Involvement of a matrix metalloproteinase in MIS-induced cell death during urogenital development

Development ◽  
2002 ◽  
Vol 129 (6) ◽  
pp. 1487-1496 ◽  
Author(s):  
Lori M. Roberts ◽  
Jenny A. Visser ◽  
Holly A. Ingraham
Keyword(s):  
Cell Death ◽  
Matrix Metalloproteinase ◽  
Target Genes ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Normal Male ◽  
The Matrix ◽  
Candidate Target ◽  
Sexually Dimorphic Expression ◽  
Urogenital Development

Programmed cell death of the Müllerian duct eliminates the primitive female reproductive tract during normal male sexual differentiation. Müllerian inhibiting substance (MIS or AMH) triggers regression by propagating a BMP-like signaling pathway in the Müllerian mesenchyme that culminates in apoptosis of the Müllerian duct epithelium. Presently, the paracrine signal(s) used in this developmental event are undefined. We have identified a member of the matrix metalloproteinase gene family, Mmp2, as one of the first candidate target genes downstream of the MIS cascade to function as a paracrine death factor in Müllerian duct regression. Consistent with a role in regression, Mmp2 expression was significantly elevated in male but not female Müllerian duct mesenchyme. Furthermore, this sexually dimorphic expression of Mmp2 was extinguished in mice lacking the MIS ligand, suggesting strongly that Mmp2 expression is regulated by MIS signaling. Using rat organ genital ridge organ cultures, we found that inhibition of MMP2 activity prevented MIS-induced regression, whereas activation of MMP2 promoted ligand-independent Müllerian duct regression. Finally, MMP2 antisense experiments resulted in partial blockage of Müllerian duct regression. Based on our findings, we propose that similar to other developmental programs where selective elimination or remodeling of tissues occurs, localized induction of extracellular proteinases is critical for normal male urogenital development.

Capacitation mechanisms, and the role of capacitation as seen in eutherian mammals

1996 ◽  
Vol 8 (4) ◽  
pp. 581 ◽  
Author(s):  
RA Harrison
Keyword(s):  
Cell Death ◽  
Reproductive Tract ◽  
Physiological State ◽  
Hormonal Control ◽  
Female Reproductive Tract ◽  
Functional Heterogeneity ◽  
Vitro Fertilization ◽  
Range Of Functions

Capacitation, the process whereby spermatozoa are rendered capable of interacting with and fertilizing the egg, was discovered more than 40 years ago. However, our understanding of it is still far from satisfactory. Several factors conspire to obfuscate studies of capacitation mechanisms: the inherent functional heterogeneity of sperm populations, the range of functions used as parameters of capacitation (whence the endpoint of the process has become conceptually uncertain), and the several profound differences between model in vitro fertilization (IVF) systems and the situation in vivo in the female reproductive tract. Recent investigations in the author's laboratory have shown that bicarbonate/CO2, an essential component for successful IVF, causes rapid changes in lipid architecture of the sperm plasma membrane and slower changes in surface coating. These changes are accompanied by membrane destabilization and cell death. Evidence suggests that bicarbonate's actions are mediated through cyclic nucleotide signalling. Of particular note is the heterogeneity in rate of response to bicarbonate shown by individual cells in the sperm populations. Taken together with other observations, the findings suggest that capacitation is a series of positive destabilizing events that eventually lead to cell death. The 'capacitated' state would then be a window of destabilization within which spermatozoa can undergo a zona-induced acrosome reaction and display hyperactivated motility. Further along the destabilization pathway, spontaneous acrosome reactions would occur before total membrane degeneration. In vivo, capacitation would be a conflict between destabilization and sperm survival. Concentrations of bicarbonate are maintained low in the cauda epididymidis, where sperm survive for long periods, and one may speculate that hormonal control of local bicarbonate/CO2 in oviducal 'storage' sites in the female tract could allow 'safe' sequestering of live spermatozoa until around the time of ovulation; the environment may then change to produce a 'capacitating' effect, whence, due to the inherent functional heterogeneity of the sequestered population, small numbers of capacitated spermatozoa are released sequentially. In this way, a succession of spermatozoa in the correct physiological state may be provided for the freshly ovulated egg.

scholarly journals Cervicovaginal microbiota and women’s health outcomes

2021 ◽  
Vol 42 (2) ◽  
pp. 65
Author(s):  
Ciara J Bryant ◽  
Catherine Burke ◽  
Wilhelmina M Huston
Keyword(s):  
Cell Death ◽  
Lactic Acid ◽  
Preterm Birth ◽  
Reproductive Tract ◽  
Adverse Outcomes ◽  
Female Reproductive Tract ◽  
Microbial Composition ◽  
Future Directions ◽  
Susceptibility To Infection ◽  
Acid Producing Bacteria

