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

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3201-3211 ◽  
Author(s):  
C. Miller ◽  
D.A. Sassoon

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

Development ◽  
1975 ◽  
Vol 34 (2) ◽  
pp. 387-405
Author(s):  
S. A. Iles ◽  
M. W. McBurney ◽  
S. R. Bramwell ◽  
Z. A. Deussen ◽  
C. F. Graham

Mouse eggs were activated with hyaluronidase in vitro and subsequently transferred to the oviduct. In the female reproductive tract they formed morulae and blastocysts which died soon after implantation. Haploid blastocysts were transferred beneath the kidney capsule and here some formed disorganized egg-cylinder structures in a week. Morulae and blastocysts from haploid and diploid parthenogenones were also transferred beneath the testis capsule. Two to four months later the growths which had formed were sectioned. They contained neural tissue, pigment, keratinized epithelium, glandular epithelium, ciliated epithelium, cartilage, bone, muscle, adipose tissue, and haemopoietic tissue. The range of cell types was similar to that produced by fertilized control blastocysts except that the parthenogenones did not form identifiable yolk-sac carcinoma or embryonal carcinomacells. The growths from haploid and diploid parthenogenones in the testis were stained with Feulgen and their DNA content measured. Growths from diploid embryos contained the normal diploid amount of DNA while growths from haploid embryos contained less than this amount. Cell cultures were prepared from the growths. The cells which were investigated contained no Y chromosome, suggesting that they were derived from the embryonic cells rather than the cells of the male host. These cells contained a near diploid chromosome number, although some of them were originally derived from haploid embryos.


2019 ◽  
Vol 15 (1) ◽  
pp. 63-75 ◽  
Author(s):  
Barbara L. Shacklett

As our understanding of mucosal immunity increases, it is becoming clear that the host response to HIV-1 is more complex and nuanced than originally believed. The mucosal landscape is populated with a variety of specialized cell types whose functions include combating infectious agents while preserving commensal microbiota, maintaining barrier integrity, and ensuring immune homeostasis. Advances in multiparameter flow cytometry, gene expression analysis and bioinformatics have allowed more detailed characterization of these cell types and their roles in host defense than was previously possible. This review provides an overview of existing literature on immunity to HIV-1 and SIVmac in mucosal tissues of the female reproductive tract and the gastrointestinal tract, focusing on major effector cell populations and briefly summarizing new information on tissue-resident memory T cells, Treg, Th17, Th22 and innate lymphocytes (ILC), subsets that have been studied primarily in the gastrointestinal mucosa.


2020 ◽  
Author(s):  
Jyoti Goad ◽  
Joshua Rudolph ◽  
Jian-Jun Wei ◽  
Serdar E Bulun ◽  
Debabrata Chakravarti ◽  
...  

AbstractUterine leiomyomas are the most common tumors of the female reproductive tract with significant morbidity that includes excessive bleeding, infertility and pregnancy complications. The origin and cellular composition of leiomyomas is controversial, yet very important in better understanding the pathogenesis of these tumors. We applied single-cell RNA sequencing to better understand cellular heterogeneity of uterine leiomyomas and normal myometrium at the molecular level. Our data reveal previously unknown heterogeneity in the smooth muscle cells, fibroblast cells, and endothelial cells of normal myometrium and leiomyomas. We discovered a novel lymphatic endothelial cell population in uterine leiomyomas and that the immune as well as transcriptional profile of leiomyomas is MED12 genotype-dependent. Moreover, we show that leiomyoma cell moiety is not monoclonal in nature. Our work describes unprecedented single cell resolution of normal uterine myometrium and leiomyoma tumors and provides insight into tumor specific hormone responsiveness and extracellular matrix accumulation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Shuangfeng Chen ◽  
Yuebo Li ◽  
Lili Qian ◽  
Sisi Deng ◽  
Luwen Liu ◽  
...  

Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Endometrioid ovarian cancer, a distinct subtype of epithelial ovarian cancer, is associated with endometriosis and Lynch syndrome, and is often accompanied by synchronous endometrial carcinoma. In recent years, dysbiosis of the microbiota within the female reproductive tract has been suggested to be involved in the pathogenesis of endometrial cancer and ovarian cancer, with some specific pathogens exhibiting oncogenic having been found to contribute to cancer development. It has been shown that dysregulation of the microenvironment and accumulation of mutations are stimulatory factors in the progression of endometrioid ovarian carcinoma. This would be a potential therapeutic target in the future. Simultaneously, multiple studies have demonstrated the role of four molecular subtypes of endometrioid ovarian cancer, which are of particular importance in the prediction of prognosis. This literature review aims to compile the potential mechanisms of endometrioid ovarian cancer, molecular characteristics, and molecular pathological types that could potentially play a role in the prediction of prognosis, and the novel therapeutic strategies, providing some guidance for the stratified management of ovarian cancer.


Endocrinology ◽  
2021 ◽  
Author(s):  
Malak El Sabeh ◽  
Subbroto Kumar Saha ◽  
Sadia Afrin ◽  
Mostafa A Borahay

Abstract The Wnt/β-catenin pathway is upregulated in uterine leiomyomas, the most common benign tumors in the female reproductive tract. Simvastatin is an anti-hyperlipidemic drug, and previous in vitro and in vivo reports showed it may have therapeutic effects in treating leiomyomas. The objective of this study is to examine the effects of simvastatin on the Wnt/β-catenin signaling pathway in leiomyoma. We treated primary and immortalized human leiomyoma cells with simvastatin and examined its effects using RT-qPCR, Western Blotting, and immunocytochemistry. We also examined the effects using human leiomyoma tissues from an ongoing, randomized controlled trial where women with symptomatic leiomyoma received simvastatin (40mg) or placebo for 3 months prior to their surgery. The results of this study reveal that simvastatin significantly reduced the expression of Wnt4 and its co-receptor LRP5. After simvastatin treatment, levels of total β-catenin and its active form, non-phosphorylated β-catenin, were reduced in both cell types. Additionally, simvastatin reduced the expression of Wnt4 and total β-catenin, as well as non-phosphorylated β-catenin protein expression in response to estrogen and progesterone. Simvastatin also inhibited the expression of c-Myc, a downstream target of the Wnt/β-catenin pathway. The effect of simvastatin on non-phosphorylated-β-catenin, the key regulator of the Wnt/β-catenin pathway, was recapitulated in human leiomyoma tissue. These results suggest that simvastatin may have a beneficial effect on uterine leiomyoma through suppressing the overactive Wnt/β-catenin pathway.


