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Molecular Research in Reproductive Biology

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A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 19096

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Special Issue Editors

Dr. Hoon Jang

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Guest Editor

Department of Life Sciences, Jeonbuk National University, Jeonju 54896, Republic of Korea
Interests: ovarian follicle development; spermatogenesis; uterus implantation; optogenetics
Special Issues, Collections and Topics in MDPI journals

Dr. In-Sul Hwang

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Guest Editor

Columbia Center for Translational Immunology, Columbia University Irving Medical Center, Columbia University, New York, NY 10032, USA
Interests: reproductive biology; assisted reproductive technology; xenotransplantation; pig; SCNT; cryopreservation

Special Issue Information

Dear Colleagues,

The preservation of fertility is critical to maintaining successful pregnancies in both men and women, and the study of fertility is essential to enhance reproduction. Recently, infertility is increasing due to genetic or environmental factors that cause the abnormal development of reproductive organs or the death of germ cells. Therefore, it is crucial for drug development to identify the exact elements that cause the abnormal development of reproductive organs and toxicity, and to identify the associated molecular mechanisms. Additionally, researchers are currently in the process of developing biomedicine that actively uses microbiomes that coexist with humans on a molecular level; thus, research should focus on the relationship between intrauterine microbes and embryo implantation ability. Therefore, the study of molecular mechanisms in reproductive biology could provide better knowledge to overcome infertility associated with the protection and development of the reproductive system. For this Special Issue, we invite potential researchers working on revealing the causes of infertility and solving this problem by investigating the molecular biology of the development, differentiation, and toxicity of reproductive organs.

Prof. Dr. Hoon Jang
Dr. In-Sul Hwang
Guest Editors

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Keywords

reproductive biology
assisted reproductive technology
ovarian follicle development
spermatogenesis

Published Papers (10 papers)

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Research

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21 pages, 1479 KiB

Open AccessArticle

Molecular Role of Asn680Ser and Asp37Glu Missense Variants in Saudi Women with Female Infertility and Polycystic Ovarian Syndrome

by Amal F. Alshammary, Sarah F. Alsobaie, Arwa A. Alageel, Fahad M. Aldakheel, Sabah Ansar, Reem Alrashoudi, Raed Farzan, Norah A. Alturki, Maysoon Abdulhadi Alhaizan, Johara Al-Mutawa and Imran Ali Khan

Curr. Issues Mol. Biol. 2023, 45(7), 5494-5514; https://doi.org/10.3390/cimb45070348 - 29 Jun 2023

Cited by 4 | Viewed by 1388

Abstract

Female infertility (FI) is a global health issue. Polycystic ovary syndrome (PCOS) is a common cause of FI. The renalase gene (RNLS) is associated with FI and other human diseases. Based on the documented missense variants, rs6166 and rs2296545 single-nucleotide polymorphisms (SNPs) were not identified in Saudi women with FI and PCOS. This study aimed to investigate the molecular role of the two SNPs in Saudi women with FI and PCOS. In this cross-sectional study, 96 healthy controls, 96 women with FI, and 96 women with PCOS were recruited. DNA was isolated, and polymerase chain reactions and Sanger sequencing analysis were performed using rs6166 and rs2296545 SNPs. The data obtained from the three groups were used to perform statistical analyses based on genotype, allele frequencies, regression models, and ANOVA analysis. Both rs6166 and rs2296545 had no role in FI or PCOS in Saudi women. A predicted reason for non-association in Saudi women could be the role of elderly women in the controls compared with women with FI and PCOS. Moreover, age, weight, and body mass index were higher in the control group than the FI and PCOS groups. In conclusion, rs6166 and rs2296545 SNPs were not associated with FI or PCOS in Saudi women. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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13 pages, 47245 KiB

Open AccessArticle

Protective Effect of Curculigo orchioides Gaertn. Extract on Heat Stress-Induced Spermatogenesis Complications in Murine Model

by Thanh-Nhan Bui-Le, Quang Hoang-Tan, Huong Hoang-Viet, Bich-Phuong Truong-Thi and Tung Nguyen-Thanh

Curr. Issues Mol. Biol. 2023, 45(4), 3255-3267; https://doi.org/10.3390/cimb45040212 - 07 Apr 2023

