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Advanced Research on Reproductive System Disease 2022
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Advanced Research on Reproductive System Disease 2022

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 (20 December 2022) | Viewed by 14369

Special Issue Editor

Dr. Anna Perri

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University “Magna Graecia” Catanzaro, 88100 Catanzaro, Italy
Interests: cancer endocrinology; molecular biology; signal transduction; p75NTR-signaling; apoptosis; autophagy; EMT; renal and peritoneal fibrosis; inflammation; biological activity of natural compounds in cancer and chronic diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Reproductive related diseases include a broad range of disorders, which incidence is increased in recent decades in both sexes, because of increasing risk factors, as obesity, sexually transmitted infections, environmental pollution and so on. A growing literature focused on the molecular mechanisms underlined to the reproductive system disorders, and different approaches have been developed to identify new early biomarkers disease, as well as news promising therapeutic targets. In this scenario, a highly promising tool is represented by the“-omic” technology. Recently it has been demonstrated that male and female gonadal cancers can be distinct not only in terms of histology but also in genomics, epigenomics and transcriptomics. Moreover, recent studies shown that epigenetic changes (as those environmental pollution-induced) are an important component of gametogenesis and related reproductive system diseases, including cancers. This innovative approach is crucial to developing new drugs to overcome the chemoresistance. In addition, understanding the role of post-transcriptional gene regulation in reproduction will help to clarify the causes of reproductive failure, providing methods and targets for the treatment of infertility, which represents well known consequence of congenital and aquired reproductive system disorders. Finally, in recent years the researchers have conducted in vivo and in vivo studies to investigate the molecular mechanism by which some natural products may be applied as new potential adiuvant therapeutic tool.

This Special Issue of the International Journal of Molecular Sciences focuses on the Reproductive System Disease research field and welcomes both original research articles and review papers that deal with the molecular mechanisms underlying the gonadal and sexual dysfunction and new advanced diagnostic and therapeutic approaches in the treatment of the above-reported disorders and of infertility.

Dr. Anna Perri
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 submissions that pass pre-check are 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

  • male reproduction
  • female reproduction
  • omic technology
  • infertility
  • cancer
  • genital tract infection
  • molecular mechanisms

Published Papers (5 papers)

