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The estrogen-dominated baboon oviductal epithelium synthesizes and secretes a family of oviduct-specific glycoproteins. The objective of this study was to determine if these glycoproteins become associated with ova and early embryos. Ovarian and oviductal eggs obtained from superovulated baboons 72 h post-hCG were subjected to an indirect immunofluorescent assay that used a polyclonal antibody prepared toward the baboon oviduct-specific glycoproteins. Oviductal ova as well as 2-cell and 4-cell embryos showed intense, specific fluorescence within their zonae pellucidae. Ovarian ova did not exhibit fluorescence. Oviductal eggs were also fixed and processed for peroxidase-antiperoxidase immunocytochemistry and colloidal gold immunoelectron microscopy to confirm the immunofluorescent data and to determine the subcellular distribution of the antigens. Oviductal ova as well as 2-cell and 3-cell embryos exhibited immunolabeling localized within the zona. Gold particles were distributed uniformly throughout the width of the zona. Occasional groupings of gold particles were observed within the zona. Also, in most eggs, immunoreactivity was observed associated with flocculent material in the perivitelline space as well as the vitelline membrane. Furthermore, immunogold labeling above background level was noted in the cytoplasm of the eggs, particularly in the blastomeres of 3-cell embryos. Collectively, these results indicate that baboon estrogen-dependent oviductal secretory glycoproteins become intimately associated with oviductal ova and with embryos.

We have previously demonstrated that pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the human glycosylated beta-lactoglobulin homologue (HG-BLG), is quantitatively the major secretory soluble protein product of the secretory endometrium during the latter half of the menstrual cycle and decidua spongiosa of the gestational endometrium during early pregnancy, and is principally localized to the glandular epithelium. In the present study employing monoclonal antibodies in immunohistological techniques, the distribution and localization has been examined in normal and pathological tissues of the adult and first-trimester fetus. No significant staining for alpha 2-PEG was detected in any nonreproduction-associated tissue in the normal adult nor any tissue in the fetus. In the adult, most intense staining was associated with the endometrial glandular epithelium in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle and pregnancy, appearance of alpha 2-PEG in endometriosis was strongly linked with its appearance in uterine endometrial tissue, suggesting that endometriotic tissue exhibited competence to respond to the same hormonal milieu required to induce synthesis in the uterine endometrium. Localization to the mucosal epithelium of the Fallopian tube was consistent with synthesis of alpha 2-PEG, albeit at low levels, and staining at this site reflected fluctuations of staining within the uterus. Of the pathological specimens examined, staining was only detected in a proportion of ovarian carcinomas. No staining was detected in the mammary gland, a site of beta-lactoglobulin synthesis, whether obtained during pregnancy or lactation.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously shown that pregnancy-associated alpha 1-globulin, a small molecular weight (32 kDa) insulin-like growth factor-binding protein (IGF-BP), is quantitatively the major secretory protein product of the decidualized endometrium during human pregnancy and is localized principally in the decidual cell. In the present study, employing monoclonal antibodies in immunohistological techniques, the distribution and localization of IGF-BP has been examined in normal and pathological tissues of the adult and first trimester fetus. In the adult, most intense reactivity was associated with endometrial stroma and their derived decidual cells in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle, the appearance of IGF-BP in endometriotic tissue was linked with its appearance in uterine endometrial tissue. The only other adult cells where significant staining was detected was in the luteal cells of the corpus luteum. Production of the protein was not a feature of carcinomas. In the fetus, the protein was localized in lymphoid-myeloid progenitor cells and hepatocytes of the liver and at lower levels in testicular Leydig cells and adenocortical cells. These observations suggest highly specific tissue expression of this protein and support a specialized role for this protein in progenitor cells of the lymphomyeloid system, in certain steroid hormone-producing cells and in the decidual cell in pregnancy.

Oviducts were obtained from a series of cycling and ovariectomized steroid-treated baboons. The lining epithelium of the ampulla and isthmus was analyzed by light and electron microscopy. Both morphological and cytomorphometric analyses revealed that the morphological and functional state of the oviductal epithelium in the baboon is controlled by the ovarian steroids. Additionally, a clear cephalocaudal steroid-responsive gradient was observed when the data from the ampulla and isthmus of the same animal were compared. Within the ampulla, estradiol induced hypertrophy, hyperplasia, ciliogenesis, and secretory activity, whereas adding progesterone to the treatment regimen (+/- estradiol) resulted in atrophy, deciliation, apoptosis, and loss of the secretory activity. These cyclic processes were less evident in the isthmus. We also used an indirect electron microscopic immunogold technique and a previously characterized polyclonal antibody to determine the localization of oviduct-specific glycoproteins. These glycoproteins were present in every secretory granule observed, regardless of oviduct region, electron density, or size of the secretory granule. In summary, our data show that 1) estradiol induces and maintains the mature epithelium of the baboon oviduct, 2) steroid withdrawal or the administration of progesterone causes regression of the epithelium, and 3) the previously identified estradiol-dependent oviduct-specific glycoproteins are synthesized within and released from the secretory epithelial cells.