Cited by 3 | Viewed by 1787

Abstract

Curculigo orchioides Gaertn. is a precious herb used in traditional medicine systems in Asian countries for various health benefits. This study investigated the potential protective effects of C. orchioides extract on reproductive health under heat stress conditions in male mice. Forty-eight mice were divided into eight groups, control condition (C group), C. orchioides extract at the dosages of 100, 200, and 400 mg/kg/day (C100, C200, C400 group), 40 °C heat exposure (H group), and combined 40 °C heat exposure and C. orchioides extract at the dosages of 100, 200, and 400 mg/kg/day (HC100, HC200, HC400 group). The result shows that the mice that received only C. orchioides extract without heat stress do not have a significant change in histological structure and testosterone level. The histological analysis of testicular tissue showed that heat stress conditions reduced reproductive function and inhibited the spermatogenesis of male mice. The C. orchioides rhizome extract treatment attenuated the heat stress-induced spermatogenesis complications in the murine model. Mice in the heat-stress group treated with C. orchioides extract had increased spermatogenic cells and spermatozoa compared with mice exposed to heat without C. orchioides treatment. Moreover, the aqueous extract of C. orchioides rhizome enhanced the serum total testosterone levels in heat-exposed mice. In conclusion, the study findings validate that C. orchioides is effective against heat stress-induced spermatogenesis complications in the murine model. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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12 pages, 2250 KiB

Open AccessArticle

Effect of C-Type Natriuretic Peptide (CNP) on Spermatozoa Maturation in Adult Rat Epididymis

by Hu Zhao, Yuejin Yu, Chunlei Mei, Tianyu Zhang, Yafei Kang, Na Li and Donghui Huang

Curr. Issues Mol. Biol. 2023, 45(2), 1681-1692; https://doi.org/10.3390/cimb45020108 - 16 Feb 2023

Cited by 1 | Viewed by 1680

Abstract

C-type natriuretic peptide (CNP) is highly expressed in male reproductive tissues, such as the epididymis. The aim of this study is to explore the role of CNP in the maturation of rat epididymal spermatozoa. First, the expression levels of CNP and its specific natriuretic peptide receptor-B (NPR-B) were detected in various tissues of rats and epididymis at different stages after birth. Then a castrated rat model was established to analyze the relationship between testosterone and CNP/NPR-B expression in the epididymis. Finally, CNP and different inhibitors (NPR-B inhibitors, cGMP inhibitors) were used to incubate epididymal sperm in vitro to examine sperm mobility and expression of sperm maturation-related factors. The results showed CNP/NPR-B mRNAs were expressed in all tissues of rats, but were extremely highly expressed in male genital ducts (seminal vesicle, prostate and epididymis). The expression of CNP/NPR-B in epididymis was the highest at birth and the fifth week after birth. In the epididymis, CNP/NPR-B were highly expressed in the caput and located in the epididymal epithelial cells. After castration, the expression of CNP/NPR-B decreased sharply and was restored quickly after testosterone supplementation. In vitro, CNP could significantly promote the acquisition of epididymal sperm motility through the NPR-B/cGMP pathway and induce the expression of sperm maturation-related factors (such as Bin1b, Catsper 1, Dnah17, Fertilin). This study shows that CNP plays a role in epididymal sperm maturation. The mechanism of CNP is to promote the acquisition of epididymal sperm fluidity through the NPR-B/cGMP signaling pathway and also to regulate sperm maturation-related genes. Moreover, the expression of CNP/NPR-B was regulated by testosterone. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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16 pages, 4637 KiB

Open AccessArticle

Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis

by Zhi-Hui Yi, Shu-Qing Li, Jun-Ya Ke, Yun Wang, Ming-Zhi Zhao, Jing Li, Ming-Qing Li and Zhi-Ling Zhu

Curr. Issues Mol. Biol. 2022, 44(12), 6189-6204; https://doi.org/10.3390/cimb44120422 - 07 Dec 2022

Cited by 5 | Viewed by 2145

Abstract

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells’ phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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12 pages, 8176 KiB

Open AccessArticle

Altered Expression of Interleukin-18 System mRNA at the Level of Endometrial Myometrial Interface in Women with Adenomyosis

by Liang-Hsuan Chen, She-Hung Chan, Chin-Jung Li, Hsien-Ming Wu and Hong-Yuan Huang

Curr. Issues Mol. Biol. 2022, 44(11), 5550-5561; https://doi.org/10.3390/cimb44110376 - 09 Nov 2022

