (Days 5 and 6). In general, IGF-IR transcripts were present in low abundance in uterine RNA throughout the peri-implantation period. However, six sizes of uterine IGF-IR transcripts were detected, and the relative abundance of two of these transcripts varied significantly during the peri-implantation period. Cell-specific expression of the IGF-I gene was examined by in situ hybridization to mRNA and immunohistochemical detection of protein. The results indicated that the synthesis of IGF-I on Days 1 and 2 was most predominant in glandular and luminal epithelial cells. However, on Days 3 and 4, stromal cells, and on Days 5 and 6, decidual cells appeared to be the predominant sites of synthesis of this growth factor. Uterine IGF-I gene expression was stimulated by ovarian steroids. Northern blot analysis showed that IGF-I transcripts were rare in the ovariectomized adult mouse uterus, but an injection of P and/or E caused a rapid accumulation of these transcripts. Analysis of the cell-specific expression of uterine IGF-I showed that E induced IGF-I gene expression primarily in epithelial cells, whereas P did so in the stroma. Superimposition of E on the P-primed uterus further stimulated IGF-I expression in the stroma. The results of these studies are consistent with an autocrine/paracrine function of uterine IGF-I, and indicate that ovarian steroids regulate the cell-specific and temporal patterns of expression of this gene in the peri-implantation mouse uterus.

Animals↗
PubMed1998

Expression of neu differentiation factor during the periimplantation period in the mouse uterus.

Complex cellular interactions occur between the blastocyst and the uterus during implantation. The expression of various polypeptide growth factors and their receptors in the uterus and/or blastocyst during the periimplantation period suggest that growth factors participate in the implantation process. Neu differentiation factor (NDF) is a member of the epidermal growth factor (EGF) family of growth factors and is represented by multiple conserved isoforms. The expression of several EGF-like ligands in the periimplantation uterus has been characterized, including EGF, heparin binding-EGF, transforming growth factor alpha, amphiregulin, betacellulin, and epiregulin. We analyzed the expression pattern of NDF in the periimplantation mouse uterus because of its mitogenic and differentiation-promoting effects. By using Northern analysis and isoform-specific polymerase chain reaction, we found that multiple isoforms are expressed in the periimplantation uterus. NDF displays a highly restricted temporal and spatial expression, with autoradiographic signals localized to the uterine stroma immediately surrounding the implanting blastocyst. NDF expression was absent in mice with delayed implantation but briefly reappeared with the same restricted distribution after termination of the delay by an injection of estrogen. Taken together, these results suggest that an activated blastocyst is required for the expression of NDF and that multiple isoforms may be involved in the complex network of cell-signaling events between the implanting blastocyst and the receptive uterus.

Animals↗
PubMed2000

Pregnancy and exogenous steroid treatments modulate the expression of relaxant EP(2) and contractile FP receptors in the rat uterus.

Prostaglandins (PGs) interact with specific receptors on plasma membranes to regulate myometrial activity in many species. The present study examined whether the expression of relaxant prostaglandin E receptor subtype two (EP(2)) and contractile prostaglandin F receptor (FP) mRNA in the rat uterus is changed during various states of pregnancy and regulated by steroid hormones. Expression of mRNA for EP(2) and FP receptors in the full-thickness uteri was analyzed by reverse transcription-polymerase chain reaction using specific primers. Abundance of receptor mRNA was expressed relative to beta-actin mRNA. Results showed that 1) mRNA for EP(2) receptors in the rat uterus was substantially increased during pregnancy (320%) compared with the nonpregnant state (100%, P < 0.01), and declined during labor at term (36% vs. 100% in control, P < 0.01); 2) mRNA expression for FP receptors in rat uterus was increased during pregnancy (333% vs. 100% in nonpregnant rats, P < 0. 01) and reached maximal levels during labor (515% vs. 100% in control, P < 0.01); 3) upon RU-486 treatment on Day 19 of pregnancy, uterine EP(2) receptor mRNA levels were decreased (18% vs. 100% in control, P < 0.01), and FP mRNA levels were increased (357% vs. 100% in control, P < 0.01); 4) with ICI 164384 (an antiestrogen) treatment on Day 19 of gestation, uterine FP receptor mRNA levels were decreased without effects on EP(2) receptors; 5) in ovariectomized (ovx) rats, progesterone increased EP(2) (163% vs. 100% in control, P < 0.01) and had no effects on FP receptor mRNA expression in the rat uterus; 6) estradiol increased FP receptor mRNA levels (358% vs. 100% in control, P < 0.01) and had no effects on EP(2) mRNA in the ovx rat uterus. Therefore, we conclude that steroid hormones modulate the mRNA for relaxant EP(2) and contractile FP receptors for PGs in the uterus and thus regulate uterine activity during pregnancy and labor.

