Molecular cloning of two Rab family proteins, S2 and S10

Diverse lines of evidence suggest that the Fallopian tubes make no overwhelming contribution to human reproduction other than as a conduit for gametes and embryos. Even so, bearing in mind global success rates for in vitro fertilization (IVF) coupled with uterine transplantation of embryos (20% fruitful pregnancies), the Fallopian tubes may make a subtle contribution to reproductive performance. The experimental evidence from monkeys and man arguing against an essential r?le for the tubes -- at least in individual instances -- would include (1) the results of Estes' operation, when ovaries are autotransplanted into the uterine lumen in women with blocked or missing Fallopian tubes and pregnancy ensues; (2) asynchronous embryo transfer when newly fertilized (pronucleate) eggs transplanted to the uterus can generate a pregnancy; (3) the transcervical transfer after IVF of early cleavage stage human embryos into the uterus, with subsequent establishment of pregnancy; (4) the trans-cervical transfer of human spermatozoa and oocytes into the uterus to give pregnancy, indicating that capacitation, fertilization and the earliest stages of embryonic development can be achieved in the uterus. In endeavoring to explain contrasts between these successful procedures in primates and their failure in non-primates, perhaps the simplex uterus in primates compared with a bicornuate or bipartite uterus in laboratory and farm species has relevance: there is lack of a clear-cut distinction between the endometrium and endosalpinx in the intra-mural segment and potential mixing of uterine and tubal fluids. Indeed, the latter may explain in part a susceptibility to tubal ectopic pregnancy, coupled with proliferating endometrial fragments in the Fallopian tube.     

Inner ear and maternal reproductive defects in mice lacking the Hmx3 homeobox gene

The Hmx homeobox gene family is of ancient origin, being present in species as diverse as Drosophila, sea urchin and mammals. The three members of the murine Hmx family, designated Hmx1, Hmx2 and Hmx3, are expressed in tissues that suggest a common functional role in sensory organ development and pregnancy. Hmx3 is one of the earliest markers for vestibular inner ear development during embryogenesis, and is also upregulated in the myometrium of the uterus during pregnancy. Targeted disruption of the Hmx3 gene results in mice with abnormal circling behavior and severe vestibular defects owing to a depletion of sensory cells in the saccule and utricle, and a complete loss of the horizontal semicircular canal crista, as well as a fusion of the utricle and saccule endolymphatic spaces into a common utriculosaccular cavity. Both the sensory and secretory epithelium of the cochlear duct appear normal in the Hmx3 null animals. The majority of Hmx3 null females have a reproductive defect. Hmx3 null females can be fertilized and their embryos undergo normal preimplantation development, but the embryos fail to implant successfully in the Hmx3 null uterus and subsequently die. Transfer of preimplantation embryos from mutant Hmx3 uterine horns to wild-type pseudopregnant females results in successful pregnancy, indicating a failure of the Hmx3 null uterus to support normal post-implantation pregnancy. Molecular analysis revealed the perturbation of Hmx, Wnt and LIF gene expression in the Hmx3 null uterus. Interestingly, expression of both Hmx1 and Hmx2 is downregulated in the Hmx3 null uterus, suggesting a hierarchical relationship among the three Hmx genes during pregnancy.     

MR imaging of the uterus: findings from high-resolution multisection dynamic imaging with a surface coil

MR imaging of the female pelvis with a local coil (multiple phased array coils) has been reported. With this method, the signal-to-noise ratio (S/N) is improved so that high-resolution images can be obtained. Dynamic contrast-enhanced MR imaging has been reported to be useful in diagnosing uterine neoplasms. However, dynamic MR imaging is done in only limited imaging planes. When multisection dynamic MR imaging with fast gradient-echo sequences is combined with the use of a local coil, high-resolution images can be obtained throughout the entire uterus during a single breath-hold. This pictorial essay illustrates the appearance of the normal uterus and malignant uterine neoplasms on high-resolution multisection dynamic MR images obtained with a Helmholtz-type surface coil.     

