ijms-logo

Journal Browser

Journal Browser

Special Issue "Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2019).

Special Issue Editor

Prof. Dr. Seung-Yup Ku
Website
Guest Editor
Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yonkeun-dong, Chongno-gu, Seoul 110-744, South Korea
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Reproduction is a very critical scientific phenomenon, tied to the origin of mankind. Successful or failed pregnancy, menstrual dysfunction, and the tumorigenesis of female reproductive organs currently offer numerous challenges to meet clinically unmet needs and often require advanced therapeutic strategies.

There has been exciting progress in understanding the molecular pathophysiology of various uterine and ovarian diseases and dysfunction in recent years. Genetic or epigenetic alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for those diseases and dysfunction. To date, specific biomarkers as well as genetic or epigenetic alterations have been identified.

This Special Issue of IJMS searches for answers to some of the above mentioned questions in an attempt to provide reproductive biomedical scientists and clinicians with novel answers that should lead to a better understanding of such prevalent and serious universal diseases and dysfunction. Studies using animal or cell culture models to investigate the molecular pathophysiology of uterine and ovarian diseases and dysfunction will be published. This issue will also cover studies and reports on patients and clinical samples, enlightening novel insights into underlying pathophysiology/pathogenesis, or new aspects that may impact the progressive development of clinical therapy.

IJMS looks forward to receiving excellent contributions from all types of investigators of female reproductive tract dysfunction and diseases.

Prof. Dr. Seung-Yup Ku
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • uterine tumor
  • ovarian tumor
  • hormonal dysfunction
  • polycystic ovary syndrome
  • endometriosis
  • menopause
  • infertility
  • pregnancy
  • abortion
  • assisted reproduction
  • pluripotent stem cell
  • tissue engineering

Published Papers (14 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Expression of Matrix Metalloproteinases and Their Inhibitors in Endometrium: High Levels in Endometriotic Lesions
Int. J. Mol. Sci. 2020, 21(8), 2840; https://doi.org/10.3390/ijms21082840 - 18 Apr 2020
Abstract
Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions [...] Read more.
Endometriosis is a condition defined as presence of endometrium outside of the uterine cavity. These endometrial cells are able to attach and invade the peritoneum or ovary, thus forming respectively the deep infiltrating endometriosis (DIE) and the ovarian endometrioma (OMA), the ectopic lesions feature of this pathology. Endometriotic cells display high invasiveness and share some features of malignancy with cancer cells. Indeed, the tissue remodeling underlining lesion formation is achieved by matrix metalloproteinases (MMPs) and their inhibitors. Therefore, these molecules are believed to play a key role in development and pathogenesis of endometriosis. This study investigated the molecular profile of metalloproteinases and their inhibitors in healthy (n = 15) and eutopic endometrium (n = 19) in OMA (n = 10) and DIE (n = 9); moreover, we firstly validated the most reliable housekeeping genes allowing accurate gene expression analysis in these tissues. Gene expression, Western blot, and immunofluorescence analysis of MMP2, MMP3, and MMP10 and their tissue inhibitors TIMP1 and TIMP2 demonstrated that these enzymes are finely tuned in these tissues. In OMA lesions, all the investigated MMPs and their inhibitors were significantly increased, while DIE expressed high levels of MMP3. Finally, in vitro TNFα treatment induced a significant upregulation of MMP3, MMP10, and TIMP2 in both healthy and eutopic endometrial stromal cells. This study, shedding light on MMP and TIMP expression in endometriosis, confirms that these molecules are altered both in eutopic endometrium and endometriotic lesions. Although further studies are needed, these data may help in understanding the molecular mechanisms involved in the extracellular matrix remodeling, a crucial process for the endometrial physiology. Full article
Show Figures

