scholarly journals A NovelIn VivoInfection Model To Study Papillomavirus-Mediated Disease of the Female Reproductive Tract

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Megan E. Spurgeon ◽  
Aayushi Uberoi ◽  
Stephanie M. McGregor ◽  
Tao Wei ◽  
Ella Ward-Shaw ◽  
...  
Keyword(s):  
Uv Radiation ◽  
Murine Model ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Neoplastic Disease ◽  
Wild Type ◽  
Exogenous Estrogen ◽  
Papillomavirus Infection ◽  
Immunocompetent Mice ◽  
Species Specific

ABSTRACTPapillomaviruses exhibit species-specific tropism, thereby limiting understanding and research of several aspects of HPV infection and carcinogenesis. The discovery of a murine papillomavirus (MmuPV1) provides the opportunity to study papillomavirus infections in a tractable,in vivolaboratory model. MmuPV1 infects and causes disease in the cutaneous epithelium, as well as the mucosal epithelia of the oral cavity and anogenital tract. In this report, we describe a murine model of MmuPV1 infection and neoplastic disease in the female reproductive tracts of wild-type immunocompetent FVB mice. Low-grade dysplastic lesions developed in reproductive tracts of FVB mice infected with MmuPV1 for 4 months, and mice infected for 6 months developed significantly worse disease, including squamous cell carcinoma (SCC). We also tested the contribution of estrogen and/or UV radiation (UVR), two cofactors we previously identified as being involved in papillomavirus-mediated disease, to cervicovaginal disease. Similar to HPV16 transgenic mice, exogenous estrogen treatment induced high-grade precancerous lesions in the reproductive tracts of MmuPV1-infected mice by 4 months and together with MmuPV1 efficiently induced SCC by 6 months. UV radiation and exogenous estrogen cooperated to promote carcinogenesis in MmuPV1-infected mice. This murine infection model represents the first instance ofde novopapillomavirus-mediated carcinogenesis in the female reproductive tract of wild-type mice resulting from active virus infection and is also the first report of the female hormone estrogen contributing to this process. This model will provide an additional platform for fundamental studies on papillomavirus infection, cervicovaginal disease, and the role of cellular cofactors during papillomavirus-induced carcinogenesis.IMPORTANCETractable and efficient models of papillomavirus-induced pathogenesis are limited due to the strict species-specific and tissue-specific tropism of these viruses. Here, we report a novel preclinical murine model of papillomavirus-induced cervicovaginal disease in wild-type, immunocompetent mice using the recently discovered murine papillomavirus, MmuPV1. In this model, MmuPV1 establishes persistent viral infections in the mucosal epithelia of the female reproductive tract, a necessary component needed to accurately mimic HPV-mediated neoplastic disease in humans. Persistent MmuPV1 infections were able to induce progressive neoplastic disease and carcinogenesis, either alone or in combination with previously identified cofactors of papillomavirus-induced disease. This new model will provide a much-needed platform for basic and translational studies on both papillomavirus infection and associated disease in immunocompetent mice.

scholarly journals Two groups of Arabidopsis receptor kinases preferentially regulate the growth of intraspecies pollen tubes in the female reproductive tract

2020 ◽  
Author(s):  
Hyun Kyung Lee ◽  
Daphne R. Goring
Keyword(s):  
Pollen Tube ◽  
Reproductive Tract ◽  
Cell Communication ◽  
Pollen Grains ◽  
Pollen Tubes ◽  
Female Reproductive Tract ◽  
Wild Type ◽  
Knockout Mutant ◽  
Receptor Kinases ◽  
Compatible Pollen

