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Congenital anomalies in the offspring of mothers with a bicornuate uterus.

BACKGROUND: Most of the reports on mothers with bicornuate uterus analyze fertility, reproductive capacity, and pregnancy outcomes. Very few of them, however, mention the risk for congenital anomalies in their offspring. Further, to our knowledge, no epidemiologic studies estimating the risk for congenital defects and analyzing the type of anomalies observed in infants born to mothers with bicornuate uterus have been reported. METHODS: Using a case-control study series, we estimated the risk of congenital anomalies in the offspring of women with a bicornuate uterus. To identify the specific defects associated with the presence of a bicornuate uterus in the mother, we analyzed 26 945 consecutive malformed infants from the Spanish Collaborative Study of Congenital Malformations and assessed the frequency of congenital anomalies in the offspring of mothers with a bicornuate uterus and in those born to mothers with a normal uterus. We then calculated the relative frequency, which is the quotient of the frequency of the individual defects in each group. This figure expresses the times each congenital defect is more frequent in infants of mothers with a bicornuate uterus than in those born to mothers with a normal uterus. RESULTS: Offspring of mothers with a bicornuate uterus had a risk for congenital defects four times higher than infants born to women with a normal uterus. The risk was statistically significant for some specific defects such as nasal hypoplasia, omphalocele, limb deficiencies, teratomas, and acardia-anencephaly. CONCLUSIONS: Offspring of mothers with bicornuate uterus are not only at high risk for deformations and disruptions, but also for some type of malformations.

Case-Control Studies↗

Dominant expression of porcine Calbindin-D9k in the uterus during a luteal phase.

Calbindin-D9k (CaBP-9k) is a member of intracellular calcium binding proteins, which have a high affinity to calcium. CaBP-9k is mainly expressed in the mammalian intestine, uterus and placenta, and is regulated in tissue- and species-specific manners. Previous studies have shown that CaBP-9k expression is mainly controlled by steroid hormones and their receptors. Thus, we further investigated the expression and regulation of CaBP-9k during an estrus cycle in the pig uterus by Northern blot and immunoblot analysis in this study. In addition, serum levels of estrogen (E2) and progesterone (P4) were measured using ELISA. The CaBP-9k mRNA is highly expressed in the porcine uterus during a luteal phase compared to a follicular phase, and its mRNA level in a luteal phase is increased up to 10-fold compared to a follicular phase. In parallel to the level of CaBP-9k mRNA, the CaBP-9k protein is also dominantly expressed in the porcine uterus, and strongly expressed in the epithelium and glands of the porcine uterus during a luteal phase. Although, the localization of the CaBP-9k protein is scarcely detected at follicular phase, it is dominantly expressed in the porcine uterus during a luteal phase. In addition, the serum P4 level was significantly increased during a luteal phase compared to a follicular phase, whereas no difference was observed in E2 levels between follicular and luteal phases, indicating that the ratio of P4/E2 is remarkably increased in porcine uterus during a luteal phase compared to a follicular phase. In conclusion, these results suggest that P4 may play an important role in the up-regulation of CaBP-9k gene in the porcine uterus in a luteal phase, which is unlike the condition in the rat uterus. In addition, the porcine CaBP-9k may be dominantly expressed in the epithelium and glandular structure of pig uterus during a luteal phase. It may also be differentially regulated during this cycle presumably by steroid hormones, especially up-regulated P4 levels in this tissue.

Animals↗

Prostaglandin release from the guinea-pig uterus superfused in vitro. Effect of stage of estrous cycle, progesterone, estradiol, oxytocin and A23187.

