Uterus Tissues Research Articles

Molecular dynamics simulation of human neurohypophyseal hormone receptors complexed with oxytocin—modeling of an activated state

The neurohypophyseal hormone oxytocin (CYIQNCPLG-NH(2), OT) is involved in the control of labor, secretion of milk and many social and behavioral functions via interaction with its receptors (OTR) located in the uterus, mammary glands and peripheral tissues, respectively. In this paper we propose the interactions responsible for OT binding and selectivity to OTR versus vasopressin ([F3,R8]OT, AVP) receptors: V1aR and V2R, all three belonging to the Class A G protein-coupled receptors (GPCRs). Three-dimensional models of the activated receptors were constructed using a multiple sequence alignment and the activated rhodopsin-transducin (MII-Gt) prototype [Slusarz and Ciarkowski, 2004] as a template. The 1 ns unconstrained molecular dynamics (MD) of three pairs of receptor-OT complexes (two complexes per each receptor) immersed in the fully hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer was conducted in the AMBER 7.0 force field. The relaxed models of ligand-receptor complexes were used to identify the putative binding sites of OT. The stabilizing interactions with conserved Gln residues in all complexes were identified. The nonconserved hydrophobic residues were proposed as responsible for OTR-OT selectivity and ligand recognition. These results provide guidelines for experimental site-directed mutagenesis and if confirmed, they may be helpful in designing new selective OT analogs with both agonistic or antagonistic properties.

Scattering signatures for some human tissues using synchrotron radiation

AbstractAt photon energies below 100 keV, coherent scatter becomes important and because of its sharply forward peaked nature, it is the dominant interaction at small angles. Further, in the momentum transfer region above 0.5 Å−1, free atom form factors are sufficient to describe coherent scattering. The angular distribution of the coherent scattering carries detailed information about the object and can be used as a signature of the tissue type of the object. The aim of this work was to analyze the scattering properties of different human tissues according to histological classifications. The coherent scattering signatures of healthy and neoplastic breast, uterus and kidney tissues were measured using x‐ray synchrotron radiation at the XRD2 beamline at the Brazilian Synchrotron Light Laboratory (LNLS). Copyright © 2005 John Wiley & Sons, Ltd.

Cellular Distribution, Post-translational Modification, and Tumorigenic Potential of Human Group III Secreted Phospholipase A2

Human group III secreted phospholipase A(2) (sPLA(2)-III) consists of a central group III sPLA(2) domain flanked by unique N- and C-terminal domains. We found that the sPLA(2) domain alone was sufficient for its catalytic activity and for its prostaglandin E(2) (PGE(2))-generating functions in various cell types. In several if not all cell types, the N- and C-terminal domains of sPLA(2)-III were proteolytically removed, leading to the production of the form containing only the sPLA(2) domain, which could be further N-glycosylated at two consensus sites. Immunohistochemistry demonstrated that sPLA(2)-III was preferentially expressed in the microvascular endothelium in human tissues with inflammation, ischemic injury, and cancer. In support of this, sPLA(2)-III was induced in cultured microvascular endothelial cells after stimulation with proinflammatory cytokines. Expression of sPLA(2)-III was also associated with various tumor cells, and colorectal cancer cells transfected with sPLA(2)-III exhibited enhanced PGE(2) production and cell proliferation, which required sPLA(2)-III catalytic activity. When implanted into nude mice, the sPLA(2)-III-transfected cells formed larger solid tumors with increased angiogenesis compared with control cells. Moreover, small interfering RNA for sPLA(2)-III significantly reduced PGE(2) production and proliferation of colorectal cancer cells. Taken together, these results reveal unique cell type-specific processing and N-glycosylation of sPLA(2)-III and the potential role of this enzyme in cancer development by stimulating tumor cell growth and angiogenesis.