SummaryIn flowering plants, continuous cell-cell communication between the compatible male pollen grain/growing pollen tube and the female pistil is required for successful sexual reproduction. In Arabidopsis thaliana, the later stages of this dialogue are mediated by several peptide ligands and receptor kinases that guide pollen tubes to the ovules for the release of sperm cells. Despite a detailed understanding of these processes, a key gap remains on the nature of the regulators that function at the earlier stages. Here, we report on two groups of A. thaliana receptor kinases, the LRR-VIII-2 RK subclass and the SERKs, that function in the female reproductive tract to regulate the compatible pollen grains and early pollen tube growth, both essential steps for the downstream processes leading to fertilization. Multiple A. thaliana LRR-VIII-2 RK and SERK knockout mutant combinations were created, and several phenotypes were observed such as reduced wild-type pollen hydration and reduced pollen tube travel distances. As these mutant pistils displayed a wild-type morphology, the observed altered responses of the wild-type pollen are proposed to result from the loss of these receptor kinases leading to an impaired pollen-pistil dialogue at these early stages. Furthermore, using pollen from related Brassicaceae species, we also discovered that these receptor kinases are required in the female reproductive tract to establish a reproductive barrier to interspecies pollen. Thus, we propose that the LRR-VIII-2 RKs and the SERKs play a dual role in the preferential selection and promotion of intraspecies pollen over interspecies pollen.

scholarly journals Two subgroups of receptor-like kinases promote early compatible pollen responses in the Arabidopsis thaliana pistil

2020 ◽  
Author(s):  
Hyun Kyung Lee ◽  
Daphne R Goring
Keyword(s):  
Arabidopsis Thaliana ◽  
Pollen Tube ◽  
Reproductive Tract ◽  
Cell Communication ◽  
Female Reproductive Tract ◽  
Peptide Ligands ◽  
Wild Type ◽  
Pollen Hydration ◽  
Early Stages ◽  
Compatible Pollen

Abstract In flowering plants, cell–cell communication between the compatible pollen grain/growing pollen tube and the pistil is an essential component for successful sexual reproduction. In Arabidopsis thaliana, the later stages of this dialogue are mediated by several peptide ligands and receptors that guide pollen tubes to the ovules for the release of sperm cells. Despite a detailed understanding of these processes, a key gap remains regarding the nature of the regulators that function at the earlier stages which are essential steps leading to fertilization. Here, we report on new functions for A. thaliana Receptor-Like Kinase (RLK) genes belonging to the LRR-II and LRR-VIII-2 RLK subgroups in the female reproductive tract to regulate compatible pollen hydration and the early stages of pollen tube growth. Mutant pistils for the A. thaliana RKF1 gene cluster were observed to support reduced wild-type pollen hydration and, when combined with the SERK1 and SERK3/BAK1 mutations, reduced pollen tube travel distances occurred. As these mutant pistils displayed a wild-type morphology, we propose that the observed altered compatible pollen responses result from an impaired pollen–pistil dialogue at these early stages.

scholarly journals Quantitative proteomics reveals rapid divergence in the postmating response of female reproductive tracts among sibling species

2020 ◽  
Vol 287 (1929) ◽  
pp. 20201030
Author(s):  
Erin L. McCullough ◽  
Caitlin E. McDonough ◽  
Scott Pitnick ◽  
Steve Dorus
Keyword(s):  
Quantitative Proteomics ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Similar Data ◽  
Reproductive Proteins ◽  
Outgroup Species ◽  
Rapid Divergence ◽  
Female Behaviour ◽  
Species Specific ◽  
Extracellular Environment

Fertility depends, in part, on interactions between male and female reproductive proteins inside the female reproductive tract (FRT) that mediate postmating changes in female behaviour, morphology, and physiology. Coevolution between interacting proteins within species may drive reproductive incompatibilities between species, yet the mechanisms underlying postmating–prezygotic (PMPZ) isolating barriers remain poorly resolved. Here, we used quantitative proteomics in sibling Drosophila species to investigate the molecular composition of the FRT environment and its role in mediating species-specific postmating responses. We found that (i) FRT proteomes in D. simulans and D. mauritiana virgin females express unique combinations of secreted proteins and are enriched for distinct functional categories, (ii) mating induces substantial changes to the FRT proteome in D. mauritiana but not in D. simulans , and (iii) the D. simulans FRT proteome exhibits limited postmating changes irrespective of whether females mate with conspecific or heterospecific males, suggesting an active female role in mediating reproductive interactions. Comparisons with similar data in the closely related outgroup species D. melanogaster suggest that divergence is concentrated on the D. simulans lineage. Our study suggests that divergence in the FRT extracellular environment and postmating response contribute to previously described patterns of PMPZ isolation and the maintenance of species boundaries.

