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.     

Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract

The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350-353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.     

Embryo transfer--can we learn anything new from the observation of junctional zone contractions?

To assess whether embryo transfer can alter junctional zone contractility, we studied the effect of easy and difficult mock transfers in 14 oocyte donors during in-vitro fertilization (IVF) cycles. An Echovist bolus (30 microl) was used to represent embryos and transfer medium. An 'easy' transfer was judged to be an atraumatic insertion of the catheter without touching the uterine fundus. A 'difficult' embryo transfer was mimicked by deliberately touching the uterine fundus twice with the soft end of the cannula. Transvaginal scan images were recorded, digitized and converted into five times normal speed to allow us to evaluate junctional zone contractility. Easy mock embryo transfers did not change endometrial mechanical activity. Echovist remained in the upper part of the uterine cavity and was not dispersed after 45 min. A difficult procedure generated strong random waves in the fundal area and waves from fundus to cervix which relocated the Echovist in six out of seven cases. We observed movements of the transfer bolus from the upper part of the uterus towards the cervix (four cases) and into Fallopian tubes (two patients). Our study confirms that the mechanical activity of the uterus is capable of relocating intrauterine embryos and that this activity depends on physical stimulation. Junctional zone contractions can be implicated in cases of IVF/embryo transfer failure or ectopic gestation.     

Seminal transforming growth factor beta1 stimulates granulocyte-macrophage colony-stimulating factor production and inflammatory cell recruitment in the murine uterus

Mating in rodents evokes an inflammatory-like reaction within the uterine endometrium, characterized by extensive infiltration and activation of macrophages, dendritic cells, and granulocytes. This response is initiated when seminal vesicle gland-derived factors in the ejaculate stimulate uterine epithelial cells to release proinflammatory cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF). Experiments in which seminal vesicle secretions were fractionated by Sephacryl S-400 chromatography and assayed in vitro for GM-CSF-stimulating activity revealed that the seminal moiety coeluted with transforming growth factor beta1 (TGFbeta1) in the 150-440-kDa range and was neutralized by anti-TGFbeta1 antibodies. Comparable amounts of recombinant TGFbeta1 stimulated GM-CSF release in cultures of uterine epithelial cells from estrous mice and, when instilled into the uterine lumen, caused an increase in GM-CSF content and an infiltration of leukocytes into the endometrium similar to the postmating response. These results show that seminal vesicular fluid contains TGFbeta1 at levels sufficient to be the primary causative agent in the postmating inflammatory cascade through induction of GM-CSF synthesis by uterine epithelial cells. Seminal TGFbeta1 is thus implicated as a key factor in initiation of the remodeling events and immunological changes that occur in the uterus during the preimplantation period of pregnancy.     

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.     

Identification of specific relaxin-binding cells in the human female

Relaxin is secreted during pregnancy, but it has no verified effects in humans. The objective of the present study was to identify the cells containing specific relaxin-binding sites in the uterine cervix, vagina, uterus, mammary glands, mammary nipples, and term placenta in the human. The uterine cervix, vagina, and uterus were obtained from hysterectomy specimens. Mammary glands and nipples were obtained after modified radical mastectomy. Placenta was obtained after normal delivery. Tissue samples were cut into slices (0.5-3 cm3), frozen in liquid nitrogen, and cryosectioned (8 microm). Cells that bind relaxin were identified by sequential application of biotinylated porcine relaxin probe, antibiotin immunoglobulin G conjugated to 1 nm colloidal gold, and silver enhancement for signal amplification. Relaxin bound with specificity to epithelial cells, smooth muscle cells, and blood vessels in the cervix, vagina, uterus, and mammary nipples; to epithelial cells and blood vessels in the mammary glands; and to skin of the mammary nipples. In addition, relaxin bound to individual cell types within the term placenta (amnion epithelium, syncytiotrophoblasts, blood vessels), and to sebaceous glands within the nipples. We conclude that the specific relaxin-binding cells probably contain relaxin receptors. Identification of putative relaxin receptors may provide insight into physiological and/or therapeutic roles of relaxin in the human.     