Design, synthesis and evaluation of racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides as novel uterine relaxants

Novel 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides were designed based on the pharmacophore for potent uterine relaxant activity and by utilizing the principles of structural hybridization. The designed molecules were synthesized as racemates by a novel route and were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP-releasing potential was studied using rat uterus tissue homogenates by the cAMP [ 3H] assay, and cardiac stimulant potential was evaluated on isolated guinea pig right atrium. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP-releasing potential was slightly less, while their cardiac stimulant potential was insignificant as compared to isoxsuprine hydrochloride.

Cutaneous clear cell myomelanocytic tumour: a new member of the growing family of perivascular epithelioid cell tumours (PEComas). Clinicopathological and immunohistochemical analysis of seven cases

To analyse seven cases of cutaneous myomelanocytic tumour histologically and immunohistochemically. Perivascular epithelioid cell tumours (so-called PEComas) are rare and recently delineated neoplasms occurring in the lung, kidney, pancreas, uterus, falciform ligament, vulva, heart, prostate and soft tissues. PEComas are characterized by a perivascular location of neoplastic cells showing a broad spectrum of epithelioid and spindled cells with clear, and granular pale eosinophilic cytoplasm, and a variable expression of melanocytic and muscle markers, whereas S100 protein and cytokeratins are usually absent. We report seven cases of cutaneous myomelanocytic tumour arising on the lower (six cases) and upper (one case) extremities of female adults (age range 30-66 years). In all cases an ill-defined dermal lesion with extension into subcutaneous tissue was noted. The neoplasms contained numerous blood vessels with a lace-like pattern and slightly thickened vessel walls, and were composed of perivascular epithelioid cells containing clear or focally granular pale eosinophilic cytoplasm and round vesicular nuclei with small, sometimes slightly enlarged nucleoli. Increased proliferative activity and tumour necrosis were not seen. Immunohistochemically, tumour cells stained positively for HMB-45, microphthalmia transcription factor, and NKIC3 in all cases, whereas perivascular expression of alpha-smooth muscle actin and focal positivity for desmin were noted in one case each only. Two out of four cases tested stained focally positive for calponin. No expression of S100 protein and pancytokeratin was present. Despite incomplete/marginal excision in three cases none of the neoplasms has recurred locally so far. With the presented series of cutaneous myomelanocytic tumours the clinicopathological spectrum of PEComas is expanded.

Sinonasal Leiomyoma: Report of 2 Cases

Leiomyomas are benign smooth-muscle tumors that are common in the alimentary tract, uterus, skin, and subcutaneous tissue. They are very uncommon in the upper respiratory tract and rare in the nasal cavity and paranasal sinuses. To the best of our knowledge, only 23 such cases have heretofore been published in the literature. We report 2 new cases of sinonasal leiomyoma that originated at different sites in the nasal cavity. We also discuss the various investigative and therapeutic modalities available.

126 EFFECTS OF THE REPRODUCTIVE STATUS ON DEVELOPMENTAL COMPETENCE OF RECIPIENT OOCYTES AFTER SOMATIC CELL NUCLEAR TRANSFER IN CAT