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Research

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28 pages, 1684 KiB  
Article
The Association between Clusterin Sialylation Degree and Levels of Oxidative–Antioxidant Balance Markers in Seminal Plasmas and Blood Sera of Male Partners with Abnormal Sperm Parameters
by Ewa Janiszewska, Izabela Kokot, Agnieszka Kmieciak, Zuzanna Stelmasiak, Iwona Gilowska, Ricardo Faundez and Ewa Maria Kratz
Int. J. Mol. Sci. 2022, 23(18), 10598; https://doi.org/10.3390/ijms231810598 - 13 Sep 2022
Cited by 5 | Viewed by 1864
Abstract
Nearly 30% of infertility cases are caused by male factor. This study aimed at checking the associations between the sialylation degree of glycoprotein clusterin (CLU) and levels of oxidative–antioxidant balance markers in infertile men. Using lectin-ELISA with biotinylated lectins specific to α2,6-linked ( [...] Read more.
Nearly 30% of infertility cases are caused by male factor. This study aimed at checking the associations between the sialylation degree of glycoprotein clusterin (CLU) and levels of oxidative–antioxidant balance markers in infertile men. Using lectin-ELISA with biotinylated lectins specific to α2,6-linked (Sambucus nigra agglutinin, SNA) and α2,3-linked (Maackia amurensis agglutinin, MAA) sialic acid (SA), the CLU sialylation in 132 seminal plasmas (SP) and 91 blood sera (BS) were analyzed. Oxidative–antioxidant status was measured by determining Sirtuin-3 (SIRT3), Sirtuin-5 (SIRT5), total antioxidant status (TAS), and ferric reducing antioxidant power (FRAP) levels. We indicate that multiple sperm disorders are associated with decreased expression of MAA-reactive SA in SP. Decreased SP SIRT3 concentrations may be associated with teratozoospermia and oligoasthenoteratozoospermia. ROC curve and cluster analysis revealed that SP relative reactivity of CLU glycans with MAA, the value of MAA/SNA ratio, and SIRT3 and SIRT5 concentrations may constitute an additional set of markers differentiating infertile oligoasthenoteratozoospermic patients (OAT) from normozoospermic (N), asthenoteratozoospermic (AT) and teratozoospermic (T). The multinomial logistic regression analysis confirmed the potential utility of SIRT3 determinations for differentiation between N and OAT groups as well as between N and T groups for SIRT3 and SIRT5. For BS, based on ROC curve and cluster analysis, relative reactivities of CLU glycans with SNA, MAA, SIRT3 and FRAP concentrations may be useful in the differentiation of normozoospermic patients from those with sperm disorders. The multinomial logistic regression analysis showed that the SNA relative reactivity with CLU glycans significantly differentiated the N group from AT, OAT and T groups, and FRAP concentrations significantly differed between N and AT groups, which additionally confirms the potential utility of these biomarkers in the differentiation of infertile patients with abnormal sperm parameters. The knowledge about associations between examined parameters may also influence future research aimed at seeking new male infertility therapies. Full article
(This article belongs to the Special Issue Advanced Research on Reproductive System Disease 2022)
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18 pages, 1321 KiB  
Article
Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors’ Dysfunction
by Tomasz Jasiński, Łukasz Zdrojkowski, Graça Ferreira-Dias, Ewa Kautz, Edyta Juszczuk-Kubiak and Małgorzata Domino
Int. J. Mol. Sci. 2022, 23(13), 7360; https://doi.org/10.3390/ijms23137360 - 01 Jul 2022
Cited by 4 | Viewed by 1373
Abstract
Endometrosis is a frequently occurring disease decreasing mares’ fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their [...] Read more.
Endometrosis is a frequently occurring disease decreasing mares’ fertility. Thus, it is an important disease of the endometrium associated with epithelial and stromal cell alterations, endometrium gland degeneration and periglandular fibrosis. Multiple degenerative changes are found in uterine mucosa, the endometrium. However, their pathogenesis is not well known. It is thought that nuclear factor-κB (NF-κB), a cell metabolism regulator, and its activation pathways take part in it. The transcription of the profibrotic pathway genes of the NF-κB in fibrotic endometria differed between the follicular (FLP) and mid-luteal (MLP) phases of the estrous cycle, as well as with fibrosis progression. This study aimed to investigate the transcription of genes of estrogen (ESR1, ESR2) and progesterone receptors (PGR) in equine endometria to find relationships between the endocrine environment, NF-κB-pathway, and fibrosis. Endometrial samples (n = 100), collected in FLP or MLP, were classified histologically, and examined using quantitative PCR. The phase of the cycle was determined through the evaluation of ovarian structures and hormone levels (estradiol, progesterone) in serum. The transcription of ESR1, ESR2, and PGR decreased with the severity of endometrial fibrosis and degeneration of the endometrium. Moreover, differences in the transcription of ESR1, ESR2, and PGR were noted between FLP and MLP in the specific categories and histopathological type of equine endometrosis. In FLP and MLP, specific moderate and strong correlations between ESR1, ESR2, PGR and genes of the NF-κB pathway were evidenced. The transcription of endometrial steroid receptors can be subjected to dysregulation with the degree of equine endometrosis, especially in both destructive types of endometrosis, and mediated by the canonical NF-κB pathway depending on the estrous cycle phase. Full article
(This article belongs to the Special Issue Advanced Research on Reproductive System Disease 2022)
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Review