The human cervicovaginal microbiome has an important role in the health and homoeostasis of the female reproductive tract. A eubiotic microbiome is typically dominated with lactic acid producing bacteria and is categorised into five community state types. Issues arise when the microbiome becomes dysbiotic, with the microbial composition shifting to contain a greater relative abundance of strict and facultative anaerobes. This shift will lead to several adverse changes in the vaginal environment including compromised epithelial cells, cell death, inflammation, and greater susceptibility to infection. These changes are associated with various adverse outcomes including infections, preterm birth, and infertility. In this review, we discuss how the cervicovaginal microbiome influences these outcomes and possible future directions of treatment and research.

scholarly journals Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12

Open Medicine ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. 151-159
Author(s):  
Wei Zhao ◽  
Yingyan Zhao ◽  
Ling Chen ◽  
Yan Sun ◽  
Sumei Fan
Keyword(s):  
Cell Proliferation ◽  
Uterine Leiomyoma ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Reproductive Tract ◽  
Quantitative Polymerase Chain Reaction ◽  
Female Reproductive Tract ◽  
Cell Counting ◽  
Proliferation And Apoptosis

Abstract Background/aims Uterine leiomyoma (ULM) is a kind of gene-involved benign tumor, which is located in the front of female reproductive tract. It is one of the most common reproductive tract tumors in women, which leads to abnormal menstruation, repeated pregnancy loss, and other serious gynecological diseases. Recently, microRNAs (miRNAs) have attracted much more attention in the process of exploring the molecular mechanisms of tumorigenesis. Furthermore, the deregulated miRNAs had been reported to play important roles in ULM pathology. Methods In this study, we assessed the expression level of microRNA-199a-5p (miR-199a-5p) in human ULM by quantitative polymerase chain reaction. After that cell counting kit 8, colony formation, 5-ethynyl-20-deoxyuridine, flow cytometry, and Western blot analyses were performed to investigate the effects of miR-199a-5p on ULM cell proliferation and apoptosis. Results We confirmed that miR-199a-5p was significantly downregulated in human ULM. The results of function analyses showed that miR-199a-5p inhibited cell proliferation and induced cell apoptosis in vitro. Bioinformatics tool showed oncogene MED12 was one of the target genes of miR-199a-5p, which mediated the effect of miR-199a-5p on the ULM. Conclusion Our results showed that miR-199a-5p functioned as an antitumor factor in human ULM cells. These findings broaden the current findings on the function of miR-199a-5p into the ULM pathogenesis, and miR-199a-5p may serve as a prognosis and therapeutic target for the ULM and its related diseases.

scholarly journals Deletion of Dicer in Somatic Cells of the Female Reproductive Tract Causes Sterility

2008 ◽  
Vol 22 (10) ◽  
pp. 2336-2352 ◽  
Author(s):  
Ankur K. Nagaraja ◽  
Claudia Andreu-Vieyra ◽  
Heather L. Franco ◽  
Lang Ma ◽  
Ruihong Chen ◽  
...  
Keyword(s):  
Target Genes ◽  
Reproductive Tract ◽  
Somatic Cells ◽  
Cell Types ◽  
Female Reproductive Tract ◽  
Conditional Knockout ◽  
Female Sterility ◽  
Small Interfering Rnas ◽  
Conditional Deletion ◽  
And Function

Abstract Dicer is an evolutionarily conserved ribonuclease III that is necessary for microRNA (miRNA) processing and the synthesis of small interfering RNAs from long double-stranded RNA. Although it has been shown that Dicer plays important roles in the mammalian germline and early embryogenesis, the functions of Dicer-dependent pathways in the somatic cells of the female reproductive tract are unknown. Using a transgenic line in which Cre recombinase is driven by the anti-Müllerian hormone receptor type 2 promoter, we conditionally inactivated Dicer1 in the mesenchyme of the developing Müllerian ducts and postnatally in ovarian granulosa cells and mesenchyme-derived cells of the oviducts and uterus. Deletion of Dicer in these cell types results in female sterility and multiple reproductive defects including decreased ovulation rates, compromised oocyte and embryo integrity, prominent bilateral paratubal (oviductal) cysts, and shorter uterine horns. The paratubal cysts act as a reservoir for spermatozoa and oocytes and prevent embryos from transiting the oviductal isthmus and passing the uterotubal junction to enter the uterus for implantation. Deep sequencing of small RNAs in oviduct revealed down-regulation of specific miRNAs in Dicer conditional knockout females compared with wild type. The majority of these differentially expressed miRNAs are predicted to regulate genes important for Müllerian duct differentiation and mesenchyme-derived structures, and several of these putative target genes were significantly up-regulated upon conditional deletion of Dicer1. Thus, our findings reveal diverse and critical roles for Dicer and its miRNA products in the development and function of the female reproductive tract.

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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