The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract

The xenoestrogen bisphenol A (BPA) has been shown to mimic estrogen both in vivo and in vitro. BPA stimulates PRL secretion and the expression of a PRL regulating factor from the posterior pituitary in the estrogen-sensitive Fischer 344 rat (F344), but not in Sprague-Dawley (SD) rats. The goal of the present studies was to examine the in vivo actions of BPA on the reproductive tract. The specific objectives were 1) to characterize the short term effects of BPA on cell proliferation and c-fos expression in the uterus and vagina, and 2) to compare the effects of prolonged exposure to low doses of BPA on the reproductive tract of F344 and SD rats. Treatment with single high doses of BPA induced cell proliferation in the uterus and vagina of ovariectomized F344 rats, as determined by bromodeoxyuridine immunostaining. This proliferation was dose dependent (from 37.5-150 mg/kg) and followed a time course similar to that of estradiol (E2). Quantitative RT-PCR revealed that both BPA and E2 increased c-fos messenger RNA levels in the uterus 14- to 16-fold within 2 h, which returned to basal levels after 6 h. In the vagina, BPA-induced c-fos expression remained elevated for up to 6 h, compared with the transient increase caused by E2. Treatment of F344 rats for 3 days with continuous release capsules that supplied a much lower dose of BPA (approximately 0.3 mg/kg x day) resulted in hypertrophy, hyperplasia, and mucus secretion in the uterus and hyperplasia and cornification of the vaginal epithelium. The reproductive tract of SD rats did not respond to this treatment paradigm with BPA. These studies demonstrate that 1) the molecular and morphological alterations induced by BPA in the uterus and vagina are nearly identical to those induced by estradiol; 2) the vagina appears to be especially sensitive to the estrogenic actions of BPA; 3) the reproductive tract of the inbred F344 rat appears more sensitive to BPA than that of the outbred SD rat; and 4) continuous exposure to microgram levels of BPA is sufficient for exerting estrogenic actions.     

Preoperative sonographic measurement of endometrial pattern predicts outcome of surgical repair in patients with severe Asherman's syndrome

OBJECTIVE: To assess the predictive value of preoperative endometrial sonography in the diagnosis and surgical treatment of women with amenorrhea due to severe Asherman's syndrome. DESIGN: Patient series. SETTING: Academic clinical practice. PATIENTS: Seven women with severe Asherman's syndrome characterized by amenorrhea despite normal ovulatory function and complete obstruction of the uterine cavity at the level of the cervix or lower uterine segment at hysterosalpingogram. MAIN OUTCOME: Ability of vaginal sonography to predict successful hysteroscopic treatment as assessed by resumption of menstrual cyclicity and normalization of the uterine cavity. RESULTS: Transvaginal sonography demonstrated a well-developed endometrial stripe in three of seven women, while three others had virtually no endometrium seen. All women with well-developed endometrium were found to have adhesions occluding the lower uterine segment and had resumption of normal menses and normalization of the cavity after hysteroscopy. The women with minimal endometrium had no cavity identified and derived no benefit from surgery. A seventh woman with endometrium seen only on one side of the cavity had patency successfully established only on that side. CONCLUSION: The endometrial pattern seen with transvaginal sonography is highly predictive of surgical and clinical outcome in women with severe Asherman's syndrome characterized by complete obstruction of the cavity at hysterosalpingogram.     

Thrombosis following hip arthroplasty. A study using phlebography and 125I-fibrinogen test

The rate of incidence and morphology of metastases in 284 Fallopian tubes from 148 patients with primary uterine corpus cancer have been investigated. In 44 patients metastases were discovered in inner organs, of which in 17 (11.5% patients) in 23 oviducts. In 10 of these patients the Fallopian tubes were the only localization of metastases. Macroscopical alterations in the form of thickening and condensation, tumor nodules on the surface of the affected oviducts were discovered in 7 cases. In the remainder no macroscopical changes have been noted. There predominated lymphogenic metastases, in a smaller number of cases there were implantation and lymphogeno-implantation type metastases, localized mostly in the ampullary regions of the oviducts. More often, one could observe involvement by lymphogenic metastases of the subserosal layers together with muscular tissue, less frequently of mucosal layers, and total involvement of all layers of the wall of Fallopian tubes in the form of single or multicentric tumor nests, or diffuse tumor infiltration of tissues of the oviduct wall. Implantation metastases in the form of micronodules, multicellular agglomerates were discovered on the serosa more often than on the mucosa of Fallopian tubes. Secondary oviduct carcinomas differ from primary ones by their histological structure and character of growth. The Fallopian tubes play an essential role in the dissemination of metastases in the presence of primary uterine corpus carcinoma.     