The influence of taking uterine biopsies on the concentration of some steroids in the blood and in the uterus, on the ovarian activity, and on the sexual behaviour of the mare

It has been shown that stimulation of the uterus of mares by the daily taking of biopsies can result in the occurrence of oestrous symptoms. This is accompanied by some follicular growth and a progesterone content in the blood often higher than 1 ng/ml. The following observations suggest that this progesterone originates in the uterus and not in the ovaries: (1) no active corpora lutea appeared to be present in the ovaries after ovariectomy, (2) ovariectomized mares showed the same oestrous symptoms in similar experiments and even mating took place, (3) in the uterine biopsies the concentration of the compound referred to as "5.4", which is assumed to be easily convertible into progesterone, had already increased considerably in the second biopsy, (4) administration of stilboestrol reduced the rise of the progesterone level in the uterine biopsies as well as in the blood. The absence of oestradiol-17 beta in the ovarian follicles and the fact that ovariectomized mares also come into heat suggest that oestrogens cannot be held responsible for the oestrous symptoms in these mares. Our experiments demonstrate that the uterus can be involved in sexual behaviour and the formation of steroids.     

Immunohistochemical studies on the expression and estrogen dependency of EGF and its receptor and C-fos proto-oncogene in the uterus and vagina of normal and neonatally estrogen-treated mice

BACKGROUND: The final target cell response to estrogen is dependent not only on the estrogen receptor, but also on autocrine/paracrine interactions with growth factors (e.g., EGF) and proto-oncogenes (e.g., c-fos). Because neonatal estrogen treatment results in permanent changes in the female mouse genital tract (permanent vaginal cornification, cervical adenosis and tumors, changed growth control mechanisms in uterus), it was of interest to study possible acute and permanent effects of such treatment on distribution and levels of EGF, its receptor (EGF-r), and c-fos and to relate such changes to morphological development and appearance of epithelial abnormalities. METHODS: Immunohistochemical techniques using frozen sections from the uterus and vagina of neonatal and adult (ovariectomized, estradiol-treated) females, treated with olive oil or diethylstilbestrol in neonatal life. RESULTS: A difference in stromal-epithelial distribution of EGF was demonstrated with respect to region studied (uterus, vagina) and age (neonatal, adult). EGF was localized mainly in the uterine stroma but in both vaginal epithelium and stroma (with a different pattern compared to uterus). In neonatal females, EGF occurred in both tissue components in both regions, and the distribution pattern was quite different from that in adult females. The EGF level was increased by estrogen in adult but not in neonatal females. EGF-r and c-fos occurred in both uterine epithelium and stroma and in the vaginal epithelium; levels and distribution pattern were affected by estrogen. Neonatal estrogen treatment increased the levels of uterine EGF and c-fos in adult life. CONCLUSIONS: There are distinct developmental changes in the distribution and estrogen sensitivity of EGF. Only further studies can prove or disprove the association between the earlier reported disturbed growth control mechanisms in the uterus of adult but neonatally estrogen-treated females and the increased levels of uterine EGF and c-fos. The present results do not seem to explain mechanisms involved in the origin of neonatally estrogen-induced cervicovaginal epithelial abnormalities, nor do they explain the earlier described difference in estrogen-induced proliferative response between the uterine cervix and uterus proper.     