Prostaglandin (PG) E2 was the major PG released from the superfused guinea-pig uterus on Day 7, followed by in descending order 6-oxo-PGF1 alpha, thromboxane (TX) B2 and PGF2 alpha. However, the outputs of all four substances were low and were very similar. By Day 15, PGF2 alpha output from the superfused uterus had increased 21.9-fold, whereas the outputs of PGE2, 6-oxo-PGF1 alpha and TXB2 had increased only 1.8-, 2.9- and 1.2-fold, respectively. A mechanism is apparently "switched on" between Days 7 and 15 which causes a fairly specific increase in the release of PGF2 alpha from the uterus. Progesterone and/or estradiol had no effect on PG or TX release when superfused over the uterus on Day 7, nor did they have any effect on PG and TX release from the Day 15 uterus when administered separately. When administered together, however, they significantly inhibited PGF2 alpha, PGE2 and 6-oxo-PGF1 alpha, but not TXB2, release from the Day 15 uterus. Oxytocin had no effect on PG release from the Day 7 or Day 15 uterus, while A23187 stimulated PGF2 alpha, 6-oxo-PGF1 alpha and, to a lesser extent, PGE2 release from the uterus on both Days 7 and 15. Oxytocin is apparently not important for stimulating PGF2 alpha release from the guinea-pig uterus in relation to luteolysis, whereas increasing intracellular free Ca++ levels may be part of the mechanism for "switching on" uterine PG synthesis. Furthermore, changes in intracellular free Ca++ levels in the endometrium may be responsible for the pulsatile nature of PGF2 alpha release from the uterus.

Animals↗

Alteration in the collagen content of the human uterus during pregnancy and post partum involution.

Quantitative collagen determinations demonstrate an increase of approximately 800 per cent in the collagen content of the human uterus at term as compared with the non-pregnant state. Following parturition, there is a rapid resorption of collagen. The amount of collagen which disappears from the post partum uterus is approximately 53 gm. By the 8th day post partum, the human uterus has lost approximately 72 per cent of the total collagen which was present at term. The slopes of curves depicting alterations in collagen content of the uterus of the rat and human are virtually identical, despite the marked differences in the length of the gestational periods of the two species. The alterations in the collagen content of the human uterus during pregnancy and involution closely follow changes in total uterine weight. There is a slight decrease in per cent collagen content of the uterus during pregnancy, and an increase in the water content of the post partum uterus. Approximately 97 per cent of the collagen which is present in the human uterus at term is of the so called "insoluble" type. The physiological resorbability of uterine collagen, as evidenced by its post partum dissolution, cannot therefore be correlated with its in vitro solubility characteristics. No collagenase was demonstrable in the myometrium of post partum uteri. A 2 day post partum uterus was found to contain an enzyme which slowly degraded gelatin at pH 3.85 but was virtually inactive at pH 7,0. There is an increase in myometrial prolidase activity of approximately 75 per cent, commencing 2 days post partum. Prolidase activity remains elevated until the 8th day post partum, and subsequently falls to almost normal levels by the 5th post partum week. During the process of involution, the post partum uterus shows histological evidence of edema and partial destruction of its reticular framework.

Animals↗

Control and assessment of the uterus and cervix during pregnancy and labour.

Preterm labour and resultant preterm birth are the most important problems in perinatology. Countless efforts have failed to establish a single effective treatment of preterm labour, partly because the mechanisms regulating the uterus and cervix during pregnancy are not well understood. New knowledge is needed to inhibit early progression of labour (uterine contractility and cervical ripening), and adequate quantitative tools to evaluate the uterus and cervix during pregnancy are lacking. In this review, we outline studies showing that the uterus (myometrium) and cervix pass through a conditioning step in preparation for labour. This step is not easily identifiable with present methods to assess the uterus or cervix. In the uterus, this seemingly irreversible step consists of changes in the electrical properties to make muscle more excitable and responsive to produce forceful contractions. In the cervix, the step consists of softening of the connective tissue components. Progesterone appears to have a dominant role in controlling both the uterus and cervix, as antiprogestins induce early, preterm conditioning leading to preterm labour. Apparently, nitric oxide (NO) also controls conditioning of the uterus and cervix. In the uterus, NO, in concert with progesterone, inhibits uterine contractility. At term, NO production by the uterus and placenta are decreased and allow labour to progress. In contrast, NO in the cervix increases at the end of pregnancy and it may be the final pathway for stimulating cervical ripening by activation of metalloenzymes. The progress of labour can be assessed non-invasively using electromyographic (EMG) signals from the uterus (the driving force for contractility) recorded from the abdominal surface. Uterine EMG bursts detected in this manner characterize uterine contractile events during human and animal pregnancy. A low uterine EMG activity, measured transabdominally throughout most of pregnancy, rises dramatically during labour. EMG activity also increases substantially during preterm labour in humans and rats. This method may be used one day to predict impending preterm labour and identify control steps and treatments. A quantitative method also assesses the cervix, using an optical device which measures collagen fluorescence in the cervix. The collascope estimates cervical collagen content from a fluorescent signal generated when collagen cross-links are illuminated with excitation light of about 340 nm. The system has proved useful in rats and humans at various stages of pregnancy, and indicates that cervical softening occurs progressively in the last one-third of pregnancy. In rats, collascope readings correlate with resistance measurements made in the isolated cervix, which may help to assess cervical function during pregnancy, and indicate control and treatments.