Cited by 2 | Viewed by 1620

Abstract

Adenomyosis is a uterine pathology characterized by a deep invasion of endometrial glands and stroma, disrupting the endometrial–myometrial interface (EMI). Interleukin-18 (IL-18) system is a dominant cytokine involved in the menstrual cycle of human endometrium. IL-18 may play a defensive role against maternal immune response in the uterine cavity. The present study was designed to determine IL-18-mediated immune response at the level of EMI. We uncovered that mRNA of IL-18 system, including IL-18, IL-18 receptor (IL-18R), and its antagonist, IL-18 binding protein (IL-18BP), expressed in eutopic, ectopic endometrium, and corresponding myometrium in patients with adenomyosis. IL-18 system was demonstrated in paired tissue samples by immunochemistry and immunofluorescence study. According to RT-PCR with C_T value quantification and 2^−∆∆Ct method, a significant down-regulation of IL-18BP in corresponding myometrium in comparison to eutopic endometrium (p < 0.05) indicates that the IL-18 system acts as a local immune modulator at the level of EMI and regulating cytokine networks in the pathogenesis of adenomyosis. Furthermore, an increased IL-18 antagonist to agonist ratio was noted in ectopic endometrium compared with corresponding myometrium. We suggest that altered IL-18 system expression contributes to immunological dysfunction and junctional zone disturbance in women with adenomyosis. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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12 pages, 1593 KiB

Open AccessArticle

Influence of Technological Stages of Preparation of Rooster Semen for Short-Term and Long-Term Storage on Its Quality Characteristics

by Yulia Silyukova, Elena Fedorova and Olga Stanishevskaya

Curr. Issues Mol. Biol. 2022, 44(11), 5531-5542; https://doi.org/10.3390/cimb44110374 - 07 Nov 2022

Cited by 3 | Viewed by 1713

Abstract

There is a problem of declining quality of rooster semen in the “native semen-equilibrium-short-term and long-term storage (cryopreservation)” cycle. The aim of this study was to determine the effects of various methods of preparing rooster semen on its qualitative characteristics, taking into account the method of removing possible contaminants (centrifugation or filtration), and to evaluate the change in the composition of the cytosol of the spermatozoon of the native semen, during equilibration of the diluted semen and during short-term storage. In this study, semen from roosters (n = 22) of the Russian White breed was used. Experiment 1: semen was divided into 3 aliquots: I—was diluted with synthetic cryoprotective medium (1:1 with LCM control, II—was filtered (membrane pore Ø 0.2 μm), and III—was centrifugated (at 3000 rpm for 10 min). Native and frozen/thawed semen was evaluated. Experiment 2: the composition of carbohydrates and polyols of the spermatozoa of native semen was evaluated during equilibration and after storage (3 h). The results of Experiment 1 showed an advantage in the quality of filtered semen compared to centrifuged in terms of progressive motility (41.0% vs. 27.0%) and chromatin integrity (56.6% vs. 33.6%). Results from frozen/thawed samples of filtered semen compared to centrifuged in terms of progressive motility were 25.5% vs. 5.5%, respectively, and in terms of chromatin integrity—83.5% vs. 64.4%, respectively. The results of Experiment 2 showed the main component in the composition of the native spermatozoa cytosol in assessing the content of carbohydrates and polyols was inositol—75.6%. The content of inositol decreased during storage by 6.5 times (from 0.030 mg/mL to 0.007 mg/mL), proposing the role of inositol as the main antioxidant in the cytosol of spermatozoa, which makes it biologically justified to introduce inositol into the composition of synthetic diluents, including cryoprotective ones. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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Review

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21 pages, 779 KiB

Open AccessReview

Disrupted Balance of the Oxidant–Antioxidant System in the Pathophysiology of Female Reproduction: Oxidative Stress and Adverse Pregnancy Outcomes

by József Gábor Joó, Endre Sulyok, József Bódis and László Kornya

Curr. Issues Mol. Biol. 2023, 45(10), 8091-8111; https://doi.org/10.3390/cimb45100511 - 04 Oct 2023

Cited by 1 | Viewed by 1685

Abstract

The significance of oxidative stress in the pathophysiology of male reproductive processes has been closely studied in the last two decades. Recently, it has become clear that oxidative stress can lead to numerous pathological conditions during female reproductive processes as well, contributing to the development of endometriosis, polycystic ovary syndrome and various forms of infertility. During pregnancy, physiological generation of reactive oxygen species (ROS) occurs in association with several developmental processes including oocyte maturation and implantation. An overproduction of ROS can lead to disturbances in fetal development and increases the risk for missed abortion, intrauterine growth restriction, pre-eclampsia, premature delivery and gestational diabetes. Our review focuses on the etiological role of the disrupted oxidant–antioxidant system during human gestation as it relates to adverse pregnancy outcomes. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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16 pages, 1156 KiB