Animals↗
PubMed2000

Estradiol-17beta inhibits nitric oxide synthase (NOS)-II and stimulates NOS-III gene expression in the rat uterus.

Nitric oxide (NO) is synthesized by NO synthases (NOS) from L-arginine in a variety of tissues, including rat uterus. Progesterone was shown to be required for maintaining elevated NOS II expression in pregnant rat uterus. However, effects of estrogens on uterine NOS II expression remains unclear. In the present study, we examined whether 17beta-estradiol regulates NO production and NOS II expression in the rat uterus during pregnancy and in nonpregnant rats treated with lipopolysaccharide (LPS). Rats on Day 18 of pregnancy received 17beta-estradiol (0.5 or 5 microgram/rat). Groups of ovariectomized (ovx) rats received 17beta-estradiol (5 microgram/rat) or LPS (1 mg/rat) or a combination of the two or received vehicle only. All rats were sacrificed 24 h after treatments. Nitrite concentrations in uterine cultures were measured by Greiss reaction. Uterine NOS II and NOS III proteins and mRNA levels were determined by Western blotting and reverse transcription polymerase chain reaction, respectively. In the pregnant rat, estradiol administration caused inhibition in total NO production, suppression of both mRNA and protein levels of NOS II enzyme, and increase in NOS III mRNA and protein levels in the uterus in a dose-dependent manner. The data indicate that estradiol inhibits NOS II and total NO generation and stimulates NOS III expression. In ovx rats, LPS stimulated NOS II mRNA and NO production by the uterus. Coadministration of 5 microgram estradiol profoundly suppressed NOS II mRNA and NO generation but elevated NOS III mRNA. Thus, estradiol inhibited LPS-induced increases in NOS II mRNA. Estradiol inhibits NO production by NOS II through the inhibition of NOS II expression in the rat uterus. This inhibition of NOS II expression occurs whether NOS II expression is constitutive (pregnancy) or induced (LPS-treated nonpregnant). Estradiol inhibition of NOS II expression occurs in the presence (pregnancy) or absence (ovx) of progesterone. Estradiol may play a role in regulating NOS II expression and NO production and uterine contractility during pregnancy and labor.

Animals↗
PubMed1976

New concepts on the action of oestrogens in the uterus and the role of the eosinophil receptor system.

Two receptor systems for oestrogens have been demonstrated in the uterus: the cytosol-nuclear receptor system and the eosinophil receptor system. It has been proposed that the cytosol-nuclear receptor system mediates the genomic response to oestrogens in the uterus, while the eosinophil receptor system is thought to mediate the uterine edema and other early oestrogenic responses in the uterus. Cortisol is known to decrease drastically the number of eosinophils in the blood and therefore to limit their availability for migration to the uterus. The present results show that cortisol also drastically reduces both the oestrogen-induced uterine eosinophilia and the uterine wet weight responses, but does not interfere with the oestrogen-induced uterine RNA and protein increases. Oestradiol-17 beta has a higher affinity than oestriol for the cytosol-nuclear receptors and is now found to be the more potent oestrogen in inducing the genomic activation in the uterus. Estriol has a higher affinity than oestradiol-17 beta for the eosinophil receptors, and therefore, oestriol is the stronger oestrogen in inducing those oestrogenic effects which are mediated by the eosinophil receptor system. We conclude that the eosinophil receptor system for oestrogens is a new system, independent of Jensen's cytosol-nuclear receptor system, and this eosinophil receptor system is involved in the mechanism of oestrogen action in the uterus.