With the aid of monoclonal antibodies specific to the estrogen and progestin receptors, we have examined the cellular localization of these proteins in the reproductive tract of male and female macaques. Two striking findings have resulted from our work with these new reagents. First, these receptors are detectable only in cell nuclei, regardless of hormonal treatment, and second, they are often detectable in stromal, but not epithelial cells when the epithelial cells undergo various estrogen or progestin-dependent events. The latter observation has led us to conclude that stromal cell-epithelial cell interactions may play previously unappreciated roles in the hormonal control of the primate reproductive tract. The lines of evidence that have drawn us to this conclusion will be reviewed.

Glycogen in the ciliated cells of the epithelium of the Fallopian tube of Capra hircus, undergoes no variation during the different phases of the reproductive cycle. The nonciliated secretory cells show glycogen, neutral, sialo- and sulfomucins during the estrous period, the intensity of reaction being less in the isthmus region. During early pregnancy there is an overall decrease in the mucins content. Sulfomucins are absent from the infundibular region and acid mucins are not observed in the isthmus during early pregnancy.

The uptake and retention of a radiolabeled synthetic progestin, ORG 2058, was studied in the female reproductive system of the baboon. Four estrogen-primed baboons were injected intravenously with 2.5 micrograms/kg body weight of 3H-ORG 2058. One animal, which served as a control, received an additional injection of 2.5 mg/kg body weight of unlabeled progesterone. One hour after the injections, the animals were killed and the uterus, cervix, oviduct, vagina, and labia were removed and processed for autoradiography. The cells in the germinative layers of the stratified squamous epithelium of the cervix, vagina, and labia demonstrated nuclear localization of the label. The columnar epithelium, both surface and glandular, of the uterus and cervix sequestered the synthetic steroid; however, the nuclei of the epithelium lining the oviduct were unlabeled. The nuclei of the fibroblasts and of the smooth muscle cells were labeled in all the organs studied. These preliminary observations suggest that there is a stage in the reproductive cycle in which progesterone receptors are contained in the stromal cells of the oviduct but are absent in the epithelium.

The content of catecholamines in the Fallopian tube and the uterus and the plasma levels of estradiol and progesterone were studied in cycling women. During the follicular phase norepinephrine levels were 33.4+/-7.1, 50.5+/-8.0, and 145.7+/-43.6 ng. per gram of wet tissue in the external, middle, and internal segments of the Fallopian tube, respectively. During the luteal phase norepinephrine content increased significantly in the external and middle portions (219.3+/-57.0 and 206.2+/-34.3 ng. per gram) whereas it remained unchanged in the internal one (185.2+/-53.6 ng. per gram). The NE content of the external and middle segments correlated significantly with plasma progesterone levels (r = 0.76 and 0.82, respectively, whereas oviductal epincphrine levels did not show significant changes as a function of the stage of the menstrual cycle. Uterine epinephrine content decreased by 67 per cent during the luteal phase whereas norepinephrine remained unchanged.

Pyruvate and lactate were measured in oviducts during the first 5 days following ovulation in cycling, pregnant, and pseudopregnant mice, to determine how oviductal metabolism might change to promote the availability of these substrates to the early embryo. The postovulatory peak in ampullar pyruvate was most evident in the 12-h pregnant oviduct, 3.19 mmol . kg-1. This increase at +12 h was related to a decrease in lactate dehydrogenase (LDH) activity, compared to cycling animals, observed at this time. Although cycling animals showed a significant increase in isthmic pyruvate at +3 h, no change in isthmic pyruvate was observed in either mated group through the postovulatory period. Isthmic LDH activity was also unchanged in cycling or mated animals through this period. Ampullar lactate in both mated groups was elevated at 12 to 24 h after ovulation, a pattern similar to that seen in cycling animals. Isthmic lactate levels also increased after ovulation in all groups, but in the pregnant group the lactate remained elevated (25-28 mmol . kg-1) through 72 h, while concentrations in the cycling and pseudopregnant animals, returned to low levels (14-16 mmol . kg-1) by 48 h. The patterns of pyruvate and lactate, especially those in the pregnant animals, seem suited to providing these metabolites at levels near those required for optimal in vitro embryo growth. The +12 h ampullar pyruvate peak noted in mated animals implies a specific response to the mating stimulus. Prolongation of increased isthmic lactate levels only in pregnant animals suggests a response of the oviduct to the viable embryo.