The reproductive status of donor cat has been suggested to influence developmental competence of the oocytes after IVM/IVF (Karja et al. 2002 Theriogenology 57, 2289–2298). This study was conducted to examine the effect of the reproductive cycle stage of cat ovaries supplying recipient oocytes for nuclear transfer (NT) on the developmental competence of the oocytes after somatic cell nuclear transfer. Cat ovaries were collected at local veterinary clinics and stored at 35°C for a short period (1–6 h). Based on the presence or absence of follicles and corpora lutea, the ovarian pairs collected were classified into the inactive, follicular or luteal stages. Cumulus-oocyte complexes (COCs) were obtained from ovaries at each stage of the reproductive cycle by mincing/dissection and matured in vitro for 24 h, as previously described (Karja et al. 2002 Theriogenology 57, 2289–2298). In vitro matured oocytes from ovaries at the inactive (n = 114), follicular (n = 124), and luteal (n = 126) stages were mechanically enucleated in PBS supplemented with 5 μL mL−1 of cytochalasin B and 3 mg mL−1 BSA, and reconstructed with fibroblast cells derived from uterus tissue. The couplets were fused in Zimmerman medium with a single DC pulse of 1.5 kV cm−1 for 50 μs. The successfully fused couplets were activated by a 5-min exposure to 10 μg mL−1 calcium ionophore A23187 in MK1 medium (Kanda et al. 1998 J. Vet. Med. Sci. 60, 423–431) followed by 5 h of incubation in MK1 medium supplemented with 10 μg mL−1 cycloheximide. The NT embryos were cultured in MK1 medium supplemented with 4 mg mL−1 BSA at 38.0°C in a humidified atmosphere of 5% CO2 in air. At 72 h of culture, all cleaved NT embryos were transferred to fresh MK1 medium supplemented with 5% fetal calf serum for an additional 4 days to evaluate their ability of development to the blastocyst stage. Data were analyzed by ANOVA. There were no significant differences (P > 0.05) among the fused oocytes derived from ovaries at the inactive, follicular, and luteal stages with respect to the percentages of cleavage (64.4%, 69.4%, and 74.5%, respectively) and blastocyst formation (17.4%, 21.0%, and 12.0%, respectively). These results indicate that the reproductive cycle stage of cat ovaries has no apparent effect on the development at competence of recipient oocytes after somatic cell nuclear transfer.

Identification of Immunoreactive Ghrelin and its mRNA in the Oviduct of Laying Japanese Quail, Coturnix japonica

The aim of this study was to determine whether ghrelin is produced in the oviduct of Japanese quail. Japanese quail laying hens and 20-days-old immature ones were used. The matured birds were examined at two different times of ovulation cycle, namely just after oviposition (preovulation group) and 6h after oviposition (5-h-postovulation group). The oviductal tissues were processed for paraffin sections and immunostained for ghrelin. The expression of ghrelin mRNA in the oviduct of preovulation group was examined by RT-PCR. In the preovulation group, we observed positive immunostaining of ghrelin in the epithelial cells of the mucosal folds in the infundibulum (tubular region) and magnum. The density of immunoreactive products was stronger in the cephalic and middle parts than in the caudal part in the magnum. No immunoreactivity was observed in the tissues of isthmus, uterus and vagina. RT-PCR analysis confirmed that mucosal tissue of the infundibulum and magnum, but not other oviductal segments, expressed mRNA for ghrelin. The intensity of immunostaining for ghrelin in the infundibulum, cephalic and middle parts of magnum was reduced in 5-h-postovulation group compared with preovulation group. In immature birds, no immunoreactivity for ghrelin was observed in both magnum and uterus tissues. These results suggest that the mucosal epithelium in the oviduct of quail hens produces ghrelin, and it may be secreted during the passage of eggs through oviduct. Ghrelin may not be produced in the oviduct of immature birds, and the production may occur in association with a development of oviduct.

Oestrogen-receptors (ER) are likely to be promiscuous: Wider role for oestrogens and mimics

The anti-breast cancer drug tamoxifen that binds to ER is metabolised in human liver by CYP2D6 isoenzyme, whilst the metabolism of 17beta-oestradiol (by hydroxylation) is by phase I biotransformation in the liver to 2-hydroxyoestradiol and to 4-hydroxyoestradiol respectively by two isoenzymes of this mixed function oxidase CYP cytochromes P450 (EC 1.14.14.1); CYP1A2 and by CYP1B1. Nevertheless, it appears that the receptor (AhR) itself causes the expression of oestrogen-regulated target genes (studied by binding of dioxin). This is the result of an unknown signalling mechanism at the genome that is triggered directly by this receptor by binding promiscuously to ER (alpha or beta) sites. This has been observed even in the absence of oestrogens or mimics therefore in genome-binding investigations of target tissues such as uterus: oestrogen-receptor (ER) is likely to be promiscuous therefore. Furthermore, AhR (polycyclic aromatic hydrocarbon receptor), when activated by the binding of aromatic hydrocarbons (Ah) forms a complex with the aryl hydrocarbon nuclear-translocator chaperone protein (Arnt). It is this binding to xenobiotic response elements in DNA that initiates expression of the appropriate oestrogen-regulated target-genes in the uterus and other target tissues (including mammary, ovaries, and brain). The likely promiscuity of oestrogen receptors is proposed to be the cause of numerous side effects when oestrogen is involved in therapy, these can be manifest in hormone replacement therapy (HRT) and in the incorporation of synthetic oestrogens in the wide varieties of oral contraceptives now available.