Involvement of the pelvic plexus and the suprarenal ganglia in the neuropeptide Y (NPY) innervation of the cervix and the uterus of the rat

The involvement of the pelvic plexus and suprarenal ganglia in the neuropeptide Y (NPY) innervation of the genital tract was studied in the female rat by means of denervation experiments and retrograde tracing studies. Removal of the paracervical ganglia caused a significant decrease of the NPY-immunoreactive nerve density and NPY concentration in the lower part of the genital tract: cervix, uterine body and lower part of the uterine horn. The decrease in NPY concentration in these three regions was more pronounced after lesion of the pelvic plexus. Lesion of the ovarian nerve plexus caused a depletion in the NPY-immunoreactive nerve fibres and a decrease in NPY concentration in the upper part of the uterine horn. Pelvic nerve section, inferior mesenteric ganglia excision and superior ovarian nerve section had no effect on the NPY innervation in the genital tract. Injection of fluorogold into the cervix and lower part of the uterus combined with immunohistochemistry revealed that 87.5% of labelled neurons in the pelvic plexus were NPY-immunoreactive. Following injection of fluorogold into the upper part of the uterus, 92% of labelled neurons in the suprarenal ganglia were NPY-immunoreactive. Treatment with 6-hydroxydopamine revealed that the NPY-immunoreactive nerve fibres were non-noradrenergic in the cervix, but were noradrenergic in the upper part of the uterus. In the uterine body and lower part of the uterine horn, both noradrenergic and non-noradrenergic NPY-immunoreactive nerve fibres were observed. These data demonstrate the major contribution of pelvic plexus neurons in the non-noradrenergic NPY innervation of the lower part of the genital tract, and the involvement of the suprarenal ganglia in the noradrenergic NPY innervation of the upper part of the uterus via the ovarian nerve plexus.     

Ineffectiveness of heparin treatment in burn shock in the guinea pig

Homogenates of tissue from the female genital tract contain isoamylases which are, to a certain extent, electrophoretically distinguishable from the pancreatic and salivary isoamylases. In healthy nonpregnant women, high levels of activity of genital isoamylases were found in tissue homogenates of cervical and Fallopian tube mucosa, whereas activity was weak or absent in homogenates of endometrium. The isoamylases of the cervical mucosa had an electrophoretic migration rate toward the anode identical to that of the salivary main fraction, whereas the isoamylases of the Fallopian tube migrated faster. Specific genital isoamylase activities were also demonstrable in peritoneal fluid collected from the cul-de-sac. During the menstrual cycle, these activities showed a midcycle peak. In pregnant women, the levels of activity of the genital isoamylases in peritoneal fluid were lower than in nonpregnant women. In homogenates of the male accessory genital glands, the isoamylases specific for the genital tract were present in minute amounts. The isoamylases specific for the genital tract were not detectable in serum in either sex.     

A case of unique communication between blind-ending ectopic ureter and ipsilateral hemi-hematocolpometra in uterus didelphys

Uterus didelphys with double vagina and hemi-vaginal atresia is a rare syndrome of congenital anomalies. A 17-year-old girl had a right blind-ending ectopic ureter, the proximal end of which communicated with the ipsilateral uterine cervix of uterus didelphys. The patient presented with vaginal urinary incontinence after incision of the vaginal wall for right hemi-hematocolpometra. Following various examinations, the ipsilateral kidney was found to be absent. The ectopic ureter and communicating duct were resected, and the fistula was closed. The genesis of malformation of the female genitalia and urinary tract resulting in such a unique communication is discussed. The importance of preoperative meticulous examinations, including cysto-genitography, pelvic magnetic resonance imaging and panendoscopy with the patient under anesthesia, is emphasized.     