The concentrations of tinidazole in various tissues and body fluids were studied in gynaecological patients after a single 2g oral dose. Tinidazole was determined by the agar-diffusion technique using a strain of Clostridium bifermentans. Reliable estimates of concentrations down to 0.5 microng/ml could be obtained. Dichloromethane extraction of tinidazole added to various tissues in known amounts gave a recovery of 100 +/- 10%. Peak serum values of 32-52 microng/ml were reached 3-6h after the administration. The concentrations in peritoneal fluid, obtained at operation 8.5-15h after the intake, varied between 16 and 40 microng/ml. Specimens from the Fallopian tubes yielded 15-26 microng tinidazole/g tissue; similar levels were obtained specimens from myometrium, endometrium, portio, vaginal secretions, omental fat, and cutis. It is concluded that, with the given dose, tinidazole concentrations are achieved in fluids and tissues of the female genital tract that are far in excess of those that should be therapeutical in infections caused by microorganisms know to respond to nitroimidazole treatment.

The occurrence and the localization of 4-aminobutyrate:2-oxoglutarate transaminase (GABA-transaminase) in the non-pregnant and pregnant rat oviduct were examined using biochemical and enzyme histochemical techniques. Specific GABA-transaminase activity was detected in the ampullary and isthmic portions of the oviduct as well as in the utero-tubal junction. The enzymic activity was lower in the ampullary than in the isthmic or intramural segments of the oviduct. Pregnancy induced a significant increase of GABA-transaminase activity in each portion of the oviduct. Enzyme histochemistry showed the highest GABA-transaminase reactivity at the level of the epithelial cells of the oviduct irrespective of the portion of the tube examined. A faint specific activity was demonstrated in the smooth muscle of the oviduct while the serosa did not show specific staining. Our findings indicate that: the observed increase of GABA-transaminase activity in the oviduct of the pregnant rat may be responsible for the reduced GABA levels in the oviduct during gestation; and the extraneuronal localization of GABA-transaminase activity does not seem to support the suggestion of a possible GABAergic innervation of the oviduct.

We studied the pathway of serum protein transport into the lumen of the mouse oviduct by localizing several tracer proteins in the oviduct after intravenous injection on days 1, 5, and 11 of pregnancy. Fluorescent proteins were observed in the lamina propria and in vesicles in the lumenal epithelial cells mainly in the preampulla segment on days 5 and 11 of pregnancy. In the isthmus, there was much less fluorescence in the lamina propria and no fluorescent vesicles in lumenal epithelial cells. This is similar to previous observations on day 1 and indicates that the uptake of serum proteins into lumenal epithelial cells in the preampulla is not limited to the time when embryos are present in the oviductal lumen. Horseradish peroxidase (HRP) was present in the lamina propria of the preampulla on days 1 and 5, but direct tracer movement into the oviductal lumen was blocked by the epithelial junctional complexes. Within the epithelial cells, HRP was localized in endocytic vesicles along the basolateral membrane, multivesicular bodies (mvb), elongated dense bodies below the nucleus (bdb), and many small vesicles near the apical surface of the cells. Ferritin was also used as a tracer and was observed in the same locations as HRP. Acid phosphatase in the epithelial cells of the preampulla on day 1 was localized in mvb and bdb, indicating that these structures are lysosomes. It appeared that HRP and ferritin followed two pathways after basolateral endocytosis by the epithelial cells in the preampulla: 1) they were transported to apical vesicles that may release their contents into the oviductal lumen, or 2) they were transported to lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the temporal relationships between ovum transport and changes in the concentration of nuclear steroid receptors in the oviduct of cyclic and pregnant rats. A lack of parallelism between estrogen and progesterone fluctuations in plasma and their respective nuclear receptor concentrations in the oviduct predominated during egg transport. In pregnant animals, oviductal egg transport took 24 h longer than in nonpregnant animals. In both conditions, transport was initiated while the action of estrogen and progesterone on the oviduct--measured as nuclear receptor accumulation--was decreasing. Three or four days later, depending on whether the animal was pregnant, the eggs entered the uterus shortly after an increase in the nuclear receptor accumulation of both hormones. Treatment with RU486, a progesterone receptor-blocking agent known to cause premature arrival of eggs in the uterus, advanced estrogen receptor accumulation in the oviduct of pregnant rats. These data suggest that the arrival of eggs in the uterus is timed by a transitory increase in nuclear estrogen receptor in the oviduct that does not necessarily reflect a similar change of circulating estradiol. Moreover, in pregnant rats, the onset of this estrogenic action is delayed by a progesterone receptor-mediated effect that hinders nuclear estrogen receptor accumulation.

