Role of tissue kallikrein-related peptidases in cervical mucus remodeling and host defense

2008 ◽  
Vol 389 (12) ◽  
Author(s):  
Julie L.V. Shaw ◽  
Constantina Petraki ◽  
Carole Watson ◽  
Alan Bocking ◽  
Eleftherios P. Diamandis

AbstractHuman tissue kallikrein-related peptidases (KLKs) are 15 hormonally regulated genes on chromosome 19q13.4 encoding secreted serine proteases. Many KLKs are expressed throughout the female reproductive system and found in cervico-vaginal fluid (CVF). Immunohistochemistry was performed to determine KLK localization in the female reproductive system (fallopian tube, endometrium, cervix and vagina tissues). KLK levels were measured in CVF and saliva over the menstrual cycle to study whether KLKs are regulated by hormonal changes during the cycle.In vitrocleavage analysis was performed to establish whether KLKs may play a role in vaginal epithelial desquamation, mucus remodeling or processing of antimicrobial proteins. KLKs were localized in the glandular epithelium of the fallopian tubes and endometrium, the cervical mucus-secreting epithelium and vaginal stratified squamous epithelium. KLK levels peaked in CVF and saliva after ovulation.In vitrocleavage analysis confirmed KLKs 5 and 12 as capable of digesting desmoglein and desmocollin adhesion proteins and cervical mucin proteins 4 and 5B. KLK5 can digest defensin-1α, suggesting it may aid in cervico-vaginal host defense. We provide evidence of potential physiological roles for KLKs in cervico-vaginal physiology: in desquamation of vaginal epithelial cells, remodeling of cervical mucus and processing of antimicrobial proteins.

2017 ◽  
Vol 66 (5) ◽  
pp. 46-55 ◽  
Author(s):  
Pavel P. Yakovlev

The Aim of the study was to assess modern considerations about the role of aromatase P450 enzyme in female reproductive system and the effect of its activity on the protocols of in vitro fertilization (IVF). Materials: foreign and Russian literature data from 1978 to 2016. Methods:review and synthesis of publications has been performed. Conclusions: Ovarian aromatase is the key steroidogenesis enzyme of the female reproductive system. Its activity depends on many factors, both of intraovarian and extragonadal origin. The ovarian follicular response and oocyte quality in IVF may depend on aromatase activity.


2021 ◽  
Vol 69 (6) ◽  
pp. 81-89
Author(s):  
Zoya S. Rumyantseva ◽  
Anna N. Sulima ◽  
Nadezhda I. Volotskaya ◽  
Evgenia Yu. Zyablitskaya ◽  
Sergey S. Anikin ◽  
...  

Hypothesis/Aims of study. One of the problems discussed in the field of obstetrics and gynecology is the combined pathology of the reproductive system. Among the female reproductive system disorders associated with uterine leiomyoma, endometrial pathology prevails in the form of local inflammatory, receptor and hormonal changes. The aim of this study was to evaluate the structural features of the endometrium and its receptivity in patients with uterine leiomyoma, depending on its histological type and localization. Study design, materials and methods. We examined 128 women with leiomyoma manifesting abnormal uterine bleeding, using clinical, instrumental and morphological methods. Results. Combined pathological changes in the endometrium are more characteristic of submucous leiomyoma compared to intramural and subserous leiomyomas. The proliferative activity of endometrial cells in submucous leiomyoma is two or more times higher than in intramural and subserous leiomyoma. In submucous leiomyoma, cell proliferation occurs significantly more often than in other locations of myomatous nodes.


2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Julie L.V. Shaw ◽  
Eleftherios P. Diamandis

AbstractHuman tissue kallikrein-related peptidases (KLK) are a family of 15 genes located on chromosome 19q13.4 that encode secreted serine proteases with trypsin- and/or chymotrypsin-like activity. Relatively large levels of many KLKs are present in human cervico-vaginal fluid (CVF) and in the supernatant of cultured human vaginal epithelial cells. Many KLKs are also hormonally regulated in vaginal epithelial cells, particularly by glucocorticoids and estrogens. The physiological role of KLK in the vagina is currently unknown; however, analysis of the CVF proteome has revealed clues for potential KLK functions in this environment. Here, we detail potential roles for KLKs in cervico-vaginal physiology. First, we suggest that KLKs play a role in the vagina similar to their role in skin physiology: (1) in the desquamation of vaginal epithelial cells, similar to their activity in the desquamation of skin corneocytes; and (2) in their ability to activate antimicrobial proteins in CVF as they do in sweat. Consequently, we hypothesize that dysregulated KLK expression in the vagina could lead to the development of pathological conditions such as desquamative inflammatory vaginitis. Second, we propose that KLKs may play a role in premature rupture of membranes and pre-term birth through their cleavage of fetal membrane extracellular matrix proteins.