Figure 1

Open AccessArticle
Effects of Natural Progesterone and Synthetic Progestin on Germ Layer Gene Expression in a Human Embryoid Body Model
Int. J. Mol. Sci. 2020, 21(3), 769; https://doi.org/10.3390/ijms21030769 - 24 Jan 2020
Cited by 1
Abstract
Natural progesterone and synthetic progestin are widely used for the treatment of threatened abortion or in in vitro fertilization (IVF) cycles. This in vitro study aimed to assess whether the treatment with natural progesterone or synthetic progestin influences the germ layer gene expression [...] Read more.
Natural progesterone and synthetic progestin are widely used for the treatment of threatened abortion or in in vitro fertilization (IVF) cycles. This in vitro study aimed to assess whether the treatment with natural progesterone or synthetic progestin influences the germ layer gene expression on the early human embryonic development using human embryonic stem cells (hESCs)-derived embryoid bodies (hEBs) as a surrogate of early stage human embryonic development. Human EBs derived from hESCs were cultured for nine days, and were treated with natural progesterone (P4) or synthetic progestin, medroxyprogesterone acetate (MPA) at 10–7 M for five days. To reverse the effects of treatment, mifepristone (RU486) as progesterone antagonist was added to the hEBs for four days starting one day after the initiation of treatment. Mouse blastocysts (mBLs) were cultured in vitro for 24 h, and P4 or MPA at 10−7 M was treated for an additional 24 h. The treated embryos were further transferred onto in vitro cultured endometrial cells to evaluate chorionic gonadotropin (CG) expression. To analyze the effects of P4 or MPA, the expression of differentiation genes representing the three germ layers was investigated, GATA-binding factor 4 (GATA4), α-fetoprotein (AFP), hepatocyte nuclear factor (HNF)-3β, hepatocyte nuclear factor (HNF)-4α (endoderm), Brachyury, cardiac actin (cACT) (mesoderm), and Nestin (ectoderm), using quantitative reverse transcription PCR (qRT-PCR) and immunostaining. Significantly lower expressions of HNF-3β, HNF-4α, Brachyury, and Nestin were observed in MPA-treated hEBs (all p < 0.05), which was negated by RU486 treatment. This inhibitory effect of MPA was also observed in mouse embryos. Conclusively, the effects of natural progesterone and synthetic progestin may differ in the germ layer gene expression in the hEB model, which suggests that caution is necessary in the use of progestogen. Full article
Show Figures

Figure 1

Open AccessArticle
Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women
Int. J. Mol. Sci. 2020, 21(1), 295; https://doi.org/10.3390/ijms21010295 - 31 Dec 2019
Abstract
Sirtuins are a family of deacetylases that modify structural proteins, metabolic enzymes, and histones to change cellular protein localization and function. In mammals, there are seven sirtuins involved in processes like oxidative stress or metabolic homeostasis associated with aging, degeneration or cancer. We [...] Read more.
Sirtuins are a family of deacetylases that modify structural proteins, metabolic enzymes, and histones to change cellular protein localization and function. In mammals, there are seven sirtuins involved in processes like oxidative stress or metabolic homeostasis associated with aging, degeneration or cancer. We studied gene expression of sirtuins by qRT-PCR in human mural granulosa-lutein cells (hGL) from IVF patients in different infertility diagnostic groups and in oocyte donors (OD; control group). Study 1: sirtuins genes’ expression levels and correlations with age and IVF parameters in women with no ovarian factor. We found significantly higher expression levels of SIRT1, SIRT2 and SIRT5 in patients ≥40 years old than in OD and in women between 27 and 39 years old with tubal or male factor, and no ovarian factor (NOF). Only SIRT2, SIRT5 and SIRT7 expression correlated with age. Study 2: sirtuin genes’ expression in women poor responders (PR), endometriosis (EM) and polycystic ovarian syndrome. Compared to NOF controls, we found higher SIRT2 gene expression in all diagnostic groups while SIRT3, SIRT5, SIRT6 and SIRT7 expression were higher only in PR. Related to clinical parameters SIRT1, SIRT6 and SIRT7 correlate positively with FSH and LH doses administered in EM patients. The number of mature oocytes retrieved in PR is positively correlated with the expression levels of SIRT3, SIRT4 and SIRT5. These data suggest that cellular physiopathology in PR’s follicle may be associated with cumulative DNA damage, indicating that further studies are necessary. Full article
Show Figures