Animals↗

[Ultrasonic assessment of the development of the uterus in childhood].

In 150 girls from the newborn period up to the 18. year the size of the uterus was measured by sonography. In all children the length, width, depth and volume of the uterus as well as its shape and other signs of development were determined. In the newborn period and in the following first months of life an estrogen stimulated uterus with the shape of a drop could be shown. The size of the uterus decreased till the end of the first year. The length of the uterus in the neonatal period was 4.0 +/- 0.5 cm, the volume was 3.6 +/- 1.9 cm3. In the following rest phase up to the age of 8 years the length of the uterus was 2.8 +/- 0.4 cm and the volume was 1.2 +/- 0.4 cm3. The shape of the uterus in this age group was tubular. One to two years before secondary pubertal signs could be shown, sonography already demonstrated the beginning of pubertal uterus growth. In the postpubertal period the uterus had the typical pear shape with a corpus/cervix-relation of 2:1. In the postpubertal period the length was 6.8 +/- 1 cm with a volume of 33 +/- 22 cm3. The knowledge of the normal developmental dates of the uterus in children is essential for the diagnosis of malformations and tumours of the pelvis, but also for the diagnosis of distorted puberty such as pubertas praecox, pubertas tarda, amenorrhea and growth retardation.

Adolescent↗

[The effect of estradiol, norethisterone and testosterone on regional circulation and relative weight of the testes, ovaries and uterus in rats].

In nine experiments of 188 rats (85 males and 103 females), relative weight and local blood flow (with 85Sr-microspheres) was estimated in testes, ovaries and uterus after the administration of estradiol benzoate (Agofollin Depot 1 mg per rat or 5 mg per kg s.c. in time intervals of 3 to 7 days), norethisterone (Norethisterone tablets 0.01 or 0.02% in the food) or testosterone (Agovirin Depot 25 mg per kg s.c. every 5 days); all preparations were administered for four weeks. With one exception (norethisterone in males), the results of two experiments performed in the same manner are presented in every experimental situation. After estradiol, the body weight of rats in both sexes is lowered, relative weight of the uterus increased. The local circulatory indicators i.e. 85Sr-microsphere uptake in % dose per g, blood flow in (ml.min-1).g-1 and organ flow fraction % of cardiac output are decreased in the testes and unchanged on the ovaries. As regards the uterus, in the first experiment the 85Sr-microsphere uptake and the blood flow is significantly lower, in the second experiment these values remain unchanged and flow fraction is increased due to enlargement of the uterus. Norethisterone lowers the body weight and relative weight of the testes; in one experiment it increases relative weight of the uterus. Local circulatory indicators are decreased in the testes and inconstantly in the ovaries, whereas in the uterus the decreases are insignificant. Testosterone does not change the body weight. In one experiment, it increases the cardiac output per 100g of body weight; relative weight of the testes is lowered in one experiment and in the ovaries in both experiments, and markedly increased in the uterus. Local circulatory indicators were decreased in the testes, ovaries and uterus but approximately one half of the differences are significant. Thus, with one exception, all statistically significant local circulatory changes after the administration of the hormonal preparations are decreasing; the suppressive action is evident in the local circulation in sexual organs of the animals of the corresponding sex as well as in animals of the other sex. The suppression of the local circulation in testes and ovaries is probably in connection with endocrine regulations; the decrease of microsphere uptake and blood flow per g in the uterus may participate in insufficient adaptation of the blood supply in the enlargement of the uterus after four weeks' administration of estradiol and testosterone.