Catecholamines were measured in various regions of the human Fallopian tube at different cyclic stage with high performance liquid chromatography; these stages were defined from plasma estradiol and progesterone levels. The tube contained minute amounts of epinephrine, low concentration of dopamine, and approximately 250-800 ng/g of norepinephrine. Measurements of norepinephrine in consecutive sections along the organ showed clear regional variations. The highest concentration was found in the isthmus. There was a consistently higher norepinephrine concentration during the luteal compared to the follicular phase. The highest norepinephrine values in the isthmus and in the fimbriated end were found at the time of ovulation.

Diffusion of aztreonam into female genital tract tissues was investigated. After a single IV injection of 1 g, aztreonam was assayed in uterine tissue, uterine tube tissue and peritoneal fluid in 15 patients undergoing coelioscopy or hysterectomy. In addition, to evaluate placental transfer of aztreonam, maternal blood, amniotic fluid and cord blood samples were collected in five women undergoing cesarean section. Concentrations of aztreonam were determined using a microbiologic method. Mean concentrations 1 to 2 hours after administration of the drug were 11 to 25 micrograms/g in the endometrium and uterine tube tissue and 18 to 30 micrograms/g in the myometrium. Concentrations in peritoneal fluid samples were lower, ranging from 4.7 micrograms/ml (0.5 h) to 16 micrograms/ml (1 to 2 hours after the injection). The ratio of tissue concentrations to serum concentrations found at the same time, expressed as a percentage, ranged from 50 to greater than or equal 100%. Placental transfer of aztreonam proved comparable to that of other recently studied beta-lactams: the amniotic fluid/maternal blood and cord blood/maternal blood ratios ranged from 27 to 33% thirty minutes after administration of the antibiotic. No adverse effects were recorded in the offspring. These results indicate that diffusion of aztreonam into female genital tract tissues is good, producing concentrations capable of preventing or curing gynecologic and obstetrical infections caused by Gram negative bacilli.

Spontaneous electromyographic (EMG) activity of the oviduct recorded in vivo in untreated, estrogen-treated, and progesterone-treated castrated rabbits was found to exhibit two main patterns: short spike bursts lasting 1-10 s and long trains of action potentials lasting several minutes, which constituted the major component of EMG activity. After estrogen treatment, both wet weight and noradrenaline (NA) content of the castrated rabbit oviduct were enhanced mainly at the ampullary-isthmic junction; long trains of discharges were significantly shorter (2.0-2.7 min vs 3.6-4.6 min) and appeared at more frequent intervals (9.8-12.2 min vs 14.2-22.6 min). After progesterone treatment, spontaneous EMG activity was not significantly different from that in untreated castrated rabbits (as was the NA content) except at the ampullary-isthmic junction. NA injection elicited a stimulatory response of the oviduct lasting 1-7 min in the three hormonal states. Phentolamine strongly depressed spontaneous EMG activity but the inhibition was more transient in castrated rabbits than in estrogen-treated and progesterone-treated animals. Propranolol had no effect on spontaneous EMG activity. These data and the high NA concentrations found in all parts of the isthmus support the hypothesis that adrenergic innervation plays a role in the organization of oviductal motility in the rabbit.

An enzymatic microassay method for glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) was improved to yield a high sensitivity and a low blank. The 20-microns thick freeze-dried sections (0.2-1.5 micrograms dry weight) were prepared from the oviduct and ovary of rat. The analysis of these microsamples by the improved method showed that, contrary to the previous observations, the rat ovary is devoid of GAD activity and contains a trace amount of GABA. Both are present abundantly in the oviduct. In the oviduct mucosa, significant GAD activity was found in the estrous phase, whereas the activity was nearly null during other phases of the estrous cycle. GABA concentration in the oviduct mucosa was 10-fold higher than in the cerebral cortex; its variation during the estrous cycle was not remarkable. In the muscle layer of oviduct, GAD activity had a low peak in the estrous phase and GABA concentration was almost constant during the estrous cycle. The denervation experiment showed that GAD is present in the nerve terminals innervating the oviduct.

