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Biomedicines
Special Issues
Reproductive Medicine: Focus on Cell and Molecule
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Reproductive Medicine: Focus on Cell and Molecule

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 13191

Special Issue Editors

Prof. Dr. Ning Qu

E-Mail Website
Guest Editor
Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
Interests: reproductive immunology; spermatogenesis; oriental medicine; anti-cancer treatment
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Tomohiko Wakayama

E-Mail Website
Guest Editor
Department of Histology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
Interests: reproductive immunology; spermatogenesis

Special Issue Information

Dear Colleagues,

Reproductive medicine and biology are very important for maintaining and preserving successful pregnancy in both males and females, and interaction between the reproductive and immune systems enables the normal preservation of reproductive functions. Malfunctioning of the immune/reproductive interaction at any of these stages may result in predisposition to infertility. It is desired to make improved medical treatment and prognosis for infertility available to patients and physicians. The purpose of this Special Issue is to provide a global overview of reproduction with biomedical data generated from individuals, biological experiments, and environmental factors, to introduce new opportunities, and to pose challenges in clinical activities.

This Special Issue of Biomedicines invites colleagues to submit original research articles and up-to-date reviews in human and animal reproductive medicine, with special attention paid to cellular and molecular mechanism research, with the aim to provide new perspectives.

Dr. Ning Qu
Prof. Dr. Tomohiko Wakayama
Guest Editors

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • reproduction
  • infertility
  • spermatogenesis
  • oogenesis
  • animal reproduction
  • cellular and molecular structure
  • immunity

Published Papers (6 papers)