Animals↗

Sympathetic innervation of the upper and lower regions of the uterus and cervix in the rat have different origins and routes.

The origins and routes of the postganglionic sympathetic nerve supply to the upper and lower uterus and to the cervix were investigated in the rat by using denervation procedures combined with immunohistochemistry and retrograde tracing. The sympathetic nerve fibers of the upper part of the uterus arise from the ovarian plexus nerve. They mainly originate (90%) from neurons of the suprarenal ganglia (SRG) and of the T10 to L3 ganglia of the paravertebral sympathetic chain. Fluoro-Gold injections into different regions of the upper uterus showed that the SRG neurons mainly provide innervation to the tubal extremity (52%) rather than to the uterine portion below this area (26%). Very few neurons of the celiac ganglion or the aorticorenal ganglia participated in this innervation. Most of the sympathetic innervation of the lower uterus and the cervix (90%) originates from neurons of the paravertebral ganglia T13 to S2, principally at the L2-L4 levels. By using immunocytochemistry, we show that very few tyrosine hydroxylase-positive neurons of the pelvic plexus project to these areas, where they represent only 3% of the sympathetic nerve supply. Again, very few neurons of the inferior mesenteric ganglion (IMG) supply the lower uterus and the cervix. The comparison between retrograde tracing experiments in intact animals and after the removal of the IMG shows that very few sympathetic postganglionic axons from the paravertebral chain pass through the IMG to reach the lower uterus and the cervix. In contrast, these axons mainly project to splanchnic nerves bypassing the IMG to connect with the hypogastric nerves. In addition, some axons supplying the lower uterus follow the superior vesical arteries and then reach the organ. Taken together, these results show that the upper region of the uterus receives a sympathetic innervation that is different in origin and route from that of the lower uterus and the cervix. Such a marked region-specific innervation suggests that nerve control of the myometrial activity may be functionally different between the oviduct and the cervical ends of the uterus.

Animals↗

Comparison of vasopressin and oxytocin receptors in the rat uterus and vascular tissue.

Several studies indicate that oxytocin and vasopressin receptors in the human uterus are heterogeneous. We have investigated whether oxytocin and vasopressin bind to separate receptors in the day 21 and day 22 pregnant rat uterus and whether uterine vasopressin receptors are the same as the vascular V1A subtype. In isolated organ bath experiments we showed that the potency of d(CH2)5[Tyr(Me)2]vasopressin to inhibit vasopressin contraction in rat aorta was different from that in the day 21 pregnant uterus. Saturation curves of [3H]vasopressin in membranes from cultured aortic myocytes and pregnant uterus were linear and yielded the same 1 nM Kd values. However, the potency of d(CH2)5[Tyr(Me)2]vasopressin and of [Thr4,Gly7]oxytocin at antagonizing [3H]vasopressin confirmed the differences between the vascular smooth muscle and uterine vasopressin receptor. The peptides had respectively higher and lower affinity for aortic cell sites than for uterine sites. It was more difficult to distinguish pharmacological differences for oxytocin and vasopressin receptors in the uterus. On day 22, the high affinity of [Thr4,Gly7]oxytocin and oxytocin for both [3H]oxytocin and [3H]vasopressin binding sites was consistent with the notion that the uterus expresses essentially oxytocin receptors at this stage of gestation. However, oxytocin, vasopressin and three analogs showed a different potency for inhibiting [3H]oxytocin and [3H]vasopressin binding on day 21 versus day 22 of gestation. We conclude that in the rat uterus vasopressin binds to a receptor that is different from the vascular V1A subtype. Also, the binding sites for [3H]vasopressin and [3H]oxytocin on day 21 uterus membranes do not resemble the classical oxytocin receptor as described in the literature suggesting that on day 21 vasopressin and oxytocin bind in the uterus to a receptor that might be different from those currently characterized.