Animals↗
PubMed1985

The effects of pregnancy and parturition on phosphorus metabolites in rat uterus studied by 31P nuclear magnetic resonance.

Concentrations of phosphorus metabolites and intracellular pH have been measured in non-pregnant, late-pregnant and post-partum rat uterus using 31P nuclear magnetic resonance (31P n.m.r.). Intact uterine tissue was superfused with oxygenated de-Jalon solution at 4, 20 or 37 degrees C while inside the n.m.r. spectrometer. The phosphocreatine concentration [PCr], was higher and the inorganic phosphate concentration [Pi], lower than values determined by chemical analysis of extracts from both pregnant and non-pregnant rat uterus. [PCr] was 1.4-fold greater in late-pregnant than in non-pregnant rat uterus. Following parturition, large changes were observed in [PCr], [Pi] and in an unidentified metabolite in the phosphomonoester (PME) region of the n.m.r. spectrum. The time course of the recovery of these metabolites to prepregnant values was determined. The [PCr] remained below the non-pregnant value for at least 1 week post-partum and the [Pi] was elevated, compared to the non-pregnant value, during this period. More rapid changes were seen in the [PME], which doubled on day 0 post-partum but almost returned to its non-pregnant value on day 1 post-partum. No significant difference was observed between intracellular pH values in late-pregnant and non-pregnant rat uterus; however, there was a large acid shift following parturition. Intracellular pH depended upon the temperature at which the tissue was maintained. The effect of muscular work during parturition was investigated by comparing Caesarian-sectioned uteri with uteri which had undergone normal parturition. Uteri examined 1 day after Caesarian operation showed no differences in metabolite levels from normal, 1 day post-partum uteri. We conclude that concentrations of phosphorus metabolites depend upon the physiological state of the uterus. We suggest that the changes following parturition are not a consequence of the mechanical work performed by the uterus, but must be caused by some other event associated with parturition such as hormonal changes.

Animals↗
PubMed1983

Uptake, receptor and biological response of estrone in the fetal uterus of guinea pig.

In vivo and in situ subcutaneous injection of 30 muCi of 3H-estrone (3H-E1) to guinea pig fetuses was carried out to study the dynamics of the selective uptake and retention of this estrogen in the uterus and other fetal organs. In the fetal uterus an increase in the uptake of radioactivity with time was found which was maximal 1 h after injection of 3H-E1. The analysis of radioactive material showed that in the fetal uterus unmetabolized 3H-E1 accounts for 65-75% of the total radioactivity between 10 and 60 min after the injection and its maximal concentration is 2.5-15 times and 10 times higher than the maximal concentrations found in other fetal organs and fetal plasma, respectively. Significant amounts of 3H-E1 were also present in lung (33-60% of the total radioactivity in this tissue), brain (37-52%) and ovary (18-47%), while an important conversion of 3H-E1 into 3H-estradiol was observed in the kidney (20-26%). Estrogen sulfates, essentially estrone sulfate, represented the greater part of the fetal plasma radioactivity (30-49%). 3H-E1-specific binding sites in the cytosol of the fetal uterus were found with physicochemical characteristics (specifically limited to natural and synthetic estrogens, Kd = 8.1 +/- 1.2 x 10(-10) M (SD), sedimentation coefficient 8S) similar to those of the typical estrogen receptor. The cytosol receptor-3H-E1 complex has a dissociation rate constant (K-1) of 16 +/- 0.7 x 10(-4) s-1 at 25 degrees C. The responsiveness of the fetal uterus to estrone treatment was studied after subcutaneous administration of estrone to pregnant guinea pigs (1 mg/kg/day for 3 consecutive days). Two biological responses were observed: an increase in fetal uterine weight (50-100% in relation to the nontreated animals) and a significant stimulation of progesterone receptor protein (10-16 times higher than in control animals). At the same time, there was a 50-70% decrease in the total estrogen receptor concentration. It is concluded that estrone could be involved in the biological responses to estrogen in the fetal uterus of guinea pig.