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Research

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11 pages, 1027 KiB  
Article
Should the Treatment of Patients with Repeated Embryo Implantation Failure Be Adapted as a Function of the Endometrial Cytokine Profile? A Single-Center Experience
by Bérangère Coutanceau, Esther Dos Santos, Nelly Swierkowski Blanchard, Anne Sanchez Louboutin, Florence Boitrelle, François Margueritte, François Vialard, Valérie Serazin and Khadija Fathallah
Biomedicines 2023, 11(3), 817; https://doi.org/10.3390/biomedicines11030817 - 7 Mar 2023
Viewed by 1494
Abstract
Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies [...] Read more.
Repeated embryo implantation failures (RIF) is a source of distress and frustration for patients and clinicians alike. Today’s approaches for treating RIF are largely empirical and have limited effectiveness. The main causes of RIF are poor endometrial receptivity and poor-quality embryos. Recent studies have suggested the involvement of immune dysregulation due to an imbalance between T-helper (Th) 1 and Th2 cytokines; this opens up perspectives for treating women with RIF and increasing the implantation rate. We conducted an interventional, longitudinal, prospective cohort study of the impact of correcting the cytokine imbalance on the clinical pregnancy rate in women with RIF. Seventy-seven women with RIF underwent an endometrial biopsy during the implantation window. The cytokine profile was evaluated by studying the activation and maturation of uterine natural killer (uNK) cells, the IL-15/Fn-14 mRNA ratio (a biomarker of uNK activation/maturation), and the IL-18/TWEAK mRNA ratio (a marker of angiogenesis and the Th1/Th2 balance). Personalized treatment was initiated for women with an abnormal endometrial cytokine profile (hyper-activation or hypo-activation). We documented the clinical pregnancy rate after subsequent embryo transfers. In total, 72.7% (56/77) of patients had an abnormal endometrial cytokine profile (hyper-activation in 68.8% (n = 53) and hypo-activation in 3.9% (n = 3). After treatment (or not) as a function of the endometrial profile, the overall clinical pregnancy rate was 30.2%. Our results indicated a potential positive effect of appropriate treatment on the ongoing pregnancy rate in women with RIF, despite the small number of cases analyzed. The results must now be validated in randomized studies with larger numbers of well-characterized patients. By applying a previously published decision tree, this treatment approach could be implemented in clinics worldwide. Full article
(This article belongs to the Special Issue Reproductive Medicine: Focus on Cell and Molecule)
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15 pages, 3653 KiB  
Article
Screening of Potential Plasticizer Alternatives for Their Toxic Effects on Male Germline Stem Cells
by Xiangfan Zhang and Makoto Nagano
Biomedicines 2022, 10(12), 3217; https://doi.org/10.3390/biomedicines10123217 - 12 Dec 2022
Cited by 1 | Viewed by 1104
Abstract
Plasticizers give flexibility to a wide range of consumer and medical plastic products. Among them, phthalate esters are recognized as endocrine disruptors that target male reproductive functions. With this notion, past studies designed and produced alternative plasticizers that could replace phthalates with limited [...] Read more.
Plasticizers give flexibility to a wide range of consumer and medical plastic products. Among them, phthalate esters are recognized as endocrine disruptors that target male reproductive functions. With this notion, past studies designed and produced alternative plasticizers that could replace phthalates with limited toxicity to the environment and to male reproductive functions. Here, we focused on one reproductive cell type that was not investigated in past studies—spermatogonial stem cells (SSCs)—and examined in vitro the effects on 22 compounds (seven plasticizers currently in use and 15 newly synthesized potential alternative plasticizers) for their effects on SSCs. Our in vitro compound screening analyses showed that a majority of the compounds examined had a limited level of toxicity to SSCs. Yet, some commercial plasticizers and their derivatives, such as DEHP (di-(2-ethylhexyl) phthalate) and MEHP (mono-(2-ethylhexyl) phthalate), were detrimental at 10−5 to 10−4 M. Among new compounds, some of maleate- and fumarate-derivatives showed toxic effects. In contrast, no detrimental effects were detected with two new compounds, BDDB (1,4 butanediol dibenzoate) and DOS (dioctyl succinate). Furthermore, SSCs that were exposed to BDDB and DOS in vitro successfully established spermatogenic colonies in testes of recipient mice after transplantation. These results demonstrate that SSC culture acts as an effective platform for toxicological tests on SSC function and provide novel information that two new compounds, BDDB and DOS, are alternative plasticizers that do not have significant negative impacts on SSC integrity. Full article
(This article belongs to the Special Issue Reproductive Medicine: Focus on Cell and Molecule)
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18 pages, 2893 KiB  
Article
Interleukin-33 Derived from Endometriotic Lesions Promotes Fibrogenesis through Inducing the Production of Profibrotic Cytokines by Regulatory T Cells
by Fengyi Xiao, Xishi Liu and Sun-Wei Guo
Biomedicines 2022, 10(11), 2893; https://doi.org/10.3390/biomedicines10112893 - 11 Nov 2022
Cited by 5 | Viewed by 1569
Abstract
In endometriosis, it has been widely believed that the local immunological milieu is Th2-skewed. Regulatory T cells (Tregs) promote fibrogenesis of endometriosis through the transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF) signaling pathways. We aimed to explore whether Tregs in [...] Read more.
In endometriosis, it has been widely believed that the local immunological milieu is Th2-skewed. Regulatory T cells (Tregs) promote fibrogenesis of endometriosis through the transforming growth factor β1 (TGF-β1) and platelet-derived growth factor (PDGF) signaling pathways. We aimed to explore whether Tregs in endometriotic lesions acquire increased production of effector cytokines under the influence of lesion-derived interleukin (IL)-33. We extracted lymphocytes from normal endometrium and ovarian endometrioma to evaluate the expression of IL-4, IL-13, interferon-γ (IFN-γ), TGF-β1, and the IL-33 receptor (ST2) by Tregs from these tissues. Colocalization of IL-33 and FOXP3 in normal endometrium and ovarian endometrioma was evaluated by immunofluorescence. Tregs and endometriotic stromal cells were co-cultured and treated with anti-IL-33 antibody, and the cytokines produced by Tregs were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Tregs in ovarian endometrioma produced significant amounts of IL-4, IL-13, TGF-β1, and ST2. Colocalization of IL-33 and FOXP3 was detected in ovarian endometrioma. IL-33 from endometriotic stromal cells caused the differentiation of lesional Tregs into type 2 T helper (Th2)-like cells, along with increased production of TGF-β1 by Tregs. Thus, Tregs and endometriotic lesions engage active crosstalk through IL-33 to promote fibrogenesis in endometriosis, and, as such, this finding opens up new avenues to identify novel therapeutic targets for endometriosis. Full article
(This article belongs to the Special Issue Reproductive Medicine: Focus on Cell and Molecule)
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9 pages, 1537 KiB  
Article
Risk Factors for Severe Erectile Dysfunction after Focal Therapy with High-Intensity Focused Ultrasound for Prostate Cancer
by Sunao Shoji, Satoshi Kuroda, Kohei Uemura, Kazuya Oda, Tatsuo Kano, Takahiro Ogawa, Tatsuya Umemoto, Mayura Nakano, Masayoshi Kawakami, Masahiro Nitta, Masanori Hasegawa and Akira Miyajima
Biomedicines 2022, 10(11), 2876; https://doi.org/10.3390/biomedicines10112876 - 10 Nov 2022
Cited by 3 | Viewed by 1513
Abstract
The present study aimed to analyze the effect of predisposing clinical factors for severe erectile dysfunction (ED) in patients treated with focal therapy using high-intensity focused ultrasound (HIFU) for localized prostate cancer (PC). Patients without severe ED (International Index of Erectile Function-5 [IIEF-5] [...] Read more.
The present study aimed to analyze the effect of predisposing clinical factors for severe erectile dysfunction (ED) in patients treated with focal therapy using high-intensity focused ultrasound (HIFU) for localized prostate cancer (PC). Patients without severe ED (International Index of Erectile Function-5 [IIEF-5] score ≥ 8) before focal HIFU therapy were included. A total of 92 of the 240 patients met the inclusion criteria and were included. The rate of severe ED (IIEF-5 ≤ 7) was 36% 12 months after treatment. Multivariable logistic regression analysis showed that the pre-procedural lower IIEF-5 score (odds ratio [OR] 0.812, p = 0.005), the pre-procedural lower score of the sexual domain of the Expanded Prostate Cancer Index Composite (OR 0.960, p = 0.038), and the treatment of the edge of the peripheral zone (PZ) in proximity to the neurovascular bundle (NVB) [treated vs. untreated, OR 8.048, p = 0.028] were significant risk factors for severe ED at 12 months after treatment. In conclusion, pre-procedural lower erectile function and treatment of the part in proximity to the NVB were significant risk factors for severe ED after focal therapy. Full article
(This article belongs to the Special Issue Reproductive Medicine: Focus on Cell and Molecule)
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19 pages, 7436 KiB  
Article
Obesity-Related Genes Expression in Testes and Sperm Parameters Respond to GLP-1 and Caloric Restriction
by Ana S. Correia, Sara C. Pereira, Tiago Morais, Ana D. Martins, Mariana P. Monteiro, Marco G. Alves and Pedro F. Oliveira
Biomedicines 2022, 10(10), 2609; https://doi.org/10.3390/biomedicines10102609 - 17 Oct 2022
Cited by 1 | Viewed by 1631
Abstract
Aim: Calorie restriction (CR) diets and glucagon-Like Peptide-1 (GLP-1) analogs are known to alter energy homeostasis with the potential to affect the expression of obesity-related genes (ORGs). We hypothesized that CR and GLP-1 administration can alter ORGs expression in spermatozoa and testes, [...] Read more.
Aim: Calorie restriction (CR) diets and glucagon-Like Peptide-1 (GLP-1) analogs are known to alter energy homeostasis with the potential to affect the expression of obesity-related genes (ORGs). We hypothesized that CR and GLP-1 administration can alter ORGs expression in spermatozoa and testes, as well as the sperm parameters implicated in male fertility. Materials and Methods: Six-week-old adult male Wistar rats (n = 16) were divided into three groups, submitted either to CR (n = 6, fed with 30% less chow diet than the control rats), GLP-1 administration (n = 5, 3.5 pmol/min/kg intraperitoneal) for 28 days, or used as controls (n = 5, fed ad libitum). Selected ORGs expression, namely the fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), glucosamine-6-phosphate deaminase 2 (GNPDA2), and transmembrane protein 18 (TMEM18) were evaluated in testes and spermatozoa by a quantitative polymerase chain reaction (qPCR). Results: CR resulted in lower body weight gain and insulin resistance, but a higher percentage of sperm head defects. GLP-1 administration, despite showing no influence on body weight or glucose homeostasis, resulted in a lower percentage of sperm head defects. CR and GLP-1 administration were associated with a higher expression of all ORGs in the testes. Under CR conditions, the genes FTO and TMEM18 expression in the testes and the MC4R and TMEM18 transcripts abundance in sperm were positively correlated with the spermatozoa oxidative status. The abundance of FTO and TMEM18 in the spermatozoa of rats under CR were positively correlated with sperm concentration, while the testes’ TMEM18 expression was also positively correlated with sperm vitality and negatively correlated with insulin resistance. Testes GNPDA2 expression was negatively correlated with sperm head defects. Conclusions: CR and GLP-1 administration results in higher ORGs expression in testes, and these were correlated with several alterations in sperm fertility parameters. Full article
(This article belongs to the Special Issue Reproductive Medicine: Focus on Cell and Molecule)
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Review