Infertility update: use of assisted reproductive technology

OBJECTIVE: To describe assisted reproductive technology (ART) and use of medications during these procedures. DATA SOURCES: Recent clinical literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: ARTs are procedures used in treatment of infertility that involve removal of oocytes and their manipulation outside the woman's uterus. The simplest form of ART, in vitro fertilization, involves aspirating eggs from the ovaries, fertilizing them outside the body, and transferring the embryos into the uterus at the four- to eight-cell stage. Experimental regimens for in vitro fertilization include use of various medications (gonadotropin-releasing hormone agonists, human menotropins, follicle-stimulating hormone, growth hormone) at varying points in the menstrual cycle and after introduction of the embryo into the uterus. Human chorionic gonadotropin has been used to increase implantation of embryos during the woman's luteal phase. Gamete intrafallopian transfer (GIFT) involves transfer of oocytes and sperm into the fallopian tubes, where fertilization takes place. This technique has the advantage of causing the zygote to enter the uterus at the time it would during natural conception. Zygote intrafallopian transfer is similar to GIFT, except that fertilization occurs in vitro, with embryos placed in the fallopian tubes at the two-cell stage. Various micromanipulation techniques and innovative sperm aspiration procedures are currently under development. CONCLUSION: Many advancements have been made in ART, and pharmacists who understand these procedures can serve patients by providing medication information in an empathetic and supportive manner.     

Postoperative suture manipulation for control of corneal graft astigmatism

Placenta percreta is a rare complication of pregnancy. Rupture of the uterus due to placenta percreta is one of the most urgent obstetrical catastrophes. Recently, we observed a patient who developed placenta percreta accompanied by spontaneous uterine rupture at 28 weeks of gestation. A 29-year old gravida 3, para 1, who had a history of one cesarean section and one miscarriage with dilatation and curetage, was seen at 28 weeks of gestation. An acute abdomen and shock were diagnosed. Immediate laparotomy revealed a transverse rupture on the fundus of the uterus. A hysterectomy was performed. Pathological examination of the uterus showed placenta percreta. Rupture of the uterus due to placenta percreta before the onset of labor is extremely rare.     

Abnormal twin pregnancy--early resorption of a single fetus in a twin pregnancy pregnancy]

INTRODUCTION: Twin pregnancy presents a condition of development of two fetuses in the uterus and can be monozygotic (single ovum) and dizygotic (two ova). In case of fertilization and segmentation of one ovum monozygotic twins are produced, while in case of fertilization of two ova, which can originate from one or two Graff follicles, dizygotic twins are developed. The ratio of twin and single pregnancies is 1:89 (according to Hellin's law) (1). The incidence of twin and other multiple pregnancies is influenced by: race of parents, age and parity of mother, use of clomid and gonadotrophin to stimulate ovulation, discontinued use of contraceptive pills and certain seasons (exposure to sunlight) (1). Due to occurrence of numerous complications twin pregnancy and parturition are considered to be highly risky. This is supported by clinical data on more frequent spontaneous abortions--especially in monozygotic pregnancies, hypertension in pregnancy, hemorrhage of various etiologies, anemias, early rupture of amniotic membranes, hydramnios, premature deliveries, etc. Nowadays diagnosis of both twin and other multiple pregnancies in the early stage is required, in order to establish normal or pathological development of such pregnancies. As early as 6 gestation week in twin pregnancies it is possible to sonographically visualize two gestation sacs in the uterus, while in 7-8 gestation weeks it is possible to see two embryos with evidence of fetal heart rate. In early pregnancy a differentially-diagnosed uterus may be clinically enlarged due to: hydratidaform mole, uterine mioma or ovarian cyst. In later gestation confirmation of twin pregnancy is possible by clinical and sonographic examination and biochemical analyses (elevated values of HPL and -fetoprotein) and less frequently, by x-ray. Repeated sonographic examinations can reveal the following anomalies of twin pregnancies: one normal pregnancy with one sac containing no embryo, one sac containing no embryo and one sac with a dead fetus, fetuses without vitality in both gestation sacs, two ultrasound echoes from which only one normal fetus and one dead mummified fetus (fetus papiraceus) result within the uterus. One gestation sac may be resorbed during pregnancy, while the undamaged fetus continues to develop normally in the uterus. In certain cases the loss of one fetus is not accompanied by any clinical symptoms, and in others this can be accompanied by light hemorrhage. An initial twin pregnancy after the loss of one twin may end by a birth of one healthy infant. CASE REPORT: A patient aged 35 years, came for gynecological examination due to missed menstruation. Ananmesis showed that she had a nascent uterine myoma which was removed by myomectomy six months earlier, had one parturition four years earlier, and no abortions. The last menstrual period was on February 12, 1991. Clinical examination showed a somewhat larger uterus than would be normal for amenorrhea of 9-gestation week. By sonographic examination two regular gestation sacs were found in the uterus with fetal echoes present as well as heart rate in both fetuses (Figure 1). Embryo measurements were as follows: Fetus 1-CRL-22.5 mm, NEG-8 + 4, heart rate present. Fetus 2-CRL-23.6 mm, NEG-9, heart rate present (Figure 2). The patient was cautiously informed that two fetuses are visible in the uterus and that this is a sign of twin pregnancy, but for certain diagnosis a control examination was scheduled two weeks later. The sonographic examination after 14 days later showed discord in fetal growth (Figure 3). Embryo measurement in 11-gestation week rendered the following parameters: Fetus 1-CRL-22.8 mm, NEG 8 + 6, no heart rate registered (Figure 4), while the second fetus continued to develop and had the following characteristics: Fetus 2-CRL-50.5 mm, NEG 11 + 4, heart rate and fetal movement registered (Figure 5). During entire pregnancy the patient suffered no pain or any kind of hemorrhage. She took no drugs. (ABST     