The effect of ovarian steroids on epithelial ciliary beat frequency in the human Fallopian tube

Using a method that detects variations in light intensity we have studied the effect of ovarian steroids on human Fallopian tube epithelial ciliary beat frequency in vitro. We have found that baseline ciliary beat frequency averages between 5-6 Hz. Cilia from ampullary segments of the Fallopian tube beat significantly faster (5.4 Hz+/-0.2) than those from fimbrial segments (4.8 Hz+/-0.2). There was no significant difference in baseline ciliary beat frequency at any other anatomical site in the Fallopian tube. Incubation with progesterone (10 micromol/l) suppresses human Fallopian tube epithelial ciliary beat frequency by 40-50%. This inhibition was observed at similar magnitudes in all Fallopian tubes studied irrespective of anatomical site. Progesterone-induced reductions in ciliary beat frequency were concentration dependent and prevented by the progesterone receptor antagonist mifepristone (RU486). Oestradiol alone (10 micromol/l) had no effect on ciliary beat frequency at any anatomical site in the Fallopian tube but did prevent the reduction in ciliary beat frequency seen with progesterone when tissues were incubated with these two steroids together.     

PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus

We have used a combination of computerized database mining and experimental expression analyses to identify a gene that is preferentially expressed in normal male and female reproductive tissues, prostate, testis, fallopian tube, uterus, and placenta, as well as in prostate cancer, testicular cancer, and uterine cancer. This gene is located on the human X chromosome, and it is homologous to a family of genes encoding GAGE-like proteins. GAGE proteins are expressed in a variety of tumors and in testis. We designate the novel gene PAGE-1 because the expression pattern in the Cancer Genome Anatomy Project libraries indicates that it is predominantly expressed in normal and neoplastic prostate. Further database analysis indicates the presence of other genes with high homology to PAGE-1, which were found in cDNA libraries derived from testis, pooled libraries (with testis), and in a germ cell tumor library. The expression of PAGE-1 in normal and malignant prostate, testicular, and uterine tissues makes it a possible target for the diagnosis and possibly for the vaccine-based therapy of neoplasms of prostate, testis, and uterus.     

Colposcopy images of cervix in women with Gardnerella vaginalis infection

Among micro-organisms infecting vagina whose dominant genus is GV anaerobic bacteria are often present. There are reports that GV infections of vagina and uterine cervix, apart from their well-known negative role in obstetrics practice can play a role in carcinogenic processes of uterine cervix. The aim of the study was to assess characteristic colposcopy images of cervix in women with Gardnerella vaginalis infection. The research was carried out on 1180 women hospitalised in the period of 14 months. Many observations lead to conclusions that pathognomic clinic feature of Gardnerella vaginalis infection of uterine cervix is visible in colposcope presence of clean, translucent mucus in external cervical os and opaque vaginal contents in the rear vaginal vault. High hydrogen ion concentration in vaginal contents (pH 6.0 and over) correlates with positive "fishy odour test" of this contents. Gardnerella vaginalis infection of vagina and uterine cervix concerns women with existing erosion-type changes of uterine cervix. Visible in colposcopic test restless and "spotted" images visible after Schiller test are pathognomic colposcopic features of Gardnerella vaginalis infection.     

Characterization of nitric oxide synthase activity in rabbit uterus and vagina: downregulation by estrogen

Nitric oxide synthase (NOS) was determined in the soluble (cytosolic) and particulate fractions of rabbit uterus, vagina and cerebellum and the influence of estrogen treatment on NOS activity was studied. NOS in both the cytosolic and particulate fractions was highly calcium dependent. The activity in cytosolic fraction was nearly 4-fold higher than the particulate fractions from all three organs. The concentration of NOS was highest in cerebellum followed by vagina and uterus. Vaginal NOS activity was 3-4-fold higher than the uterine NOS. After a continuous treatment of rabbits for one week with estrogen, cytosolic NOS was reduced by nearly 7 and 4-fold in the uterus and vagina, respectively, whereas there was no significant change in the particulate NOS. Estrogen treatment caused no change in cytosolic or particulate NOS from the cerebellum. Downregulation of cytosolic NOS by estrogen in the estrogen target tissues like uterus and vagina and absence of effect in the cerebellum strongly suggests a physiological significance.     