Author(s):  
Anna Stejskalová ◽  
Hugo Vankelecom ◽  
Marina Sourouni ◽  
Magdalene Y Ho ◽  
Martin Götte ◽  
...  

Author(s):  
Datu Agasi Mohd Kamal ◽  
Siti Fatimah Ibrahim ◽  
Mohd Helmy Mokhtar

The functions of androgen and connexin in the mammalian female reproductive system are suggested to be related. Previous research has shown that androgen affects connexin expression and localization in the female reproductive system, altering its function. However, no definitive conclusion on their cause-effect relationship has been drawn yet. In addition, a high prevalence of women with polycystic ovary syndrome (PCOS), who are characterized by elevated androgen levels and failure of ovulation, has prompted the studies on the relationship between androgen and connexin in the ovaries. This systematic review aims to investigate the effect of androgen on connexin expression in the mammalian female reproductive system. The literature search was conducted using the MEDLINE, EBSCOhost, and Scopus databases and the following keywords: “androgen” or “testosterone” or “androgen blocker” or “anti-androgen” or “androstenedione” or “dehydroepiandrosterone” or “flutamide AND connexin” or “gap junction” or “cell junction”. We only considered in vitro and in vivo studies that involved treatment by androgen or androgen receptor blockers and measured connexin expression as one of the parameters. Our review showed that the exposure to androgen or androgen blocker affects connexin expression but not its localization in the mammalian ovary. However, it is not clear whether androgen downregulates or upregulates connexin expression. Additionally, it is inconclusive whether the upregulation of connexin positively contributes to the ovarian function.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 821
Author(s):  
Ferheen Abbasi ◽  
Mayo Kodani ◽  
Chihiro Emori ◽  
Daiji Kiyozumi ◽  
Masashi Mori ◽  
...  

There are over 200 genes that are predicted to be solely expressed in the oocyte and ovary, and thousands more that have expression patterns in the female reproductive tract. Unfortunately, many of their physiological functions, such as their roles in oogenesis or fertilization, have yet to be elucidated. Previous knockout (KO) mice studies have proven that many of the genes that were once thought to be essential for fertility are dispensable in vivo. Therefore, it is extremely important to confirm the roles of all genes before spending immense time studying them in vitro. To do this, our laboratory analyzes the functions of ovary and oocyte-enriched genes in vivo through generating CRISPR/Cas9 KO mice and examining their fertility. In this study, we have knocked out three Oosp family genes (Oosp1, Oosp2, and Oosp3) that have expression patterns linked to the female reproductive system and found that the triple KO (TKO) mutant mice generated exhibited decreased prolificacy but were not infertile; thus, these genes may potentially be dispensable for fertility. We also generated Cd160 and Egfl6 KO mice and found these genes are individually dispensable for female fertility. KO mice with no phenotypic data are seldom published, but we believe that this information must be shared to prevent unnecessary experimentation by other laboratories.


1972 ◽  
Vol 70 (2) ◽  
pp. 396-408 ◽  
Author(s):  
K.-D. Schulz ◽  
H. Haarmann ◽  
A. Harland

ABSTRACT The present investigation deals with the oestrogen-sensitivity of the female reproductive system during the neonatal period. Newborn female guinea pigs were used as test animals. At different times after a single subcutaneous injection of a physiological dose of 0.1 μg or an unphysiologically high dose of 10 μg 17β-oestradiol/100 g body weight, the RNA- and protein-synthesis was examined in the hypothalamic region, pituitary, cerebral cortex, liver, adrenal gland, ovary and uterus. With a physiological dose an increase in organ weight, protein content, RNA-and protein-synthesis was found only in the uterus. These alterations turned out to be dose-dependent. In addition to the findings in the uterus an inhibition of the aminoacid incorporation rate occurred in the liver following the injection of the high oestradiol dose. As early as 1 hour after the administration of 0.1 μg 17β-oestradiol an almost 100% increase in uterine protein synthesis was detectable. This result demonstrates a high oestrogen-sensitivity of this organ during the neonatal period. All the other organs of the female reproductive system such as the hypothalamus, pituitary and ovary did not show any oestrogen response. Therefore the functional immaturity of the uterus during post partem life is not the result of a deficient hormone sensitivity but is correlated with the absence of a sufficient hormonal stimulus at this time. The investigation on the effects of actinomycin resulted in different reactions in the uterus and liver. In contrast to the liver a paradoxical actinomycin effect was found in the uterus after treatment with actinomycin alone. This effect is characterized by a small inhibition of RNA-synthesis and a 50% increase in protein synthesis. The treatment of the newborn test animals with actinomycin and 17β-oestradiol together abolished the oestrogen-induced stimulation of the uterine RNA-and protein-synthesis. Consequently, the effect of oestrogens during the neonatal period is also connected with the formation of new proteins via an increased DNA-directed RNA-synthesis.


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