scholarly journals Regulation of porcupine-dependent Wnt signaling is essential for uterine development and function

Reproduction ◽  
2018 ◽  
Vol 155 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Omar Farah ◽  
Steffen Biechele ◽  
Janet Rossant ◽  
Daniel Dufort
Keyword(s):  
Progesterone Receptor ◽  
Wnt Signaling ◽  
X Chromosome ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Wild Type ◽  
Endometrial Gland ◽  
Gfp Reporter ◽  
And Function

Six members of the Wnt family are expressed in the female reproductive tract. Their collective function ensures proper development of the uterus, preparing it for pregnancy during adulthood. Here, we take advantage of the fact thatPorcn,a prerequisite for all Wnt secretion, is located on the X chromosome, to generate females that were mosaic forPorcnthroughout the reproductive tract.Porcnflox/+females were mated with progesterone receptor (Pgr)-Cre males (PgrCre/+) to generate females that were heterozygous for Porcupine in all tissues of the female reproductive tract, resulting in mosaicism due to random X-inactivation. We demonstrated thatPorcnmosaic females are extremely subfertile and exhibit a large spectrum of phenotypes ranging from morphologically normal uteri to uteri with extremely enlarged cystic glands. Decreased fertility in Porcupine mosaic females was not associated with phenotype severity and was observed regardless of whether or not cystic glands were enlarged. By crossing-in a GFP reporter on the wild-type X chromosome, we were able to correlate endometrial gland hyperplasia with a mostlyPorcupinemutant stroma, demonstrating the role of stromal Wnts in the regulation of endometrial gland proliferation. Finally, we demonstrated that fertility issues within mosaic females were due to a reduced response to estrogen and to abnormal Tcf/Lef signaling across the mesometrial-anti-mesometrial axis during the window of implantation.

UTERINE AND PLACENTAL ENZYMES

1964 ◽  
Vol 46 (2) ◽  
pp. 217-229 ◽  
Author(s):  
E. S. E. Hafez
Keyword(s):  
Alkaline Phosphatase ◽  
Reproductive Cycle ◽  
Reproductive Tract ◽  
Enzyme System ◽  
Succinic Dehydrogenase ◽  
Hydrolytic Enzymes ◽  
Carbonic Anhydrase Activity ◽  
Gonadal Hormones ◽  
Female Reproductive Tract ◽  
Species Specific

ABSTRACT The effects of ovariectomy and exogenous gonadal hormones on uterine enzymes have been examined for several laboratory mammals. Qualitative and quantitative measurement of uterine and placental enzymes involve histochemical, cytochemical and biochemical techniques. Enzymes have a wide and characteristic distribution in the female reproductive tract. The pattern of distribution varies showing peculiar species – specific differences in the anatomical localization of the enzyme and its relationship to the reproductive cycle. Progestational responses involve major endometrial growth and striking change in the enzyme system. The amount and biochemical composition of endometrial secretions vary with the stage of reproductive cycle. The placenta contains a complex enzyme system which has been classified into five major groups: hydrases, transferases, oxidoreductases, lyases and isomerases. The passage of many substances across the placental barrier is chemically regulated; the cytoplasm of barrier contains several enzymes and organelles. Carbonic anhydrase activity of the endometrium increases markedly during the luteal phase of the cycle and during pregnancy in the rabbit but not in some other species. Alkaline phosphatase is widely distributed in all types of placenta, in maximal concentration in species producing no fructose. Several hydrolytic enzymes are associated with the small cytoplasmic particles, the lysosomes, β-glucuronidase of the endometrial and glandular epithelia shows cyclical changes with the oestrus cycle. The activity of the succinic dehydrogenase may be an index of the functional status of the epithelial cells. Some enzymes e. g. acid and alkaline phosphatase, 5-nucleotidase and adenosinetriphosphate show a typical »secretion cycle«. The role of certain uterine enzymes in implantation of blastocyst deserves investigation.

scholarly journals Rapid-Release Griffithsin Fibers for Dual Prevention of HSV-2 and HIV-1 Infections