Graphical abstract

Open AccessArticle
Endometrial Stromal Cells Circulate in the Bloodstream of Women with Endometriosis: A Pilot Study
Int. J. Mol. Sci. 2019, 20(15), 3740; https://doi.org/10.3390/ijms20153740 - 31 Jul 2019
Cited by 3
Abstract
Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; [...] Read more.
Endometriosis is characterized by the presence of endometrial tissue outside the uterus. While endometriotic tissue is commonly localized in the pelvic cavity, it can also be found in distant sites, including the brain. The origin and pathophysiology of tissue migration is poorly understood; retrograde menstruation is thought to be the cause, although the presence of endometrium at distant sites is not explained by this hypothesis. To determine whether dissemination occurs via the bloodstream in women with endometriosis, we analyzed circulating blood for the presence of endometrial cells. Circulating endometrial stromal cells were identified only in women with endometriosis but not in controls, while endometrial epithelial cells were not identified in the circulation of either group. Our results support the hypothesis that endometrial stromal cells may migrate through circulation and promote the pathophysiology of endometriosis. The detection of these cells in circulation creates avenues for the development of less invasive diagnostic tools for the disease, and opens possibilities for further study of the origin of endometriosis. Full article
Show Figures

Figure 1

Open AccessArticle
RUNX3 Promotes the Tumorigenic Phenotype in KGN, a Human Granulosa Cell Tumor-Derived Cell Line
Int. J. Mol. Sci. 2019, 20(14), 3471; https://doi.org/10.3390/ijms20143471 - 15 Jul 2019
Cited by 3
Abstract
Granulosa cell tumors of the ovary (GCT) are the predominant type of ovarian sex cord/stromal tumor. Although prognosis is generally favorable, the outcome for advanced and recurrent GCT is poor. A better understanding of the molecular pathogenesis of GCT is critical to developing [...] Read more.
Granulosa cell tumors of the ovary (GCT) are the predominant type of ovarian sex cord/stromal tumor. Although prognosis is generally favorable, the outcome for advanced and recurrent GCT is poor. A better understanding of the molecular pathogenesis of GCT is critical to developing effective therapeutic strategies. Here we have examined the potential role of the runt-related transcription factor RUNX3. There are only two GCT cell lines available. While RUNX3 is silenced in the GCT cell line KGN cells, it is highly expressed in another GCT cell line, COV434 cells. Re-expression of RUNX3 promotes proliferation, anchorage-independent growth, and motility in KGN cells in vitro and tumor formation in mice in vivo. Furthermore, expression of a dominant negative form of RUNX3 decreases proliferation of COV434 cells. To address a potential mechanism of action, we examined expression of cyclin D2 and the CDK inhibitor p27Kip1, two cell cycle regulators known to be critical determinants of GCT cell proliferation. We found that RUNX3 upregulates the expression of cyclin D2 at the mRNA and protein level, and decreases the level of the p27Kip1 protein, but not p27Kip1 mRNA. In conclusion, we demonstrate that RUNX proteins are expressed in GCT cell lines and human GCT specimens, albeit at variable levels, and RUNX3 may play an oncogenic role in a subset of GCTs. Full article
Show Figures

Figure 1

Open AccessArticle
Comparison between Slow Freezing and Vitrification for Human Ovarian Tissue Cryopreservation and Xenotransplantation
Int. J. Mol. Sci. 2019, 20(13), 3346; https://doi.org/10.3390/ijms20133346 - 08 Jul 2019
Cited by 7
Abstract
Two methods for the cryopreservation of human ovarian tissue were compared using a xenotransplantation model to establish a safe and effective cryopreservation method. Ovarian tissues were obtained from women who underwent benign ovarian surgery in the gynecology research unit of a university hospital. [...] Read more.
Two methods for the cryopreservation of human ovarian tissue were compared using a xenotransplantation model to establish a safe and effective cryopreservation method. Ovarian tissues were obtained from women who underwent benign ovarian surgery in the gynecology research unit of a university hospital. The tissues were transplanted into 112 ovariectomized female severe combined immunodeficient mice 4 weeks after slow freezing or vitrification cryopreservation. Tissues were retrieved 4 weeks later. Primordial follicular counts decreased after cryopreservation and xenotransplantation, and were significantly higher in the slow freezing group than in the vitrification group (p < 0.001). Immunohistochemistry and TUNEL assay showed that the Ki-67 and CD31 markers of follicular proliferation and angiogenesis were higher in the slow freezing group (p < 0.001 and p = 0.006, respectively) and DNA damage was greater in the vitrification group (p < 0.001). Western blotting showed that vitrification increased cellular apoptosis. Anti-Müllerian hormone expression was low in transplanted samples subjected to both cryopreservation techniques. Electron microscopy revealed primordial follicle deformation in the vitrification group. Slow freezing for ovarian tissue cryopreservation is superior to vitrification in terms of follicle survival and growth after xenotransplantation. These results will be useful for fertility preservation in female cancer patients. Full article
Show Figures