First Description of a PEComa (Perivascular Epithelioid Cell Tumor) of the Colon: Report of a Case and Review of the Literature

We describe a young female patient suffering from a PEComa (perivascular epithelioid cell tumor) of the cecum, incidentally found at an examination made by her family physician. The perivascular epithelioid cell tumor is a very rare tumor, until today reported in a few cases in falciform ligament, uterus, jejunum, terminal ileum, rectum, liver, kidney, lung, pancreas, prostate, and soft tissue of the thigh. This tumor is part of a new group of tumors, comprised of angiomyolipoma, lymphangiomyolipoma, and clear-cell myomelanocytic "sugar" tumor. Defined by coexpression of melanocytic (HMB-45) and muscle markers (smooth muscle actin and desmin) the perivascular epithelioid cell tumor does not have predictable histopathologic behavior. Some cases of metastasis are described, comorbidities such as tuberous sclerosis of the brain "Bourneville" and lymphangioleiomyomatosis have to be excluded. The therapy consists of the radical resection. An adjuvant therapy is not known. Recommended is a close and long-term follow-up clinically and by CT scan.

The force required to remove the frameless 0-suture IUD anchoring system: comparison between pre- and postmenopausal women

Objective The objective of this short communication is to measure and compare the force needed to remove the implanted “0-suture” GyneFix® intrauterine contraceptive device (IUD) and the “0-suture” FibroPlant™-LNG intrauterine system (IUS) from the uterus of pre- and postmenopausal women. Study design A nonrandomized comparative study in 119 pre- and postmenopausal women. A dynamometer (Pesola®) was used to measure the removal force in newtons. Results The results of this study show a mean removal force of 8.5 and 9.5 newtons, respectively (range, 3–11 and 4.5–11), in pre- and postmenopausal women, which is significantly different (p = 0.003). Conclusions The force needed to remove the IUD/IUS anchored in the myometrium of the uterine fundus of pre- and postmenopausal women is higher than the removal force found in previous studies in which the IUD consisted of a slightly thinner anchoring thread (00 instead of 0 suture). The statistically significantly different removal force between the two groups has no clinical implications. The difference may reflect the increased compactness of the uterine tissue in the postmenopausal uterus.

Brucellosis in wild boar (Sus scrofa) in the Republic of Croati

During the years 2001 and 2002 on seven localities in Croatiaa survey on the prevalence of brucellosis in wild boar was carried out. The survey included 271 (52.7%) female and 243 (47.3%) male animals between 7 months and 4 years of age and weighing from 14 to 135 kg. On that occasion 514 blood samples of wild boar were serologically analysed. For serological analysis indirect enzyme immunoassay (iELISA), Rose Bengal test (RBT), complement fixation test (CFT) and slow agglutination test (SAT) were used. In all of the wild boar from all of the localities investigated positive reactions to brucellosis were established. Most of the positive reactions were established by iELISA (13.6%), then by RBT (11.5%), CFT (10.5%) and SAT (8.9%). Tissue samples of 106 animals: testes samples from 67 animals, uterus tissue from 38 animals and 5 fetuses of piglets from 1 mother were analysed bacteriologically. Brucella suis biovar 2 was isolated from 18 (17.0%) animals that originated from all of the localities investigated. Isolates were identified by PCR using BRU-UP and BRU-LOW primers specific for genus Brucella and primers specific for IS711. Based on our results it could be concluded that in Croatia wild boar are natural vector and/or reservoirs of B. suis biovar 2. This permanent risk factor is hazardious for domestic and wild animals in theRepublic ofCroatia.