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17 pages, 1409 KiB  
Review
Female Reproductive Aging and Oxidative Stress: Mesenchymal Stem Cell Conditioned Medium as a Promising Antioxidant
by Kihae Ra, Se Chang Park and Byeong Chun Lee
Int. J. Mol. Sci. 2023, 24(5), 5053; https://doi.org/10.3390/ijms24055053 - 06 Mar 2023
Cited by 11 | Viewed by 2852
Abstract
The recent tendency to delay pregnancy has increased the incidence of age-related infertility, as female reproductive competence decreases with aging. Along with aging, a lowered capacity of antioxidant defense causes a loss of normal function in the ovaries and uterus due to oxidative [...] Read more.
The recent tendency to delay pregnancy has increased the incidence of age-related infertility, as female reproductive competence decreases with aging. Along with aging, a lowered capacity of antioxidant defense causes a loss of normal function in the ovaries and uterus due to oxidative damage. Therefore, advancements have been made in assisted reproduction to resolve infertility caused by reproductive aging and oxidative stress, following an emphasis on their use. The application of mesenchymal stem cells (MSCs) with intensive antioxidative properties has been extensively validated as a regenerative therapy, and proceeding from original cell therapy, the therapeutic effects of stem cell conditioned medium (CM) containing paracrine factors secreted during cell culture have been reported to be as effective as that of direct treatment of source cells. In this review, we summarized the current understanding of female reproductive aging and oxidative stress and present MSC-CM, which could be developed as a promising antioxidant intervention for assisted reproductive technology. Full article
(This article belongs to the Special Issue Advanced Research on Reproductive System Disease 2022)
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20 pages, 353 KiB  
Review
Commonalities and Disparities between Endometriosis and Chronic Endometritis: Therapeutic Potential of Novel Antibiotic Treatment Strategy against Ectopic Endometrium
by Kotaro Kitaya and Tadahiro Yasuo
Int. J. Mol. Sci. 2023, 24(3), 2059; https://doi.org/10.3390/ijms24032059 - 20 Jan 2023
Cited by 10 | Viewed by 3527
Abstract
Chronic endometritis (CE) is a local mucosal inflammatory disorder of the uterine lining, which is histopathologically recognized as the unusual infiltration of CD138(+) plasmacytes into the endometrial stromal compartment. Accumulating body of research documented that CE is associated with female infertility and several [...] Read more.
Chronic endometritis (CE) is a local mucosal inflammatory disorder of the uterine lining, which is histopathologically recognized as the unusual infiltration of CD138(+) plasmacytes into the endometrial stromal compartment. Accumulating body of research documented that CE is associated with female infertility and several obstetric/neonatal complications. The major cause of CE is thought to be intrauterine infection represented by common bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus, and Staphylococcus), Mycoplasma/Ureaplasma, and Mycobacterium. Additionally, local dysbiosis in the female reproductive tract may be involved in the onset and development of CE. Antibiotic treatments against these microorganisms are effective in the elimination of endometrial stromal plasmacytes in the affected patients. Meanwhile, endometriosis is a common female reproductive tract disease characterized by endometriotic tissues (ectopic endometrium) growing outside the uterus and potentially causes chronic pelvic symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), infertility, and ovarian cancers. Endometriosis involves endocrinological, genetic, and epigenetic factors in its etiology and pathogenesis. Recent studies focus on immunological, inflammatory, and infectious aspects of endometriosis and demonstrate several common characteristics between endometriosis and CE. This review aimed to better understand the immunological and microbial backgrounds underlying endometriosis and CE and look into the therapeutic potential of the novel antibiotic treatment strategy against endometriosis in light of endometrial infectious disease. Full article
(This article belongs to the Special Issue Advanced Research on Reproductive System Disease 2022)
33 pages, 2167 KiB  
Review
Impact of Nanoparticles on Male Fertility: What Do We Really Know? A Systematic Review
by Jean-Philippe Klein, Lionel Mery, Delphine Boudard, Célia Ravel, Michèle Cottier and Dimitrios Bitounis
Int. J. Mol. Sci. 2023, 24(1), 576; https://doi.org/10.3390/ijms24010576 - 29 Dec 2022
Cited by 1 | Viewed by 3661
Abstract
The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in [...] Read more.
The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in vivo biotoxicity. Our main findings suggest that nanoparticles are generally able to reach the testicle in small quantities where they persist for several months, regardless of the route of exposure. However, there is not enough evidence that they can cross the blood–testis barrier. Of note, the majority of nanoparticles have low direct toxicity to the testis, but there are indications that some might act as endocrine disruptors. Overall, the impact on spermatogenesis in adults is generally weak and reversible, but exceptions exist and merit increased attention. Finally, we comment on several methodological or analytical biases which have led some studies to exaggerate the reprotoxicity of nanoparticles. In the future, rigorous clinical studies in tandem with mechanistic studies are needed to elucidate the real risk posed by nanoparticles on male fertility. Full article
(This article belongs to the Special Issue Advanced Research on Reproductive System Disease 2022)
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