Animals↗

The effects of progesterone, prostaglandin F2alpha and oxytocin on the calcium-activation of the uterus.

The relationship between "activator-calcium" (A-Ca), progesterone (P), prostaglandin F2alpha (PGF2alpha) and oxytocin (Oxy) has been examined in 100 uterine strips of 34 pregnant and 100 strips of 34 post partum rabbits. At the 25th day of gestation, uterine P was 13.9+/-1.3 ng/g, while within 3-12 hours post partum 3.3+/-0.3 ng/g tissue (P less than 0.001). Uterine strips, mounted isometrically in Krebs' solution, sustained maximum excitability in a steady state when exposed every 30 seconds for 4 seconds to an electric field of 12 V/5 cm (a.c.). The maximally contracting muscles were then rinsed at intervals of 6 minutes with Ca-free Krebs. In Ca-free Krebs, the post partum uterus lost 31% of its Ca and 96% of its excitability in a short 25 minutes, while the pregnant uterus lost 30% of its Ca and 93% of its excitability in 50 minutes (P less than 0.001). Since the extracellular space is approximately 30% in the uterus, this approximately 30% Ca, lost by both muscles, most probably was extracellular Ca and the small A-Ca fraction which is presumably "bound" more strongly at the membrane systems of the P-dominated pregnant, than the non-dominated post partum uterus. The significantly faster and more complete recovery from Ca-deficiency and inexcitability of the pregnant than the post partum uterus (P less than 0.001), at different levels of external Ca, further substantiates this premise. So does the demonstration that exposure to Ca-free Krebs increases 45Ca-efflux 400% in the post partum and only 110% in the pregnant uterus (P less than 0.001). Exposure to 100 ng/ml PGF2alpha in normal Krebs has a similar effect on the 45Ca-efflux of the post partum uterus, while the response of the pregnant uterus is indistinct (P less than 0.001). These highly significant differences between the post partum and the pregnant uteri in their Ca-efflux explain the higher threshold (P less than 0.001) and lower "sensitivity" to PGF2alpha and Oxy (P less than 0.001) of the pregnant than the post partum uterus. The already very highly significant differences between the two muscles, in threshold and sensitivity to these two most potent oxytocics, were increased still further by rendering the uterine strips Ca-deficient. All together, these findings substantiate the early contention (1-7, 18, 19) that uterine function at the cellular level is regulated by opposing actions of the suppressor P and the intrinsic stimulant PG or other oxytocic agents on threshold, excitability and the Ca-activation of the contractile process.

Animals↗

A novel complementary deoxyribonucleic acid is abundantly and specifically expressed in the uterus during pregnancy.

OBJECTIVE: Our purpose was to identify novel genes expressed by the uterus during late pregnancy. STUDY DESIGN: A complementary deoxyribonucleic acid library constructed from late pregnancy mouse uterus was screened by differential hybridization with complementary deoxyribonucleic acid probes constructed from late pregnancy mouse uterus and nonpregnant mouse uterus. Radiolabeled complementary deoxyribonucleic acid probes derived from one of the complementary deoxyribonucleic acids isolated were used in northern hybridizations against ribonucleic acid collected from pregnant and nonpregnant uterus and a variety of other mouse tissues. RESULTS: A total of 40 positive clones were isolated; half were identified as cytotoxic T-lymphocyte antigen-2 alpha (a putative inhibitor of the protease cathepsin L) and the other half represented a novel complementary deoxyribonucleic acid. Conceptual translation of the complementary deoxyribonucleic acid predicted a novel protein of 154 amino acids that is proline rich and acidic (pregnancy-specific uterine protein). Northern hybridizations demonstrated that message is abundant in the uterus during late pregnancy. After birth expression rapidly decreased and message was no longer found in the uterus by the third day. A minimal amount of message is present in placental ribonucleic acid, but expression is otherwise not detected in a variety of adult and fetal tissues surveyed, suggesting that expression of this gene is limited to the pregnant uterus. CONCLUSIONS: The abundance of message and expression apparently limited to the pregnant uterus suggests that the protein represented by this complementary deoxyribonucleic acid may play an important role in pregnancy.