Nongonadal LH receptors, their involvement in female reproductive function and a new applicable approach

Luteinising hormone (LH) and human chorionic gonadotropin (hCG) share a common receptor in gonadal cells. The receptors have also been detected in several nongonadal but reproduction-associated tissues of pigs, cattle, and other species including the uterus (myometrium, endometrium), oviduct, cervix, blood vessels, mammary gland and other tissues. The main role of LH/hCG receptors in the myometrium is stimulation of growth and hyperplasia, and relaxation of uterine motility; hCG also boosts blood flow in the uterine artery. LH and hCG can increase production of prostaglandins in the endometrium, oviduct, and blood vessels. We suggest that the preovulatory surge of LH plays an important role in controlling oviductal contractions. Awareness of LH binding to many tissues of the female reproductive tract and integration with embryonic factors may lead to the elaboration of new strategies for improved reproductive efficiency in domestic species. Mammary glands also possess LH/hCG receptors through which gonadotropins can affect the metabolism of steroid hormones and could play an inhibitory role in mammary carcinogenesis and in the growth of breast tumours. A novel approach to target and ablate carcinoma cells through LH receptors is described.

How to understand estrogen signaling from the phenotypes of ERalpha and ERbeta knockout mice.

When ERα knockout mice were created in 1993 (Lubahn et al. 1993), no one was aware of the presence of ERβ and it was assumed that the phenotype of these animals revealed loss of estrogen signaling. We now know that this first ERα knockout was not perfect and that some truncated forms of ERα are expressed in these mice (Couse et al. 1995). We also know that there is another ER, ERβ (Kuiper et al. 1996), so that some estrogen signaling is still intact in ERα -/- mice. Since the development of the original ERα knockout mice, ERβ knockout mice (Krege et al. 1998) and double knockout mice (Ogawa et al. 2000) have been created and intensively examined and the phenotypes often reviewed (Mueller and Korach 2001; Couse et al. 2001; Emmen et al. 2003; Hewitt and Korach 2003). Clearly, disruption of ERa results in severe dysfunction of the ovary, uterus, mammary gland, pituitary and adipose tissue, i.e., the classical estrogen target tissues. At first ERβ was thought to be not very important physiologically because the classical estrogen target tissues of the ERβ -/- mice are much less affected than they are in the ERα -/- mice. It was only when the ERβ -/- mice were examined more carefully that it became apparent that there were many more estrogen target tissues that had been suspected (Nilsson et al. 2001).

Effects of food restriction and pregnancy on the expression of insulin-like growth factors-I and -II in tIssues from guinea pigs.

The insulin-like growth factor (IGF) system is subjected to pregnancy-associated changes in the circulation and is suggested to be of importance for partitioning of nutrients between the mother and the foetus. Interestingly, maternal undernutrition alters the pregnancy-associated changes, with possible adverse consequences for the mother and the foetus. However, it is not known how malnutrition and pregnancy alter the expression of mRNA for IGFs locally in different tIssues. The aims of this study were to investigate where IGF-I and IGF-II are expressed in guinea pigs and how this expression is altered during food restriction and pregnancy. Ad libitum-fed and food-restricted (fed 70% of the ad libitum-fed intake four weeks before pregnancy and throughout the study) guinea pigs were mated. On day 40 of pregnancy and on the corresponding day for virginal females the animals were killed. mRNA for IGF-I and IGF-II was analysed in various organs/tIssues by solution hybridisation. mRNA for IGF-I was expressed in high amounts in uterus, liver and adipose tIssues. The expression was not affected by food restriction, but was increased in liver and adipose tIssue and decreased in uterus by pregnancy. mRNA for IGF-II was expressed in high amounts in the placenta and liver. In the placenta the expression was decreased by food restriction. Pregnancy increased the levels of mRNA for IGF-II in the liver. Food-restricted dams had smaller foetuses and placentas. In conclusion, this study indicates an important role for the adipose tIssue during gestation, not only as an energy store but also as an endocrine tIssue expressing IGF-I. The decreased expression of IGF-II in the placenta due to food restriction is suggested to have adverse effects on placental structure and function.