2019 ◽  
Vol 10 (1) ◽  
pp. 5-9
Author(s):  
Camila Vasconcelos Ribeiro ◽  
Tábatta Arrivabene Neves ◽  
Glaucia Brandão Fagundes ◽  
Dayana Maria Do Nascimento ◽  
Cleidson Manoel Gomes Da Silva ◽  
...  

Vaginal cytology analysis has been used to evaluate the different stages of estrous cycle of several species; it presents a direct correlation with the animal’s hormonal state and provides essential information about the female reproductive tract conditions. Two staining methods were tested to evaluate the vaginal epithelial cell morphology of nulliparous and multiparous ewes during the estrus period. An intravaginal device impregnated with medroxyprogesterone acetate was kept into 10 nulliparous and 10 multiparous ewes for 14 days for estrus synchronization. Then, the progesterone device was withdrawn, and 300 IU of eCG was administered intramuscularly. Vaginal smears were prepared for posterior staining with Panotico or Giemsa stains when estrus was detected. The cells were classified into nucleated superficial, anucleate superficial, intermediate, parabasal, and basal. The Panotico and Giemsa staining of the different cell types studied were satisfactory. A predominance of intermediate epithelial cells (p<0.05) was found after staining. No difference in percentages of the different types of vaginal epithelial cells between nulliparous and multiparous ewes were found. Therefore, both staining methods were efficient, and a predominance of intermediate cells is found in nulliparous and multiparous ewes during the estrus period.


2020 ◽  
Vol 13 ◽  
pp. 117863612094707
Author(s):  
Wenxia Song ◽  
Qian Yu ◽  
Liang-Chun Wang ◽  
Daniel C Stein

Gonorrhea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection and an urgent public health problem. Humans are the exclusive host, and the genital tract with heterogeneous epithelia is the primary niche of this bacterium, creating unique challenges for understanding its pathogenesis. The cervical tissue explant model that we have developed enabled us to show that the properties of the epithelial cells in the female reproductive tract are the main factors driving gonococcal adaptation. Gonococcal variants that colonize strongly and penetrate poorly, thereby causing asymptomatic infection, survive better in the cervix. Gonococci adapt to different epithelial cell types by varying their surfaces and modulating distinct epithelial cell-cell adhesion complexes through manipulation of host cell signaling. These findings provide critical new insights on the mechanisms by which N. gonorrhoeae adapts to the human mucosal surface and causes asymptomatic infection.


1999 ◽  
Vol 77 (3) ◽  
pp. 451-462 ◽  
Author(s):  
Guy Sainte-Marie ◽  
Bernard Sainte-Marie

Contents of the spermathecae of mated adult snow crabs (Chionoecetes opilio) were examined by light microscopy. The contents could consist of water and three basic types of amorphous matter and of spermatophores. Water was present in the form of large patches or smaller spheres. Of the two major types of amorphous matter, one reacted positively and one negatively to periodic acid - Schiff's reagent (PAS), and one was only, and one predominantly, of male origin. The minor type of amorphous matter was orange and of female origin and could include dark cellular debris. Spermatophores enclosed either immature spermatids, mature spermatids, hitherto unreported spermatozoa, or cell forms intermediate between these three types. Peripheral mature spermatids and spermatozoa had a polarized orientation and were attached to the spermatophore wall. Overall, amorphous matter and spermatophores were topographically segregated by type within a spermatheca, and spermatophores enclosing immature spermatids occurred mostly in PAS-negative amorphous matter. Spermatid differentiation can unfold in the female reproductive tract as well as in the vas deferens, while the transformation of spermatids into spermatozoa was observed only in the female. The diversity of sperm cell types and the ordered placement of semen constituents within the spermatheca suggest that sperm are partitioned for short- or long-term use.


2021 ◽  
Vol 288 (1959) ◽  
pp. 20211553
Author(s):  
Kristin A. Hook ◽  
Qixin Yang ◽  
Leonard Campanello ◽  
Wolfgang Losert ◽  
Heidi S. Fisher

Sperm is one of the most morphologically diverse cell types in nature, yet they also exhibit remarkable behavioural variation, including the formation of collective groups of cells that swim together for motility or transport through the female reproductive tract. Here, we take advantage of natural variation in sperm traits observed across Peromyscus mice to test the hypothesis that the morphology of the sperm head influences their sperm aggregation behaviour. Using both manual and automated morphometric approaches to quantify their complex shapes, and then statistical modelling and machine learning to analyse their features, we show that the aspect ratio of the sperm head is the most distinguishing morphological trait and statistically associates with collective sperm movements obtained from in vitro observations. We then successfully use neural network analysis to predict the size of sperm aggregates from sperm head morphology and show that species with relatively wider sperm heads form larger aggregates, which is consistent with the theoretical prediction that an adhesive region around the equatorial region of the sperm head mediates these unique gametic interactions. Together these findings advance our understanding of how even subtle variation in sperm design can drive differences in sperm function and performance.


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