Animals↗

Uterus transplantation.

Until recently, only life and death situations warranted organ transplantation. Nonvital transplantation, to further a patient s wishes and goals, was not considered justified. It can be argued, however, that this distinction is not morally significant. Patients with kidney failure, for example, can be kept alive by dialysis. But their quality of life would be greatly enhanced by kidney transplant, which is thus considered a justified procedure. So a spectrum of rationales may justify transplantation. Transplantation of the uterus would relieve the anguish of women who greatly desire to conceive a child. Some women do not have a uterus. In some cases this is due to a congenital absence (Rokitansky s syndrome). In other cases, surgical removal of the uterus was required to repair an obstetrical rupture. With a transplanted uterus, many of these women could have the opportunity to become pregnant as a result of nonvital organ transplant. While other organ transplant donations most often come from cadavers and less often from living donors (kidney or partial liver), the donor source for a uterus may be an otherwise healthy living patient who requires uterus removal as a standard care procedure. Furthermore, it should be possible to remove the transplanted uterus from the recipient after successful pregnancies, so the patient would not be subjected to lifelong antirejection medications. Since animal uterus transplantation has been done successfully, human uterus transplantation might be considered for select cases. One such case has been reported.

Animals↗

[Epidemiological aspects of children of women with bicornuate uterus].

BACKGROUND: Most published papers on women with a bicornuate uterus analyze their fertility problems, as well as certain pregnancy complications. We have not found any epidemiological study on the infants of mothers with this uterine malformation. Only in some papers a reference is made about the relationship of maternal bicornuate uterus with congenital deformations and disruptions in their infants. PATIENTS AND METHODS: Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), which has a case-control methodology, some characteristics in a series of 26,945 malformed infants, such as birth weight, sex, gestational age, umbilical cord length, placental weight and maternal age, were analyzed by separating infants of mothers with normal uterus and those of mothers with a bicornuate uterus. RESULTS: Results showed that women with a bicornuate uterus have more daughters than sons and an increased risk for intrauterine growth retardation and prematurity with respect to infants of mothers with a normal uterus. On the other hand, the risk of having an infant with congenital defects is higher for women with a bicornuate uterus than for those with a normal uterus. CONCLUSIONS: Pregnancies of women with a bicornuate uterus have to be considered at risk since they have more risk for complications and for having an infant with congenital defects, premature birth and with intrauterine growth retardation.

Case-Control Studies↗

Cyclooxygenase and lipoxygenase pathways in the preimplantation rabbit uterus and blastocyst.

We have measured by radioimmunoassay the concentration and production of 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), a metabolite in the lipoxygenase pathway, and PGs in different uterine compartments, and blastocysts during the preimplantation period in the rabbit. The production is defined as the synthesis minus the metabolism for a defined period of time. The pattern of uterine PGF production on days 5-6.5 was quite similar for the whole uterus and the myometrium showing a peak production on Day 6. The concentration and production of PGF were always higher in the endometrium. While significant production of PGE was noticed in the whole uterus on days 5-6 and in the myometrium on Day 6, the endometrium showed some production on these days. On the contrary, absolutely no production of this PG was observed in the endometrium on Day 6.5. The concentration and production of 6-keto-PGF1 alpha were always lower in the endometrium than those observed in the myometrium or the whole uterus. While highest production of this PG was found to be on Day 6.5 in the whole uterus and on Day 5 in the endometrium, the production in the myometrium remained constant on all days examined. The production of 5-HETE in the endometrium was noticeable on Days 5-6.5, in the whole uterus on Days 5 and 6.5, and in the myometrium only on Day 6.5. However, the concentrations of 5-HETE showed a tendency to be higher at 2 h than at 0 h in these compartments on Days 5-6.5. Furthermore, a linear increase in 5-HETE levels both at 0 h and 2 h was observed in the endometrium on Days 5-6.5; no such difference in mean 5-HETE level was noted in the whole uterus or myometrium on any of these days. The production of 5-HETE in the blastocyst was noted only on Day 5. The results not only demonstrate the presence of both the cyclooxygenase and the lipoxygenase pathways in the preimplantation rabbit uterus and blastocyst, their differential operation in various compartments of the uterus on various days of early pregnancy suggests an integrated role for these mediators in embryo-uterine interaction during implantation.