Open AccessReview

The Chemosensing Role of CatSper in Mammalian Sperm: An Updated Review

by Sulun Ke and Tao Luo

Curr. Issues Mol. Biol. 2023, 45(9), 6995-7010; https://doi.org/10.3390/cimb45090442 - 23 Aug 2023

Viewed by 1427

Abstract

After sperm enter the female reproductive tract, the physicochemical and biochemical microenvironment undergoes significant changes. In particular, the large changes in various ions encountered by sperm may alter the physiology of sperm, ultimately compromising capacitation and fertilization. Thus, the rapid response to environmental variations is vital for sperm functions. For example, Calcium, the most crucial ion for sperm functions, enters into sperm via Ca²⁺ permeable ion channels. The cation channel of sperm (CatSper) is a sperm-specific, pH-sensitive, and Ca²⁺-permeable ion channel. It is responsible for the predominant Ca²⁺ entry in mammalian sperm and is involved in nearly every event of sperm to acquire fertilizing capability. In addition, CatSper also serves as a pivotal polymodal chemosensor in mammalian sperm by responding to multiple chemical cues. Physiological chemicals (such as progesterone, prostaglandins, β-defensins, and odorants) provoke Ca²⁺ entry into sperm by activating CatSper and thus triggering sperm functions. Additionally, synthetic and natural chemicals (such as medicines, endocrine disrupting chemicals, drugs of abuse, and antioxidants) affect sperm functions by regulating CatSper-dependent Ca²⁺ signaling. Therefore, understanding the interactions between CatSper and extracellular ligands sheds light on the mechanisms underlying male infertility and offers innovative diagnostic and treatment approaches. This underscores the importance of CatSper as a crucial regulatory target in male reproduction, linking sperm function with the extracellular environment. In conclusion, this review comprehensively summarizes the relevant studies describing the environmental factors that affect CatSper in humans and rodents. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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15 pages, 1286 KiB

Open AccessReview

Oxidative Stress in Assisted Reproductive Techniques, with a Focus on an Underestimated Risk Factor

by Péter Mauchart, Réka Anna Vass, Bernadett Nagy, Endre Sulyok, József Bódis and Kálmán Kovács

Curr. Issues Mol. Biol. 2023, 45(2), 1272-1286; https://doi.org/10.3390/cimb45020083 - 03 Feb 2023

Cited by 8 | Viewed by 1915

Abstract

Based on current findings, the presence of oxidative stress has a significant impact on the quality of gametes and embryos when performing assisted reproductive techniques (ART). Unfortunately, in vitro manipulation of these cells exposes them to a higher level of reactive oxygen species (ROS). The primary goal of this review is to provide a comprehensive overview of the development of oxidative stress in female and male reproductive systems, as well as in the case of the pre-implantation embryo and its environment. This review also focuses on the origins of ROS and the mechanisms of oxidative stress-induced damage during ART procedures. A well-known but underestimated hazard, light exposure-related photo-oxidation, is particularly concerning. The effect of oxidative stress on ART outcomes, as well as the various strategies for preventing it, are also discussed. We emphasize the role and significance of antioxidants and light protection including forms, functions, and mechanisms in the development of gametes and embryos in vivo and in vitro. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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17 pages, 999 KiB

Open AccessReview

Immunotherapeutic Approaches in Ovarian Cancer

by Hyunho Yoon, Ayoung Kim and Hoon Jang

Curr. Issues Mol. Biol. 2023, 45(2), 1233-1249; https://doi.org/10.3390/cimb45020081 - 02 Feb 2023

Cited by 5 | Viewed by 2395

Abstract

Ovarian cancer (OC) is gynecological cancer, and diagnosis and treatment are continuously advancing. Next-generation sequencing (NGS)-based diagnoses have emerged as novel methods for identifying molecules and pathways in cancer research. The NGS-based applications have expanded in OC research for early detection and identification of aberrant genes and dysregulation pathways, demonstrating comprehensive views of the entire transcriptome, such as fusion genes, genetic mutations, and gene expression profiling. Coinciding with advances in NGS-based diagnosis, treatment strategies for OC, such as molecular targeted therapy and immunotherapy, have also advanced. Immunotherapy is effective against many other cancers, and its efficacy against OC has also been demonstrated at the clinical phase. In this review, we describe several NGS-based applications for therapeutic targets of OC, and introduce current immunotherapeutic strategies, including vaccines, checkpoint inhibitors, and chimeric antigen receptor (CAR)-T cell transplantation, for effective diagnosis and treatment of OC. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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