Activity and response to serum of the mammalian thyroid hormone deiodinase 3 gene promoter: identification of a conserved enhancer

Dio3 is an imprinted gene that codes for the type 3 deiodinase (D3), a conserved selenocysteine-containing enzyme that degrades thyroid hormones (TH) into inactive metabolites. D3 is partially responsible for the very low TH levels that are found in utero as it is highly expressed in mammalian uterus, placenta, and fetal tissues. For this reason, it is presumed that D3 protects the developing fetus from high, adult-like levels of TH. To further understand the regulation of D3 expression, we analyzed the promoter activity of 6 kb of 5′-flanking regions of the human and mouse Dio3, by transient transfection studies. Both mouse and human Dio3 promoters are markedly responsive to serum and, to a lesser extent, to phorbol esters and fibroblast growth factor, but only in a cell line in which the endogenous Dio3 mRNA is also responsive to those factors. In addition, we identified a conserved enhancer located 3′ of the gene containing putative AP-1 and serum response elements, and that further increases the serum responsiveness of the Dio3 promoter in a cell-specific manner. The cell-specific serum response of the Dio3 promoter and the identified enhancer may play critical roles in the regulation of gene expression at this imprinted locus.

Selective estrogen receptor modulators.

Because of recent concerns about the long-term risks of estrogen replacement therapy in postmenopausal women, there is growing interest in a group of compounds known as selective estrogen receptor modulators (SERMs). The SERMs bind to estrogen receptors and have tissue-specific effects that allow them to function as estrogen agonists in some tissues and estrogen antagonists in other tissues. There are four SERMs currently marketed in the United States. These include the triphenylethylenes--clomiphene citrate (Clomid), tamoxifen, and toremifene--and the benzothiophene, raloxifene. Clomid is used primarily in the treatment of infertility. Tamoxifen is indicated for the treatment and prevention of breast cancer. It has an estrogen antagonist effect on breast tissue, but an estrogen-like effect on lipids, bone, and the endometrium. Toremifene has an antagonist/agonist profile similar to that of tamoxifen. Raloxifene is approved for the prevention of osteoporosis in postmenopausal women. It is thought to be an estrogen antagonist on the uterus and breast tissues and an estrogen agonist with respect to bone and serum lipids.

Molecular assays to profile 10 estrogen receptor beta isoform mRNA copy numbers in ovary, breast, uterus, and bone tissues.