Detection of congenital müllerian duct anomalies using three-dimensional ultrasound

PURPOSE: The purpose of this study was to assess the value of 3-dimensional sonography in the diagnosis of congenital müllerian duct anomalies, which cause infertility, preterm labor, and first trimester abortion. METHODS: A prospective study was undertaken in which 40 patients with histories of repeated spontaneous abortions or infertility were first examined using conventional 2-dimensional sonography or hysterosalpingography. Three-dimensional transvaginal sonography was then performed. RESULTS: Twenty-eight women had müllerian duct abnormalities, and 12 women had normal uterine anatomy. Müllerian duct defects detected in this study were unicornuate uterus (3), bicornuate uterus (3), complete or partial septate uterus (12), arcuate uterus (9), and didelphic uterus (1). The diagnosis of müllerian duct anomalies in these patients was confirmed by laparoscopic and/or hysteroscopic examinations. Three-dimensional sonography demonstrated all congenital uterine abnormalities with a sensitivity and specificity of 100%. Separate uterus and bicornuate uterus could be correctly diagnosed using 3-dimensional sonography in 11 (92%) of 12 cases and 3 (100%) of 3 cases, respectively. These 2 abnormalities were commonly confused with each other using hysterosalpingography and conventional sonography. CONCLUSIONS: Three-dimensional sonography with image reconstruction is less expensive and less invasive than hysterosalpingography for the assessment of uterine anatomy and diagnosis of müllerian duct abnormalities. The ability to visualize both the uterine cavity and the myometrium on a 3-dimensional scan facilitates the diagnosis of uterine anomalies and enables the differentiation of septate from bicornuate uteri for preoperative surgical planning.     

An alternative approach to the surgical correction on malpositions of the uterus]