The content of 17 beta-estradiol in cytosol of guinea pig and human estrogen-sensitive tissues was determined by radioimmunoassay. The evaluation of accuracy and precision of the obtained data confirms reliability of the assay. The present study has some methodical advantages.

The concentrations of estradiol-17 beta (E2) and progesterone (P) were measured in the ampullary and isthmic portions of the fallopian tube of nonpregnant menstruating women and the cyclic fluctuations were related to the concentrations of these hormones in plasma. The steroid concentrations were determined by radioimmunoassays. There was no significant difference in the isthmic and ampullary concentrations of either steroid in any of the menstrual phases. The mean value for E2 was highest in the ovulatory phase and for P during the luteal phase. The tissue (per gm)/plasma (per ml) ratio for the steroid concentrations was above unity in all measurements. The ratio for E2 was highest (isthmus:12, ampulla:8) in the follicular phase and for P (isthmus:26, ampulla:18) during ovulation. Since these highest ratios were attained when plasma steroid concentrations were relatively low they were interpreted as reflections of a maximal receptor contribution.

The role of the macromolecular constituents of human oviductal fluid (hOF) in reproductive physiology is poorly understood. Oviductal fluid contains proteins derived by transudation from serum and those synthesized and secreted by the tubal mucosa. In this communication, we describe purification of hOF-specific proteins. As a first step, serum proteins were removed with an immunoaffinity gel. Fractionation of the proteins unique to hOF was accomplished with DEAE-cellulose chromatography. One of these proteins was obtained in a highly purified state after gel filtration on G-75 Sephadex. This protein of 54 kDa molecular weight had a pI of 4.5 and contained carbohydrate. We propose that this hOF glycoprotein be designated "human oviductin I" (hOV I).

The distribution and concentration of pregnancy-associated plasma protein-A (PAPP-A) in the human fallopian tube were examined by the immunoperoxidase staining technique and radioimmunoassay as part of a detailed study of PAPP-A in the nonpregnant state. PAPP-A-like material was identified in the epithelial cells of the mucosa in all fallopian tube specimens examined (n = 21). The intensity of the staining for PAPP-A was unrelated to the phase of the menstrual cycle. PAPP-A-like material was detected in saline extracts from all tubal tissues (n = 14) but not in any of the sera obtained from the same patients. The tissue concentration (mean +/- standard error of the mean) of immunoreactive PAPP-A varied from 15.2 +/- 1.1 to 30.1 +/- 4.2 micrograms/g protein in different parts of the tubes. No difference in the PAPP-A concentration was found between isthmic, ampullar, and fimbrial part of the tube, but proliferative phase tube seems to contain more PAPP-A than secretory phase tube. The PAPP-A measured in the fallopian tube appears to be similar in molecular size and antigenicity to that of pregnancy.

The study deals with the occurrence of cancer antigen 125 (CA 125) in the normal and neoplastic uterine cervix, endometrium and fallopian tube and its applicability as a tumour marker. CA 125 concentrations were measured in 52 secretion specimens, in cytosol fractions of 97 tissue biopsies and in serum from 47 women with nonmalignant disorders and from 334 patients with carcinomas. High quantities of CA 125 (780-454860 U/ml) were detected in cervical mucus, intra-uterine and tubal fluid, exceeding those in the corresponding serum samples by factors of up to 2000. CA 125 concentrations were 9-53 fold higher in cytosol fractions of normal and neoplastic glandular epithelia of the endocervix and endometrium than in those of cervical squamous epithelia and the cervical wall. Despite similarly high antigen concentrations in normal glandular epithelia and adenocarcinomas serum levels elevated to above 65 U/ml were only found in patients with malignant tumours. The positivity rates in serum increased with tumour extent and were 0-43% for primary and 63-79% for recurrent cervical, endometrial and tubal adenocarcinomas. During long-term follow-up, CA 125 serum concentrations were concordant with the clinical course in 10 out of 11 patients with progressive carcinomas. According to these results, the release of CA 125 into the peripheral blood is apparently dependent on the infiltrative growth and the mass of the tumour rather than on the local tissue concentrations. The clinical use of CA 125 is limited to the detection of advanced adenocarcinomas of the Müllerian duct.