Estrogens regulate various biological processes in a diverse range of reproductive and nonreproductive tissues through two genetically distinct but structurally related high affinity nuclear receptors, the estrogen receptor alpha and beta (ERalpha and ERbeta). The physiological significance of the presence of two ERs that have redundant functions is not known. Several unique properties of ERbeta together with its distinct expression patterns are considered to be, in part, the basis for diverse functional actions of estrogens and opposing actions of selective estrogen receptor modulators (SERMs) in different tissues. To understand how relative expression levels of two ERs correlate to seemingly dissimilar actions of estrogens and SERMs, quantitative methods are required that can precisely measure the levels of every isoform. Previously, methods to quantify eight ERalpha isoforms have been described [Poola I. (2003) Anal. Biochem. 314, 217-226]. In this article, real-time PCRbased molecular assays are described that can distinguish and quantify as low as 100 copies of 10 ERbeta isoform mRNAs, the ERbeta1, ERbeta2, ERbeta4, ERbeta5, and ERbeta exon 2Delta, exon 3Delta, exon 4Delta, exon 5Delta, exon 6Delta, and exons 5-6Delta. Each isoform mRNA is quantified using a specific primer pair and a 5'FAM (carboxy-fluorescein)- and 3'TAMARA (6-carboxy tetraethyl-rhodamine)-labeled probe and in comparison with a standard curve constructed with known copy numbers of its respective reverse transcribed cRNA. The devised assays were applied to profile 10 ERbeta isoforms in four estrogen-sensitive tissues-ovary, breast, uterus, and bone. The sensitivity of detection of each isoform in these tissues varied from picograms to nanograms of reverse-transcribed total RNA depending on the isoform and the tissue. The results presented also show that each tissue has a distinct profile of 10 isoform mRNAs. Interestingly, ERalpha- negative breast cancer cell lines and tumors expressed significant amounts of ERbeta isoforms suggesting that mitogenic stimulation by estrogen exists in these tissues. Bone tissues expressed several isoforms, although wild type was not present. In addition to the assay development, evidence is presented to demonstrate for the first time that ERbeta4 and ERbeta5 are full length receptors, contrary to previous reports that they are short receptors of exon 7-8.

Chronic intrauterine and fetal infection with Gardnerella vaginalis

Objective: We sought to develop a model of chronic intrauterine and fetal infection with Gardnerella vaginalis.Study Design: The uterine horns of pregnant New Zealand White rabbits were inoculated on day 21 of gestation with either 107 colony-forming units (cfu) of G vaginalis or saline solution. At necropsy, cultures were taken from blood, uterus, amniotic fluid, and fetal tissues. Amniotic fluid was assayed for tumor necrosis factor (TNF)-α by bioassay. Maternal and fetal tissue samples were evaluated using the histologic index score. A P value <.05 was considered significant. Results: Compared with saline solution–inoculated animals, the G vaginalis group had significantly more positive cultures from uterus, amniotic fluid, and fetal brain and lung (P =.02 to <.01). For the G vaginalis group, mean TNF-α levels and fetal brain scores increased significantly over time (P <.001 for both). Conclusion: Chronic intrauterine and fetal infection with G vaginalis is accompanied by progressive increases in amniotic fluid TNF-α concentrations and fetal brain histologic index scores. (Am J Obstet Gynecol 2002;187:1263-6.)

Presence of caprine arthritis–encephalitis virus (CAEV) proviral DNA in genital tract tissues of superovulated dairy goat does

Transmission of caprine arthritis–encephalitis virus (CAEV) is not completely understood and the vertical route of infection from the goat to the embryo or to the fetus needs to be investigated. This route of infection involves the presence of CAEV in the genital tract tissues. Prior studies have detected CAEV-infected cells in genital secretions and in flushing media recovered during embryo collection from infected goats. To specify the origin of these cells, we conducted a double-nested polymerase chain reaction (PCR) test on embryo flushing media and on mammary gland, mammary lymph node, synovial membrane, pelvic lymph node, uterus and oviduct tissues from 25 CAEV-infected (blood PCR positive) embryo donor goats for the presence of CAEV proviral DNA.The presence of proviral DNA was found in 22 of 25 mammary gland samples, 14 of 25 uterus samples, and in 16 of 25 oviduct samples. Nineteen of 25 goats had at least one positive genital tract sample. Flushing media from 11 goats were PCR positive. All goats with positive-flushing media were oviduct positive. Of this group of does, except for 1 of the 11, infection of flushing media correlated with infection of almost all the other tissues examined. The frequency of positive tissues for flushing media-positive goats (61/66; 92%) was significantly higher than that for flushing media-negative goats (50/84; 60%) (P<0.01).This study demonstrated the presence of CAEV-infected cells in the goat genital tract. The presence of CAEV-infected cells in the uterus and oviducts suggests potential for vertical transmission of CAEV from doe to embryo or fetus.