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38 pages, 2809 KiB  
Review
An Interplay between Epigenetics and Translation in Oocyte Maturation and Embryo Development: Assisted Reproduction Perspective
by Michal Dvoran, Lucie Nemcova and Jaroslav Kalous
Biomedicines 2022, 10(7), 1689; https://doi.org/10.3390/biomedicines10071689 - 13 Jul 2022
Cited by 7 | Viewed by 5254
Abstract
Germ cell quality is a key prerequisite for successful fertilization and early embryo development. The quality is determined by the fine regulation of transcriptomic and proteomic profiles, which are prone to alteration by assisted reproduction technology (ART)-introduced in vitro methods. Gaining evidence shows [...] Read more.
Germ cell quality is a key prerequisite for successful fertilization and early embryo development. The quality is determined by the fine regulation of transcriptomic and proteomic profiles, which are prone to alteration by assisted reproduction technology (ART)-introduced in vitro methods. Gaining evidence shows the ART can influence preset epigenetic modifications within cultured oocytes or early embryos and affect their developmental competency. The aim of this review is to describe ART-determined epigenetic changes related to the oogenesis, early embryogenesis, and further in utero development. We confront the latest epigenetic, related epitranscriptomic, and translational regulation findings with the processes of meiotic maturation, fertilization, and early embryogenesis that impact the developmental competency and embryo quality. Post-ART embryo transfer, in utero implantation, and development (placentation, fetal development) are influenced by environmental and lifestyle factors. The review is emphasizing their epigenetic and ART contribution to fetal development. An epigenetic parallel among mouse, porcine, and bovine animal models and human ART is drawn to illustrate possible future mechanisms of infertility management as well as increase the awareness of the underlying mechanisms governing oocyte and embryo developmental complexity under ART conditions. Full article
(This article belongs to the Special Issue Reproductive Medicine: Focus on Cell and Molecule)
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