Immune aspects of endometriosis: relevance of the uterine mucosal immune system

Endometriosis is classically defined as the growth of endometrial cells at sites outside the uterus. It is a common disease characterized by infertility, chronic pain and adhesion formation. Immune dysregulation, evidenced by decreased clearance of endometrial cells and aberrant production of cytokines by peritoneal fluid leukocytes, has been proposed as a mechanism which allows implantation and growth of ectopic endometrium. Cytokines are primary components of intercellular signaling between uterine epithelial and stromal cells, leukocytes, and the developing conceptus. Because their production is regulated by sex hormones, cytokines are well-placed to play a key role in the extensive tissue remodeling required to accommodate menstruation, implantation and pregnancy. Understanding this specialized hormonally-responsive mucosal immune system within the uterus will be critical to understanding the potential importance of the immune system in the pathogenesis of endometriosis. In this review, highlights of studies describing leukocyte populations, cytokines and cytokine receptors in uterine and ectopic endometrium and their proposed role in the regulation of immune processes and endometrial growth are presented, followed by a review of current data on immune aspects of endometriosis. Studies directed at investigating the hormonal regulation of cytokine secretion by uterine and peritoneal cell populations, and the effect of cytokines on endometrial proliferation, should provide a more complete understanding of their potential role in normal uterine growth and in the pathogenesis of endometriosis.     

Dual-mode presentation and its effect on implicit and explicit memory

Chronic exposure to methyl tertiary butyl ether (MTBE) altered the rodent tumor incidence of endocrine-sensitive tissues and decreased the incidence of estrogen-dependent uterine cystic hyperplasia in mice. To test the hypothesis that changes in the incidence of tumors in female B6C3F1 mice after MTBE exposure are secondary to endocrine alterations, we exposed female mice to the carcinogenic dose of MTBE vapor (8000 ppm) for 3 or 21 days or 4 or 8 months under conditions similar to a previous 2-year bioassay. MTBE exposure significantly decreased body weight gain and ovary and pituitary weight at 4 and 8 months and uterine weight at all time points. After 8 months of exposure, MTBE significantly increased the length of the estrous cycle by increasing the mean number of days in both the estrus and the nonestrus stages. Histological evaluation of H&E-stained tissues showed a decrease in the number of uterine glands after subchronic MTBE exposure. DNA synthesis, as measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU), was decreased in uterine glandular and luminal epithelial cells after MTBE exposure for 3 or 21 days or 4 or 8 months. MTBE exposure decreased the number of epithelial layers in the cervix and vagina at all time points. DNA synthesis was decreased in cervical and vaginal epithelium after 21 days of MTBE. Decreased zona reticularis of adrenal glands was found after 4 and 8 months of MTBE exposure without changes in BrdU incorporation. MTBE did not competitively bind to estrogen receptor. MTBE exposure did not alter serum estrogen levels or alter the location or intensity of estrogen receptor immunoreactivity in the uterus, cervix, and vagina. These data indicate that while MTBE exposure causes multiple endocrine-related tissue and cellular responses, these effects are not mediated through the estrogen receptor.     

Immunocytochemical localization of progesterone receptor in the reproductive tract of adult female rats

The distribution of the progesterone receptor (PR) was investigated immunocytochemically in female reproductive tracts of rats during the estrous cycle and early pregnancy through use of an anti-PR monoclonal antibody. PR was localized predominantly in the nuclei of epithelial, stromal, and muscle cells in the uterus and vagina during the estrous cycle. In the uterus, the nuclei of epithelial cells were stained intensively at diestrus, while the PR staining of the stromal cells was more intense at proestrus than at any other stage of the cycle. PR expression during the cycle in muscle cells of the myometrium was similar to that in the endometrial stromal cells. In the vagina, however, PR expression during the cycle was approximately the same among epithelial, stromal, and muscle cells, the nuclei of which were stained deeply at proestrus. Ovariectomy at various stages of the cycle altered the PR expression appearing in the uterus and vagina during the cycle. In ovariectomized rats, estrogen increased the PR immunoreaction of various types of cells examined in the uterus and vagina except for the uterine epithelial cells. The reaction of these uterine epithelial cells was decreased by estrogen but was increased by progesterone given after estrogen; however, progesterone given alone reduced the reaction. In the epithelial and stromal cells of the uterus, intensity of the staining was increased after mating, reaching maximum on Day 3 of pregnancy, and then decreased on Day 4 (day of implantation), while in epithelial and stromal cells of the vagina the staining remained weak during early pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)