Immunocytes in the female genital tract are found principally in the endocervix. The predominant immunoglobulin produced in this site is IgA and this, together with the presence of secretory component in endocervical epithelium, indicates that a local secretory immune system, similar to that found in the gastrointestinal and respiratory tracts, exists in the endocervix. This local secretory immune system appears to be the major source of immunoglobulins in cervical mucus and the presence of secretory IgA in cervico-vaginal secretions provides an effective protection mechanism against viral and bacterial infections. Secretory IgA also acts non-specifically against exogenous antigens and may, by binding spermatozoal antigens, play a role in immunologically mediated infertility.

1) Serum concentrations of cefoxitin (CFX) was lower than that of cefazolin (CEZ), but the tissue concentrations of CFX were higher in ovary, oviduct and uterus compared with CEZ. 2) CFX was administered to 15 patients with moderate intrapelvic or urinary tract infections at a dose of 4 g per day for 5 to 7 days. The overall results obtained were as follows; excellent in 6 cases, good in 6 cases. The CFX treatment was effective in all patients, 8 cases, with intrapelvic infections. 3) The majority of organisms detected were E. coli (12 strains), and the antimicrobial activity of CFX against them was superior to those of CEZ and CET. 4) No side effects and abnormal laboratory findings were observed. 5) It is considered that CFX will be a useful drug in the field of obstetrics and gynecology.

The localization and distribution of calcitonin gene-related peptide (CGRP) and bombesin/gastrin-releasing peptide (GRP) immunoreactivity were studied in the rat, guinea pig and pig female genital organs with indirect immunohistochemical technique. In the rat, guinea pig and pig, CGRP and GRP immunoreactivities were localized in nerve fibers of the uterus, ovary and oviduct. Generally, CGRP-immunoreactive nerve fibers were intensely stained, while GRP-immunoreactive nerve fibers exhibited moderate immunoreactivity. The number of GRP-immunoreactive nerve fibers in these organs was lower in comparison with that of CGRP-immunoreactive nerve fibers. The pattern of distribution of these nerve fibers was very similar in different genital organs of all species studied. In the uterus of rat, guinea pig and pig, CGRP- and GRP-immunoreactive nerve fibers and nerve bundles were observed in the muscular membrane and around blood vessels. Some delicate CGRP- and GRP-immunoreactive nerve fibers were also present in the submucous layer of the uterus. In the oviduct, CGRP- and GRP-immunoreactive nerve fibers were seen in the muscular membrane, around blood vessels and in the submucous layer. In the ovary, CGRP- and GRP-immunoreactive nerve fibers were distributed in medullary stroma, in close contact with blood vessels and between follicles of different stages of development.

VIP-like immunoreactive material is present in the female reproductive tract, with a distinct pattern of distribution. The highest concentrations of extractable material and immunoreactive nerve fibres were found in the cervix and vagina. In the cervix these fibres were seen below the surface epithelium and around cervical glands as well as in association with blood vessels and smooth muscle bundles. In the vagina the nerve fibres were most abundant in th superficial regions of the lamina propria. Scattered fibres were also present in the rest of the uterus and in the fallopian tubes. Chromatographic evidence indicates that this VIP-like material is of a similar molecular size to that extracted from other organs. Possible roles for VIP in the regulation of myometrial activity and of cervical and vaginal dilation and secretion are proposed.

The regional distributions of neuropeptide Y (NPY), peptide histidine-methionine (PHM), and vasoactive intestinal polypeptide (VIP) immunoreactivities in the human female genital tract have been estimated by specific radioimmunoassays, and their molecular forms determined by chromatography. The localisation and distribution of these three peptides was carried out by immunocytochemistry. The vagina and cervix contain high concentrations of NPY- and VIP-immunoreactive nerves, mainly localised around the vascular and nonvascular smooth muscle. VIP-containing nerves were, in addition, seen beneath the cervical and, in particular, the vaginal epithelium. A comparatively high level of immunoreactive NPY is found in the fallopian tube, mainly around the circular muscle coat. There is evidence that VIP is a neurotransmitter in the female genital tract, and these results suggest a similar role for NPY and PHM.