Endosurgical correction of the uterus was carried out in 57 patients. Indications for surgery were improper positions of the uterus-retroversio, retrodeviatio uteri, excessive mobility of the uterus, and complaints of heaviness at the bottom of the abdomen, leukorrhea, pain of different type in the lower portions of the abdomen, profuse and long menses, dyspareunic pain upon deep penetration, reduced libido, a sensation of a foreign body in the vaginal cleft, urine incontinence upon strain. The mean age of the patients was 35 +/- 3 years. The disease duration varied from 1 to 8-9 years. In 9 women endosurgical correction of the uterus was combined with other interventions on the pelvic organs: colpoperine-orrhaphy with levator plasty was carried out in 5, laparoscopic myomectomy in 2, and dissection of intraperitoneal adhesions in 2 patients. In addition, surgical sterilization was carried out in 54 patients. After surgery the patients were administered only nonnarcotic analgetics. All the patients were discharged on days 2-3, those subjected to combined treatment on days 8-9. The patients were followed up for up to 2 years. The general and psychoemotional status of the majority of patients improved, and the incidence of such symptoms as leukorrhea, pain at the bottom of the abdomen, profuse and long menses was 4, 6, and 5 times reduced, respectively. Endosurgical correction of the uterus in women of a reproductive age should be a method of choice; it can be carried out separately or in combination with plasty of the vaginal walls.     

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.     

Rapid prototyping for orthopaedic surgery

During pregnancy, mouse uterine epithelial cells produce and secrete a large amount of macrophage colony-stimulating factor (M-CSF/CSF-1). Macrophages accumulate and proliferate in the undecidualized endometrium of the pregnant uterus. Observations showed that macrophages expressed scavenger receptor class A (type I and type II) and class C (macrosialin). Scavenger receptors appeared to be involved in the removal of apoptotic cells in the degenerated decidual tissue. The expression of class A and class C scavenger receptor mRNAs in the uterus of pregnant mice was elevated but the expression of class B scavenger receptor (CD36) mRNA was similar to that of non-pregnant mice. The expression of various cytokines and chemokines, including M-CSF, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1-alpha), was enhanced in the uterus of pregnant mice, suggesting that these molecules regulate macrophage chemotaxis and immunological function in the uterus. These findings imply that the pregnant uterus provides a microenvironment for the recruitment, differentiation, and proliferation of macrophages and the regulation of scavenger receptor and cytokine expression for a successful pregnancy.     

The minimum dosage of praziquantel in the treatment of Taenia saginata, 1986-1993

Patients who have a unicornuate uterus with a noncommunicating rudimentary horn that contains an endometrial cavity are at risk for endometriosis and obstetric complications. As in this case, resection of the rudimentary horn can be performed laparoscopically without increased risk to the patient and with some potential benefit.     

Comparative study of the effects of clozapine and clothiapine in different preparations of guinea pig and rat isolated organs

1. A study has been made to know the effects of clozapine and clothiapine on the responses of rat isolated vas deferens to norepinephrine, dopamine and potassium, those of the rat isolated uterus to serotonin and potassium, and that of guinea pig isolated ileum to histamine. 2. Clozapine was a noncompetitive antagonist to norepinephrine, dopamine, serotonin and histamine; it inhibited potassium-induced contraction in isolated rat uterus and vas deferens. 3. Clothiapine was a competitive antagonist to serotonin and a noncompetitive antagonist to norepinephrine, dopamine and histamine; it inhibited potassium-induced contractions in isolated rat uterus and vas deferens.     

Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits

Oxygen tension was measured using flexible polarographic microelectrodes within the oviductal and uterine lumen in rhesus monkeys (n = 9), golden hamsters (n = 21) and rabbits (n = 6), during the reproductive cycle (monkey), during oestrus and pseudopregnancy (hamsters, rabbits) and during pregnancy (hamsters). In general, oxygen tensions in each species were much less than half of atmospheric O2, ranging from high values of about 60 mm Hg (8.7% O2) in the rabbit oviduct, rabbit and hamster uterus, to as low as 11 mm Hg (1.5% O2) in the monkey uterus. Oxygen tensions did not vary significantly between left and right sides of the reproductive tracts (all species), nor between pregnant and pseudopregnant states nor between oviduct and uterus (hamsters). Differences owing to reproductive stage were found in the monkey oviduct, hamster oviduct and uterus, and rabbit uterus. Oxygen tensions were consistently very low (11-14 mm Hg) in the monkey uterus throughout the menstrual cycle. In hamsters and rabbits, intrauterine O2 decreased significantly at about the normal time of blastocyst formation and implantation, to 37 mm Hg (5.3% O2) and 24 mm Hg (3.5% O2), respectively. This study indicates that embryos develop in vivo under low oxygen concentrations, especially during the peri-implantation period. The data have implications for investigations of embryo metabolism and for improving embryo development in vitro.     