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Kevin M. Tyo ◽  
Amanda B. Lasnik ◽  
Longyun Zhang ◽  
Alfred B. Jenson ◽  
Joshua L. Fuqua ◽  
...  
Keyword(s):  
Murine Model ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vaginal Tissue ◽  
Vaginal Lavage ◽  
Rapid Release ◽  
Hiv 1

ABSTRACT The biologic griffithsin (GRFT) has recently emerged as a candidate to safely prevent sexually transmitted infections (STIs), including human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus 2 (HSV-2). However, to date, there are few delivery platforms that are available to effectively deliver biologics to the female reproductive tract (FRT). The goal of this work was to evaluate rapid-release polyethylene oxide (PEO), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP) fibers that incorporate GRFT in in vitro (HIV-1 and HSV-2) and in vivo (HSV-2) infection models. GRFT loading was determined via enzyme-linked immunosorbent assay (ELISA), and the bioactivity of GRFT fibers was assessed using in vitro HIV-1 pseudovirus and HSV-2 plaque assays. Afterwards, the efficacy of GRFT fibers was assessed in a murine model of lethal HSV-2 infection. Finally, murine reproductive tracts and vaginal lavage samples were evaluated for histology and cytokine expression, 24 and 72 h after fiber administration, to determine safety. All rapid-release formulations achieved high levels of GRFT incorporation and were completely efficacious against in vitro HIV-1 and HSV-2 infections. Importantly, all rapid-release GRFT fibers provided potent protection in a murine model of HSV-2 infection. Moreover, histology and cytokine levels, evaluated from collected murine reproductive tissues and vaginal lavage samples treated with blank fibers, showed no increased cytokine production or histological aberrations, demonstrating the preliminary safety of rapid-release GRFT fibers in vaginal tissue.

scholarly journals Expression of three t-complex genes, Tcp-1, D17Leh117c3, and D17Leh66, in purified murine spermatogenic cell populations

1990 ◽  
Vol 56 (2-3) ◽  
pp. 193-201 ◽  
Author(s):  
K. R. Willison ◽  
G. Hynes ◽  
P. Davies ◽  
A. Goldsborough ◽  
V. A. Lewis
Keyword(s):  
Candidate Genes ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Transmission Ratio Distortion ◽  
Wild Type ◽  
Mendelian Segregation ◽  
T Complex ◽  
Multiple Loci ◽  
Accurate Picture ◽  
Unit Gravity Sedimentation

SummaryTransmission ratio distortion (TRD) is a property of the complete t-haplotype which results in the preferential transmission of the t-haplotype chromosome from heterozygous t/+ males to the majority of the progeny. Available data suggest that in t/+ males, a dysfunction of the wild-type sperm within the female reproductive tract is responsible for the observed deviation from Mendelian segregation ratios. Genetically, Lyon has shown that multiple loci within the t-complex are required for maximum levels of TRD. These loci include multiple t-complex distorters (Teds) which act upon a single t-complex responder (Ter). Testis-expressed genes have been cloned which map to the same subregions of the t-complex as the Teds and Ter and are thus considered candidate genes for the products of these loci. To begin to understand how the products of these loci biochemically control TRD, the expression of three TRD-candidate genes (Tcp-1, D17Leh117c3, and D17Leh66) has been determined in populations of spermatocytes and differentiated spermatids purified to near homogeneity by unit gravity sedimentation. Fractions covering the entire gradient were analysed resulting in a more accurate picture of the precise timing of expression than previously reported. Transcription of all three genes was up-regulated in pachytene primary spermatocytes and persisted at stable levels through the haploid spermatid stages. Significantly, only levels of mRNA encoded by D17Leh66, the candidate gene for Tcr, increased from early round to elongating-stage spermatids. If this pattern of expression does, in fact, represent Tcr, these data provide the first direct evidence that wild-type and t-haplotype Tcr elements could be differentially expressed in haploid spermatids.