The authors have used monoclonal estrophilin antibodies and the peroxidase antiperoxidase technique to characterize the distribution of estrogen receptor in the human vagina, uterus, and fallopian tubes. Exclusively nuclear localization of estrogen receptor was observed in epithelial cells, stromal cells of the lamina propria, and smooth muscle cells with both immunohistologic studies and immunoelectron-microscopy studies. The endometrium in various regions of the uterus (uterine isthmus, corpus, and fundus) was stained for estrogen receptor, with similar staining intensities in each of the respective cell types. There was no systematic regional variation in the staining intensity or distribution of cells with stained nuclei. The functionalis of the endometrium showed distinctive variation in the intensity of the staining for estrogen receptor with the menstrual cycle. The staining intensity of both endometrial epithelium and stroma was greatly reduced in the functionalis during the secretory phase. The vaginal epithelium did show some variation with the menstrual cycle, but it was much less than that observed in the functionalis of the endometrium. The basal cells of the vaginal stratified squamous epithelium, strongly stained during the proliferative phase, were less strongly stained during the secretory phase. No variation in the staining intensity for estrogen receptor was observed in different regions of the fallopian tube (isthmus, ampulla, and infundibulum), and the staining intensity varied only minimally with the menstrual cycle. The serosa of the female reproductive tract, connective tissues in the muscularis and in the vicinity of blood vessels, as well as neutrophils, eosinophils, mast cells, and lymphoid cells in the female genital tract were not stained for estrogen receptor.

gamma-Aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) activities were measured in the ovary and the Fallopian tube of rats and compared with brain values. GABA levels in the Fallopian tube were about twice as high as in the brain, while in the ovary they represented only about 5% of the amino acid content of the CNS. In vitro decarboxylation of glutamate, measured via CO2 formation, occurred both in the Fallopian tube and in the ovary. These two organs contained, respectively, 10% and 1% of brain GAD activity. However, the actual formation of GABA from glutamate in a high-speed supernatant was detectable only in the Fallopian tube, where it represented about 5% of brain GAD activity. In contrast with the enzyme present in ovary, liver, anterior pituitary, and kidney, that in the Fallopian tube was quantitatively precipitated by a specific antiserum directed against rat neuronal GAD. Moreover, subcutaneous transplantation resulted in a quantitative decrease of both GABA levels and GAD activity in the Fallopian tube while no change occurred in the ovary, and vagus nerve section induced a 50% decrease of GAD activity in the Fallopian tube, although GABA levels were not significantly altered. The findings suggest an extrinsic GABAergic innervation in the rat Fallopian tube but not in the ovary.

Radioimmunoassay and immunoperoxidase staining were used to study the tissue content and localization of an endometrial protein, placental protein 14, in the human fallopian tube. Placental protein 14 immunoreactivity was found in saline extracts from all fallopian tubes tested (n = 14). In the fimbrial part the placental protein 14 content was higher in the secretory than in the proliferative phase (p less than 0.01). No difference was found in the placental protein 14 content between the isthmic, ampullar, and fimbrial parts of the tube. Immunoperoxidase staining localized placental protein 14 to the ciliated and secretory epithelial cells of the mucosa in all parts of the tube regardless of the phase of menstrual cycle. The occurrence of the same protein in the endometrium and fallopian tube is compatible with the common embryonic origin from the müllerian duct of these tissues.

Hydrocarbons of the human ovary and Fallopian tube have been studied by temperature-programmed gas chromatography. The major compounds present are a series of n-alkanes (C16 to C40), with the addition of iso and anteiso hydrocarbons. The human ovary and Fallopian tube hydrocarbons did not show significant changes during the menstrual cycle.

The synthetic tetrapeptide H-Thr-Pro-Lys-OH, the extract of two-cell hamster embryos, and the oviductal contents devoid of embryos failed to show any in vivo antifertility activity. In addition, the tetrapeptide was not found in the biologic preparations of embryo extract and remaining oviductal contents. These findings are not in agreement with those of previous reports.

The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Müllerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true "tumour marker", but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation.

Chlordecone (10 mg/kg, sc in corn oil) was administered to mature female rabbits once daily for five days. Analysis of oviductal fluid collected from these rabbits over the course of this experiment confirmed the presence of chlordecone. It is reasonable to suggest that chlordecone may reduce mammalian fertility during the preimplantation period by producing deleterious effects on respective gametes and/or the embryo. The mechanisms by which chlordecone may interfere with fertilization and reproduction is discussed.