Animals↗
PubMed2006

Coordinated elevation of membrane type 1-matrix metalloproteinase and matrix metalloproteinase-2 expression in rat uterus during postpartum involution.

BACKGROUND: The changes occurring in the rodent uterus after parturition can be used as a model of extensive tissue remodeling. As the uterus returns to its prepregnancy state, the involuting uterus undergoes a rapid reduction in size primarily due to the degradation of the extracellular matrix, particularly collagen. Membrane type-I matrix metalloproteinase (MT1-MMP) is one of the major proteinases that degrades collagen and is the most abundant MMP form in the uterus. Matrix metalloproteinase-2(MMP-2) can degrade type I collagen, although its main function is to degrade type IV collagen found in the basement membrane. To understand the expression patterns of matrix metalloproteinases (MMPs) in the rat uterus, we analyzed their activities in postpartum uterine involution. METHODS: We performed gelatin zymography, northern blot analysis and immunohistochemistry to compare the expression levels of MT1-MMP, MMP-2, matrix metalloproteinase-9 (MMP-9) and the tissue inhibitors of MMPs-1 and 2 (TIMP-1 and TIMP-2) in the rat uterus 18 h, 36 h and 5 days after parturition with their expression levels during pregnancy (day 20). RESULTS: We found that both MT1-MMP and MMP-2 localized mainly in the cytoplasm of uterine interstitial cells. The expression levels of MT1-MMP and MMP-2 mRNAs and the catalytic activities of the expressed proteins significantly increased 18 h and 36 h after parturition, but at postpartum day 5, their mRNA expression levels and catalytic activities decreased markedly. The expression levels of MMP-9 increased 18 h and 36 h after parturition as determined by gelatin zymography including the expression levels of TIMP-1 and TIMP-2. CONCLUSION: These expression patterns indicate that MT1-MMP, MMP-2, MMP-9, TIMP-1 and TIMP-2 may play key roles in uterine postpartum involution and subsequent functional regenerative processes.

Animals↗
PubMed1982

Role of the nongravid part of the uterus in the regulation of corpus luteum function in pregnant rats.

The effect of the nongravid part of the uterus on corpus luteum (CL) activity was studied in rats bearing a single conceptus during midpregnancy. On day 7 (day 1 = insemination), the number of conceptuses was reduced to one by aspirating all but one conceptus (the aspiration group), by removing all of of the uterus except that containing a single conceptus (the hysterectomy group), or by aspirating conceptuses, as in the aspiration group, plus ligating the uterus, as in the hysterectomy group, but without removing the uterus (the sham hysterectomy group). Rats with a full complement of conceptuses (the intact control group) served as additional controls. Blood samples were obtained on days, 10, 12, and 15, to determine the effects of these procedures on the increase in serum progesterone that normally occurs between days 12 and 15 and to observe any related changes in serum LH between days 10 and 15. On day 15, the mean serum prgesterone concentrations and weights of the CL in the aspiration and sham hysterectomy groups were significantly lower than those in the intact control group. In the hysterectomy group, however, serum progesterone was even higher than in the intact control group, although the CL were significantly smaller than in the intact control group and were not different from those in the aspiration or sham hysterectomy groups. Serum LH on day 10 was significantly lower in the hysterectomy group than in any of the other groups; the latter were not significantly different from each other. By day 15, serum LH in the intact group had fallen to less than 50% of the value on day 10, while in the aspiration group, it remained as high as on day 10. In the hysterectomy group, there was no significant difference in serum LH concentrations between days 10 and 15. These results suggest that the nongravid part of the uterus inhibits progesterone secretion, and that in its absence, even a single conceptus can increase progesterone secretion after day 12 as much as can a full complement of conceptuses, but without also increasing the size of the CL. The uterus may exert this effect either through the pituitary or in cooperation with a pituitary factor, possibly LH.

Animals↗