Effect of Contraceptive Steroids on the Endometrium of Guinea Pig: SEM study

1977 ◽  
Vol 35 ◽  
pp. 668-669
Author(s):  
Mai M. Said ◽  
Ramesh K. Nayak ◽  
Randall E. McCoy
Keyword(s):  
Guinea Pig ◽  
Reproductive Tract ◽  
Three Dimensional ◽  
Female Reproductive Tract ◽  
Human Female ◽  
Surface Ultrastructure ◽  
Transmission Electron ◽  
Sem Study ◽  
Uterine Mucosa ◽  
Group 1

Burgos and Wislocki described changes in the mucosa of the guinea pig uterus, cervix and vagina during the estrous cycle investigated by transmission electron microscopy. More recently, Moghissi and Reame reported the effects of progestational agents on the human female reproductive tract. They found drooping and shortening of cilia in norgestrel and norethindrone- treated endometria. To the best of our knowledge, no studies concerning the effects of mestranol and norethindrone given concurrently on the three-dimensional surface features on the uterine mucosa of the guinea pig have been reported. The purpose of this study was to determine the effect of mestranol and norethindrone on surface ultrastructure of guinea pig uterus by SEM.Seventy eight animals were used in this study. They were allocated into two groups. Group 1 (20 animals) was injected intramuscularly 0.1 ml vegetable oil and served as controls.

Surface ultrastructure of danazol treated rat endometrium: A SEM study

1983 ◽  
Vol 41 ◽  
pp. 556-557
Author(s):  
R.P. Apkarian ◽  
J.S. Sanfilippo
Keyword(s):  
Cross Sections ◽  
Reproductive Tract ◽  
Preliminary Investigation ◽  
Breast Disease ◽  
Distal Segment ◽  
Uterine Horn ◽  
Female Reproductive Tract ◽  
Ultrastructural Changes ◽  
Cycle Phase ◽  
Sprague Dawley

The synthetic androgen danazol, is an isoxazol derivative of ethisterone. It is utilized in the treatment of endometriosis, fibrocystic breast disease, and has a potential use as a contraceptive. A study was designed to evaluate the ultrastructural changes associated with danazol therapy in a rat model. The preliminary investigation of the distal segment of the rat uterine horn was undertaken as part of a larger study intended to elucidate the effects of danazol on the female reproductive tract.Cross-sections (2-3 mm in length) of the distal segment of the uterine horn from sixteen Sprague-Dawley rats were prepared for SEM. Ten rats in estrus served as controls and six danazol treated rats were noted to have alterations of the estrus cycle i.e. a lag in cycle phase or noncycling patterns. Specimens were fixed in 3% glutaraldehyde in 0.05M phosphate buffer containing CaCl2 at pH 7.0-7.4 and chilled to 4°C. After a brief wash in distilled water, specimens were passed through a graded series of ethanol, critical point dryed in CO2 from absolute ethanol, and coated with 6nm Au. Observations were made with an IS1-40 SEM operated at 15kV.

The application of electron microscopy to diagnosis in gynecologic neoplasms and tumor-like conditions

1984 ◽  
Vol 42 ◽  
pp. 102-105
Author(s):  
Lawrence M. Roth
Keyword(s):  
Electron Microscopy ◽  
Reproductive Tract ◽  
Malignant Tumors ◽  
Frozen Section ◽  
Cost Effective ◽  
Female Reproductive Tract ◽  
Ultrastructural Examination ◽  
Specific Diagnosis ◽  
Potential Value ◽  
Gynecologic Neoplasms

The female reproductive tract may be the site of a wide variety of benign and malignant tumors, as well as non-neoplastic tumor-like conditions, most of which can be diagnosed by light microscopic examination including special stains and more recently immunoperoxidase techniques. Nevertheless there are situations where ultrastructural examination can contribute substantially to an accurate and specific diagnosis. It is my opinion that electron microscopy can be of greatest benefit and is most cost effective when applied in conjunction with other methodologies. Thus, I have developed an approach which has proved useful for me and may have benefit for others. In cases where it is deemed of potential value, glutaraldehyde-fixed material is obtained at the time of frozen section or otherwise at operation. Coordination with the gynecologic oncologist is required in the latter situation. This material is processed and blocked and is available if a future need arises.

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