We sampled oviducts and endometria of 27 cynomolgus macaques during the menstrual cycle and measured the concentration of nuclear and cytoplasmic estrogen receptors in these tissues by exchange assay. We assessed the stage of the cycle by correlating serum estradiol (E2) and progesterone (P), as measured by radioimmunoassay, with the morphological condition of the ovaries, oviducts and endometrium of each animal. We have previously identified a series of oviductal stages that reflected the orderly sequence of cytological changes in the oviduct during the cycle, and we normalized receptor measurements to these stages. The amounts of nuclear and cytoplasmic estrogen receptor in both the oviduct and the endometrium were approximately twofold greater in the follicular phase than in the luteal phase. In the follicular phase, elevated receptor levels were associated with oviductal proliferation and differentiation, as well as with endometrial proliferation. During the luteal phase, lowered levels were correlated with atrophy and dedifferentiation in the oviduct, but with hypertrophy and progestational development in the endometrium. When the luteal phase of one cycle ends and the follicular phase of the next begins, it is a decline in serum P, not a rise in serum E2, that precedes the elevation in estrogen receptor level and the onset of proliferation in the oviduct and endometrium. Proliferation of the reproductive tract and elevations in nuclear estrogen receptor levels during the early follicular phase can therefore be viewed as consequences of the release of the system from antagonism by P.

Monoclonal antibodies to the estrogen receptor (anti-ER) were used to develop an immunocytochemical method to detect ERs in frozen sections of the macaque reproductive tract. Specific nuclear, but not cytoplasmic, staining occurred with two different methods: direct, in which an antiestrophilin -horseradish peroxidase conjugate was used as the first antibody, and indirect, in which a mixture of antiestrophilins was used in the first incubation step. Nuclear staining was absent when various control antibodies replaced the anti-ER. In uteri from spayed monkeys treated with estradiol (E2) for 14 days, nuclear staining was always present. In uteri from similar animals treated for an additional 14 days with E2 and progesterone, nuclear staining was almost completely absent. Mean endometrial nuclear ER levels, measured by an exchange assay, were 5-fold greater in the E2-treated than in the E2-plus progesterone-treated group. In addition, when samples of estrogenized uterus and oviduct were incubated for 60 min in vitro with 100 nM E2, the intensity of nuclear staining increased in parallel with an increase in the concentration of nuclear ER. The nuclei of stromal, smooth muscle, and epithelial cells of the estrogenized oviduct, cervix, and vagina as well as smooth muscle cells of the estrogenized myometrium were also receptor positive. Nontarget tissues, such as duodenum, colon, esophagus, and skeletal muscle, contained no cells that showed specific nuclear staining. Some staining of cytoplasmic and extracellular components occurred in all preparations. These latter reactions were nonspecific, because they were present in many nontarget tissues or when control antibodies replaced the anti-ER. With current methods, only nuclear ERs can be reliably localized in frozen sections of monkey tissues with monoclonal antiestrophilins .

On the basis of present investigations, namely on account of the hydroxyproline determinations and the biomathematical analysis of data, the ageing of the human Fallopian tube with regard to its collagen content can be characterized as follows: Collagen concentration of the oviduct increases slightly and almost linearly up to the 5th decade of woman life. In the 2nd half of the fifth decade, i.e. already in the premenopausal years, this increase is accelerated, then changing into a yet almost linear but stronger rise of the collagen content.

The study of tubal cytosol receptors for estradiol and progesterone shows that they are (in comparison with normal tubes) less in number in post-infection cases (proximal or distal) and increased in number in proximal endometriotic lesions. These variations are only significant for the progesterone receptors. These results are compared with those in the literature, and their implications, concerning hormone treatments used together with microsurgical tubo-plasties, are discussed.

Within the oviduct the maternal humoral immune system can react with the sperm on their way to fertilize the ovum and with preimplantation embryos which express paternal surface antigens. The embryo or sperm is destroyed by antibodies plus complement; thus control of the humoral immune system in the oviduct is advantageous. This paper confirms the absence of whole complement in the oviduct as determined by both in vivo and in vitro hemolytic assays. Further, it is established that there exists within oviductal fluid a concentration-dependent inhibition of complement activity. This inhibitor is heat labile and nondialyzable. Utilizing purification by Sephadex G-200 and ion-exchange chromatography, the complement inhibition was attributed to a family of sulfated glycoproteins secreted by the oviductal epithelium.

[35S] sulfate-labeled oviductal fluid and [35S] sulfate-labeled extracts of cultured oviductal epithelium were obtained from rabbit. Fractionations by gel filtration and ion exchange chromatography indicated both of these sources contained 3 high molecular weight (greater than 200,00 daltons) sulfated mucoproteins, SDS electrophoresis indicated subunits of 71,000 daltons and 32,000 daltons, where only the 71,000 dalton component was sulfated. Ouchterlony analysis indicated complete homology between these oviductal components separated by DEAE chromatography and partial cross-reactivity with a component(s) present in blood plasma. This suggests that cross-reactivity with serum may have masked previous results where investigators were seeking oviduct-specific components, a problem which is overcome in these experiments by use of the oviductal epithelium incubations.