6-Ketoprostaglandin F1 alpha↗

Effects of hydrocortisone, oestradiol and progesterone on A23187-stimulated prostaglandin output from the guinea-pig uterus superfused in vitro.

Hydrocortisone (10 micrograms/ml) had no effect on the basal outputs and A23187-stimulated outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha from the Day 15 guinea-pig uterus superfused in vitro. These findings indicate that the high output of PGF2 alpha from the guinea-pig uterus during the last one-third of the oestrous cycle is not modulated by the adrenal glucocorticoid hormones. Progesterone (10 micrograms/ml) had no effect on the A23187-induced increases in PG output from the Day 15 guinea-pig uterus. However, oestradiol (10 micrograms/ml but not 1 microgram/ml) significantly reduced the increases in outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha induced by A23187 from the Day 15 guinea-pig uterus, without affecting basal PG outputs. The increase in uterine tone induced by A23187 in the Day 15 guinea-pig uterus was reduced by 20-50% by oestradiol (10 micrograms/ml). The addition of oestradiol (10 micrograms/ml) and progesterone together (10 micrograms/ml) produced the same effects on the Day 15 guinea-pig uterus as oestradiol alone. Oestradiol (10 micrograms/ml) also reduced the A23187-induced increases in PG output from the Day 7 guinea-pig uterus, but did not reduce the increase in uterine tone. Oestradiol (10 micrograms/ml) reduced the increases in outputs of PGF2 alpha, PGE2 and 6-keto-PGF1 alpha induced by exogenous arachidonic acid from the Day 7 and Day 15 guinea-pig uterus. Previous studies have shown that oestradiol is not a cyclo-oxygenase inhibitor. The present findings suggest that oestradiol, at a relatively high concentration, may interfere with the access of arachidonic acid to the cyclo-oxygenase enzyme. This action of oestradiol may explain its anti-luteolytic action when administered to guinea-pigs in large doses after Day 9 of the cycle.

6-Ketoprostaglandin F1 alpha↗

Genistein alone and in combination with the mammalian lignans enterolactone and enterodiol induce estrogenic effects on bone and uterus in a postmenopausal breast cancer mouse model.

The use of phytoestrogens, such as isoflavones and lignans, for treatment of postmenopausal breast cancer is increasing, but their effects on bone and other major organs are not clear. While the isoflavone genistein (GEN) has been shown to prevent or slow the loss of bone mineral density (BMD), the effect of lignans enterodiol (END) and enterolactone (ENL) are unknown. In this study, we determined in ovariectomized mice with human MCF-7 breast tumor xenografts the effects of the lignans, and GEN, alone and in combination, on bone and uterus. Mice with established MCF-7 tumors were fed a basal diet (AIN-93G), divided into 5 groups, and given daily subcutaneous injections (10 mg/kg body weight) of either ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. Results showed that GEN acts estrogenically in both the uterus and bone by increasing the uterus weight, femur BMD, and femur biomechanical strength (yield load), while the lignans do not. However, treatment with MIX induced minimal effects on femur biomechanical strength parameters but significantly increased uterus weight. A significant positive correlation was observed between MCF-7 tumor volume and femur BMD and biomechanical strength parameters (femur peak load and yield load) but not with uterus weight, suggesting that the uterus may respond differently to phytoestrogens compared to MCF-7 tumors and bone. It is concluded that GEN induces beneficial effects on bone but has adverse effects on tumors and uterus in this model of postmenopausal breast cancer. The lignans do not exert adverse effects on any tissue, however, when combined with GEN, they exert an adverse effect on the uterus.