Figure 1

Open AccessArticle
Protein–Protein Interaction Network Analysis Reveals Several Diseases Highly Associated with Polycystic Ovarian Syndrome
Int. J. Mol. Sci. 2019, 20(12), 2959; https://doi.org/10.3390/ijms20122959 - 18 Jun 2019
Cited by 4
Abstract
Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein–protein [...] Read more.
Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein–protein interaction (PPI) network analysis are useful in understanding the disease association in detail. This study utilized this approach to deepen the knowledge on the association between PCOS and other diseases. A PPI network for PCOS was constructed using PCOS-related proteins (PCOSrp) obtained from PCOSBase. MCODE was used to identify highly connected regions in the PCOS network, known as subnetworks. These subnetworks represent protein families, where their molecular information is used to explain the association between PCOS and other diseases. Fisher’s exact test and comorbidity data were used to identify PCOS–disease subnetworks. Pathway enrichment analysis was performed on the PCOS–disease subnetworks to identify significant pathways that are highly involved in the PCOS–disease associations. Migraine, schizophrenia, depressive disorder, obesity, and hypertension, along with twelve other diseases, were identified to be highly associated with PCOS. The identification of significant pathways, such as ribosome biogenesis, antigen processing and presentation, and mitophagy, suggest their involvement in the association between PCOS and migraine, schizophrenia, and hypertension. Full article
Show Figures

Graphical abstract

Open AccessArticle
MiR-150-5p May Contribute to Pathogenesis of Human Leiomyoma via Regulation of the Akt/p27Kip1 Pathway In Vitro
Int. J. Mol. Sci. 2019, 20(11), 2684; https://doi.org/10.3390/ijms20112684 - 31 May 2019
Cited by 3
Abstract
Uterine leiomyoma is found in ~50–80% of women of a reproductive age and is the most common reason for hysterectomy. Recently, posttranscriptional gene silencing by microRNAs (miRs) has been reported as a mechanism for regulating gene expression stability in the pathogenesis of uterine [...] Read more.
Uterine leiomyoma is found in ~50–80% of women of a reproductive age and is the most common reason for hysterectomy. Recently, posttranscriptional gene silencing by microRNAs (miRs) has been reported as a mechanism for regulating gene expression stability in the pathogenesis of uterine leiomyomas. In this study, miR microarray analysis of leiomyomas and paired myometrial tissue revealed numerous aberrantly expressed miRs, including miR-150. In functional assays, transfection with miR-150 mimic resulted in decreased migration and fibrosis, implying an inhibition of leiomyoma growth. To identify the target genes of miR-150 in leiomyoma, gene set analysis and network analysis were performed. To overcome the limitations of in silico analysis, changes in expression levels of hallmark genes in leiomyoma after transfection with a miR-150 mimic were also evaluated using qRT-PCR. As a result, the Akt/p27Kip1 pathway was presumed to be one of the target pathways of miR-150. After transfecting cultured leiomyoma cells with the miR-150 mimic, expression levels of its target gene Akt decreased, whereas those of p27Kip1 increased significantly. Our results suggest that miR-150 affects the cell cycle regulation in uterine leiomyoma through the Akt/p27Kip1 pathway. Full article
Show Figures