Early diagnosis of uterine rupture after previous cesarean section]

A new diagnostic measure for the early detection of still uterus rupture before birth and previous cesarian section is reported. With a portio ready for birth, which permits the finger to pass readily, the possibility exists, after stripping of the membranes, to examine digitally the old caesarian scar in respect of a beginning or already existing scar dehiscence. In 112 investigated patients with this method, once a beginning, six times an incomplete and once a complete uterus rupture prior to another partus was seen. In six cases a stenosis was found in the old section region with retention of the foetal head and threatening uterus rupture.     

Monitoring intensive endurance training at moderate energetic demands using resting laboratory markers failed to recognize an early overtraining stage

Rupture of the gravid uterus remains one of the most disastrous complications of labour. Eighty cases of uterine rupture managed at Lagos University Teaching Hospital, Lagos over an eight year period were therefore reviewed to evaluate the characteristic of ruptured uterus in Lagos. The incidence of ruptured uterus was 5.01 per 1000 deliveries and unbooked patients accounted for 80%. Spontaneous rupture occurred in 73.8% while traumatic rupture was responsible for 26.3%. Diagnosis was not made in 25% of the cases until surgery. Poor antenatal care, foeto-pelvic disproportion, previous Caesarean section scar, grand-multiparity were major aetiological factors. Repair of the rupture with or without sterilization was carried out in 70% of the cases. Booking status and the type of surgical procedure did not significantly affect the maternal outcome. Ruptured uterus was responsible for 16.9% of the total maternal deaths in the period of review. The commonest cause of death in this series was hypovolaemic shock (64.3%). The overall perinatal mortality was 86.3% but the registered patients fared better. It was concluded that the incidence of ruptured uterus is still very high and probably on the increase in Lagos. Suggestions are made to improve the situation since the identified aetiological factors are largely preventable.     

Dexamethasone: increased weights and decreased [3H] estradiol retention of uterus, vagina and pituitary in the ovariectomized rat

Ovariectomized rats given 100 mug dexamethasone per day for 5 days had significantly heavier dry weights for uterus, vagina and pituitary, indicating a growth promoting activity of dexamethasone on these tissues in which estrogen normally promotes growth changes. The dexamethasone treated animals also retained significantly less [3H]estradiol per mug dry weight of tissue for uterus, vagina and pituitary. When[3H]estradiol retention was examined in vitro for the nuclear fraction, a significant decrease in retention was found for uterus, vagina and pituitary but not for hypothalamus or cerebral cortex. The decreased ability to bind [3H]estradiol, shown by the estrogen target tissues of the dexamethasone-treated rats, along with the increased growth of the estrogen target tissues, demonstrates that these tissues were able to show trophic responses even when greater levels were one-third of normal. Dexamethasone-treated animals tested for sexual receptivity in the presence or absence of progesterone priming did not show induction of facilitation of sexual receptivity. However, estrogen plus progesterone injections induced sexual receptivity in the presence of dexamethasone. When dexamethasone was combined with a dosage of estrogen, which by itself did not induce sexual receptivity, there was a significant response with 6 to 10 animals showing a low level of receptivity. Thus, dexamethasone can apparently synergize with estrogen to facilitate sexual receptivity.     

The effect of local chemical sympathectomy of the rat uterus on its sensitivity to sex hormones

Chemical sympathectomy of the rat uterus did not alter the main metabolic processes maintaining the uterus weight even though it changed its response to sex steroids. Sensitivity of endo- and myometrium to progesterone significantly decreased thus inducing a relative increase in the estradiol action.