4-Butyrolactone↗

Anatomical development of the fetal uterus.

OBJECTIVE: The objective of this study was to gather data on the morphology of the uterus during its development, to provide detailed information regarding the neighboring structures and its variations using anatomical dissections. STUDY DESIGN: Eighty uteri acquired from female fetuses aged 10-40 weeks of gestation were used in this study. Firstly, the relationship between the fetal uterus and the linea terminalis and the position of the uterus within the pelvic cavity was noted. Then the distance between the fundus of the uterus to the promontory and pubic symphysis were measured. Fetal uteri were classified according to their physical appearances. Finally the lengths of the corpus and cervix in three planes and the anteflexion angle were measured. RESULTS: During the fetal period, the fundus of the uterus was above the linea terminalis in 94% and below it in 6% of the cases. The distance between the fundus of the uterus and the promontory significantly correlated with the distance between the fundus of the uterus and the pubic symphysis (p<0.001). This was true for the correlation between the gestational age and the orthogonal lengths of the uterine corpus and cervix (p<0.001). As the gestational age advanced, the anteflexion angle was noted to reduce from 177 degrees to 120 degrees . The shape of the uterus was either cylindrical, pear-shaped, heart-shaped or hourglass-shaped during the fetal period. CONDENSATION: We believe that the data obtained through dissections of the human fetuses in this study will help identifying uterine developmental variations, anomalies and pathologies and will contribute to the studies carried out in obstetrics, perinatology, forensic medicine and fetal pathology departments.

Body Weights and Measures↗

Ultrasonic evaluation of the uterus and uterine cavity after normal, vaginal delivery.

OBJECTIVE: To describe uterine and uterine cavity changes throughout the puerperium, as revealed by ultrasound. METHODS: This was a prospective, longitudinal study in which 42 women with uncomplicated vaginal term deliveries were examined serially by ultrasound on postpartum days 1, 3, 7, 14, 28 and 56. The first four examinations were performed transabdominally and the last two transvaginally. The involution process of the uterus was assessed by measuring the anteroposterior diameter of the uterus and uterine cavity. Morphological findings were recorded. The influence on the involution process of parity, breast-feeding, maternal smoking and infant's birth weight were also evaluated. RESULTS: The maximum anteroposterior diameter of the uterus diminished substantially and progressively from 92.0 mm on day 1 postpartum to 38.9 mm on day 56. The maximum anteroposterior diameter of the uterine cavity diminished from 15.8 mm on day 1 to 4.0 mm on day 56. However, the anteroposterior diameter of the uterine cavity, 5 cm from the fundus, typically increased on days 7 and 14 postpartum. The position of the uterus and the shape and the appearance of the cavity change in a unique way during the normal puerperium. The uterus was most often retroverted and empty in the early puerperium. Fluid and debris in the whole cavity were seen in the middle part of the puerperium. In late puerperium the cavity was empty and appeared as a thin white line. Endometrial gas was occasionally visualized. No correlation was found between the involution of the uterus and parity, breast-feeding and the infant's birth weight. CONCLUSION: Transabdominal sonography is suitable for examination of the uterus during the first 14 days postpartum but from day 28 the transvaginal route is preferable. The uterine body and position, as well as the cavity, are easy to examine by ultrasound. Accumulation of fluid and debris in the uterine cavity is a common and insignificant finding of the involuting uterus. It is located in the cervical area in the early puerperium and in the whole uterine cavity in the middle part of the puerperium. Findings from uncomplicated vaginal deliveries are needed as a reference when the diagnostic efficacy of ultrasound for pathological conditions is to be tested.

Adult↗