Graphical abstract

Open AccessArticle
Expression of Transcripts in Marmoset Oocytes Retrieved during Follicle Isolation Without Gonadotropin Induction
Int. J. Mol. Sci. 2019, 20(5), 1133; https://doi.org/10.3390/ijms20051133 - 06 Mar 2019
Cited by 2
Abstract
The in vitro maturation of oocytes is frequently used as an assisted reproductive technique (ART), and has been successfully established in humans and rodents. To overcome the limitations of ART, novel procedures for the in vitro maturation of early follicles are emerging. During [...] Read more.
The in vitro maturation of oocytes is frequently used as an assisted reproductive technique (ART), and has been successfully established in humans and rodents. To overcome the limitations of ART, novel procedures for the in vitro maturation of early follicles are emerging. During the follicle isolation procedure, the unintended rupture of each follicle leads to a release of extra oocytes. Such oocytes, which are obtained during follicle isolation from marmosets, can be used for early maturation studies. Marmoset (Callithrix jacchus), which is classified as a new-world monkey, is a novel model that has been employed in reproductive biomedical research, as its reproductive physiology is similar to that of humans in several aspects. The ovaries of female marmosets were collected, and the excess oocytes present during follicle isolation were retrieved without pre-gonadotropin induction. Each oocyte was matured in vitro for 48 h in the presence of various concentrations of human chorionic gonadotropin (hCG) and epidermal growth factor (EGF), and the maturity of oocytes and optimal maturation conditions were evaluated. Each oocyte was individually reverse-transcribed, and the expression of mRNAs and microRNAs (miRs) were analyzed. Concentrations of hCG significantly affected the maturation rate of oocytes [the number of metaphase II (MII) oocytes]. The expression of BMP15 and ZP1 was highest when the oocytes were matured using 100 IU/L of hCG without pre-treatment with gonadotropins, and that of Cja-mir-27a was highest when cultured with follicle stimulating hormone. These results suggest that these up-regulated miRs affect the maturation of oocytes. Interactions with other protein networks were analyzed, and a strong association of BMP15 and ZP1 with sperm binding receptor (ACR), anti-Müllerian hormone (AMH), and AMH receptor was demonstrated, which is related to the proliferation of granulosa cells. Collectively, on the basis of these results, the authors propose optimal maturation conditions of excess oocytes of marmoset without in vivo gonadotropin treatment, and demonstrated the roles of miRs in early oocyte maturation at the single-cell level in marmosets. Full article
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Ovarian Follicle Depletion Induced by Chemotherapy and the Investigational Stages of Potential Fertility-Protective Treatments—A Review
Int. J. Mol. Sci. 2019, 20(19), 4720; https://doi.org/10.3390/ijms20194720 - 23 Sep 2019
Cited by 2
Abstract
Ovarian follicle pool depletion, infertility, and premature menopause are all known sequelae of cancer treatment that negatively impact the quality of life of young cancer survivors. The mechanisms involved in this undesired iatrogenic ovarian damage have been intensively studied, but many of them [...] Read more.
Ovarian follicle pool depletion, infertility, and premature menopause are all known sequelae of cancer treatment that negatively impact the quality of life of young cancer survivors. The mechanisms involved in this undesired iatrogenic ovarian damage have been intensively studied, but many of them remain unclear. Several chemotherapeutic drugs have been shown to induce direct and indirect DNA-damage and/or cellular stress, which are often followed by apoptosis and/or autophagy. Damage to the ovarian micro-vessel network induced by chemotherapeutic agents also seems to contribute to ovarian dysfunction. Another proposed mechanism behind ovarian follicle pool depletion is the overactivation of primordial follicles from the quiescent pool; however, current experimental data are inconsistent regarding these effects. There is great interest in characterizing the mechanisms involved in ovarian damage because this might lead to the identification of potentially protective substances as possible future therapeutics. Research in this field is still at an experimental stage, and further investigations are needed to develop effective and individualized treatments for clinical application. This review provides an overview of the current knowledge and the proposed hypothesis behind chemotherapy-induced ovarian damage, as well as current knowledge on possible co-treatments that might protect the ovary and the follicles from such damages. Full article
Show Figures

Figure 1

Open AccessReview
Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?
Int. J. Mol. Sci. 2019, 20(15), 3822; https://doi.org/10.3390/ijms20153822 - 05 Aug 2019
Cited by 24
Abstract
In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily [...] Read more.
In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily through their cognate receptors to set off cascades of signaling pathways and enact large-scale gene expression programs. In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance. This hormone imbalance leads to heightened inflammation and may also increase the pelvic pain of the disease and decrease endometrial receptivity to embryo implantation. This review focuses on the molecular mechanisms governing progesterone and estrogen signaling supporting endometrial function and how they become dysregulated in endometriosis. Understanding how these mechanisms contribute to the pelvic pain and infertility associated with endometriosis will open new avenues of targeted medical therapies to give relief to the millions of women suffering its effects. Full article
Show Figures

Graphical abstract

Open AccessReview
Bacterial Colonization of the Female Upper Genital Tract
Int. J. Mol. Sci. 2019, 20(14), 3405; https://doi.org/10.3390/ijms20143405 - 11 Jul 2019
Cited by 10
Abstract
Bacteria colonize most of the human body, and the female genital tract is not an exception. While the existence of a vaginal microbiota has been well established, the upper genital tract has been considered a sterile environment, with a general assumption that bacterial [...] Read more.
Bacteria colonize most of the human body, and the female genital tract is not an exception. While the existence of a vaginal microbiota has been well established, the upper genital tract has been considered a sterile environment, with a general assumption that bacterial presence is associated with adverse clinical manifestation. However, recent metagenomic studies identified specific patterns of microbiota colonizing the uterus, fallopian tubes, ovaries, and placenta. These results need confirmation and further investigations since the data are only scarce. Bacterial colonization of these sites appears different from the vaginal one, despite evidence that vaginal bacteria could ascend to the upper genital tract through the cervix. Are these bacteria only commensal or do they play a role in the physiology of the female upper genital tract? Which are the genera that may have a negative and a positive impact on the female reproductive function? The aim of this review is to critically present all available data on upper genital tract microbiota and discuss its role in human reproduction, ranging from the technical aspects of these types of analyses to the description of specific bacterial genera. Although still very limited, research focusing on genital colonization of bacteria other than the vaginal milieu might bring novel insights into physiopathology of human reproduction. Full article
Show Figures

Figure 1

Open AccessReview
The Impact of Iron Overload and Ferroptosis on Reproductive Disorders in Humans: Implications for Preeclampsia
Int. J. Mol. Sci. 2019, 20(13), 3283; https://doi.org/10.3390/ijms20133283 - 04 Jul 2019
Cited by 3
Abstract
Iron is an essential element for the survival of most organisms, including humans. Demand for iron increases significantly during pregnancy to support growth and development of the fetus. Paradoxically, epidemiologic studies have shown that excessive iron intake and/or high iron status can be [...] Read more.
Iron is an essential element for the survival of most organisms, including humans. Demand for iron increases significantly during pregnancy to support growth and development of the fetus. Paradoxically, epidemiologic studies have shown that excessive iron intake and/or high iron status can be detrimental to pregnancy and is associated with reproductive disorders ranging from endometriosis to preeclampsia. Reproductive complications resulting from iron deficiency have been reviewed elsewhere. Here, we focus on reproductive disorders associated with iron overload and the contribution of ferroptosis—programmed cell death mediated by iron-dependent lipid peroxidation within cell membranes—using preeclampsia as a model system. We propose that the clinical expressions of many reproductive disorders and pregnancy complications may be due to an underlying ferroptopathy (elemental iron-associated disease), characterized by a dysregulation in iron homeostasis leading to excessive ferroptosis. Full article
Show Figures

Figure 1

Open AccessReview
Animal Models for Human Polycystic Ovary Syndrome (PCOS) Focused on the Use of Indirect Hormonal Perturbations: A Review of the Literature
Int. J. Mol. Sci. 2019, 20(11), 2720; https://doi.org/10.3390/ijms20112720 - 03 Jun 2019
Cited by 3
Abstract
Hormonal disturbances, such as hyperandrogenism, are considered important for developing polycystic ovary syndrome (PCOS) in humans. Accordingly, directly hormone-regulated animal models are widely used for studying PCOS, as they replicate several key PCOS features. However, the pathogenesis and treatment of PCOS are still [...] Read more.
Hormonal disturbances, such as hyperandrogenism, are considered important for developing polycystic ovary syndrome (PCOS) in humans. Accordingly, directly hormone-regulated animal models are widely used for studying PCOS, as they replicate several key PCOS features. However, the pathogenesis and treatment of PCOS are still unclear. In this review, we aimed to investigate animal PCOS models and PCOS-like phenotypes in animal experiments without direct hormonal interventions and determine the underlying mechanisms for a better understanding of PCOS. We summarized animal PCOS models that used indirect hormonal interventions and suggested or discussed pathogenesis of PCOS-like features in animals and PCOS-like phenotypes generated in other animals. We presented integrated physiological insights and shared cellular pathways underlying the pathogenesis of PCOS in reviewed animal models. Our review indicates that the hormonal and metabolic changes could be due to molecular dysregulations, such as upregulated PI3K-Akt and extracellular signal-regulated kinase (ERK) signalling, that potentially cause PCOS-like phenotypes in the animal models. This review will be helpful for considering alternative animal PCOS models to determine the cellular/molecular mechanisms underlying PCOS symptoms. The efforts to determine the specific cellular mechanisms of PCOS will contribute to novel treatments and control methods for this complex syndrome. Full article
Show Figures

Figure 1

Back to TopTop