Article
Reproductive Biology
Hayden Holmlund, Yasuhiro Yamauchi, Gerald Durango, Wataru Fujii, Monika A. Ward
Summary: We generated Prssly and Teyorf1 knockout mice using CRISPR/Cas9 technology, and found that these genes are dispensable for male fertility as the knockout mice displayed normal spermatogenic features.
BIOLOGY OF REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Alenka Hodzic, Ales Maver, Branko Zorn, Daniel Petrovic, Tanja Kunej, Borut Peterlin
Summary: This study aimed to identify genes involved in the pathogenesis of idiopathic male infertility based on transcriptomic and genomic data. By analyzing gene expression in testis biopsy samples and conducting a systematic review, four genes were found to be associated with male infertility, while three other genes were identified as promising candidates.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Xiaoli Wang, Lisha Yin, Yujiao Wen, Shuiqiao Yuan
Summary: Mitochondria adjust their morphology to suit different cell types and environments, playing important roles in spermatogenesis. Deficiencies in mitochondria can cause male infertility and regulate piRNA biogenesis. This review describes the characteristics of mitochondria, focusing on key mitochondrial factors and the underlying molecular mechanisms in spermatogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Verena Hoeffken, Sara Di Persio, Sandra Laurentino, Margot J. Wyrwoll, Nicole Terwort, Anke Hermann, Albrecht Roepke, Manon S. Oud, Joachim Wistuba, Sabine Kliesch, Hermann J. Pavenstaedt, Frank Tuettelmann, Nina Neuhaus, Joachim Kremerskothen
Summary: The WWC protein family regulates cell proliferation and organ growth control via the Hippo signaling pathway. WWC2 has a relatively high expression in the testis and is associated with spermatogenesis and male fertility. Rare variants of the WWC2 gene may be linked to male infertility.
Review
Obstetrics & Gynecology
Indrashis Bhattacharya, Souvik Sen Sharma, Subeer S. Majumdar
Summary: Spermatogenesis is a complex process involving interactions between germ cells and testicular cells. Male infertility can be caused by congenital abnormalities, genetic mutations, endocrine/metabolic dysfunction, environmental toxicant exposure, and lifestyle-related disorders. Despite extensive research, a significant number of infertility cases remain idiopathic, highlighting the need for a better understanding of the regulation of spermatogenesis. Dysfunction of testicular Sertoli cells has emerged as a potential underlying cause of male infertility.
REPRODUCTIVE SCIENCES
(2023)
Article
Endocrinology & Metabolism
Weihao Sun, Xinhui Zhang, Lei Wang, Guanyu Ren, Shuguang Piao, Chenghua Yang, Zhiyong Liu
Summary: The study investigated the histological changes and molecular mechanisms in cryptorchidism patients aged 20 to 40 years. Results showed a significant atrophy and decline in spermatogenic cells in the testes of patients with longer disease duration, with downregulation of genes related to sperm development and differentiation, providing insights into the decline in fertility in adult cryptorchidism.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Guohui Zhang, Chuan Jiang, Yushang Yang, Yan Wang, Haimeng Zhou, Siyu Dai, Mohan Liu, Yanting Yang, Li Yang, Qiongyan Shen, Tao Zhang, Xiaodong Zhang, Yihong Yang, Ying Shen
Summary: In this study, we reported male infertility patients with a hemizygous nonsense mutation in the cancer-testis antigen 55 (CT55) gene, which resulted in extreme disruption in sperm production, morphology, and locomotion. Our functional experiments revealed that CT55 acts as a novel autophagic manipulator involved in spermatogenesis.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Thomas Greither, Hermann M. Behre, Holger Herlyn
Summary: Deciphering the functional relationships between genes associated with phenotypic variations can be challenging. In this study, a genome-wide association study (GWAS) linked twelve non-synonymous single-nucleotide polymorphisms (SNPs) to fertility variation in men. These SNPs were located in nine genes that have been previously implicated in male fertility. The study also identified potential biomarkers for the diagnosis of male fertility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yusuke Takahashi, Hidetaka Kioka, Shinichiro Fukuhara, Sohei Kuribayashi, Shigeyoshi Saito, Yoshihiro Asano, Seiji Takashima, Yoshichika Yoshioka, Yasushi Sakata
Summary: This study investigated the utility of CrCEST imaging in evaluating spermatogenesis and its spatial distribution, showing a strong correlation between testicular CrCEST effects and spermatogenesis.
JOURNAL OF MAGNETIC RESONANCE IMAGING
(2021)
Article
Developmental Biology
Siyu Liu, Jintao Zhang, Zine Eddine Kherraf, Shuya Sun, Xin Zhang, Caroline Cazin, Charles Coutton, Raoudha Zouari, Shuqin Zhao, Fan Hu, Selima Fourati Ben Mustapha, Christophe Arnoult, Pierre F. Ray, Mingxi Liu
Summary: This study reveals the pathogenic mechanism related to ciliary and flagellar motility defects caused by CFAP61 gene mutations. The research on CFAP61 splice variant c.143+5G>A demonstrates the impact of exon skipping/intron retention on flagellar morphology. Additionally, the study uncovers the important role of CFAP61 in male infertility.
Article
Biochemistry & Molecular Biology
Manuel Gentiluomo, Alice Luddi, Annapaola Cingolani, Marco Fornili, Laura Governini, Ersilia Lucenteforte, Laura Baglietto, Paola Piomboni, Daniele Campa
Summary: The study found no significant association between sperm telomere length (STL) and leukocyte telomere length (LTL) with sperm quality parameters, but identified five single nucleotide polymorphisms (SNPs) that were statistically significantly associated with sperm variables. The results suggest moderate involvement of telomere length in male fertility, while indicating the potential pleiotropic effects of certain SNPs on sperm parameters independent of telomere homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Shengnan Gong, Shiyao Zhu, Peng Zhou, C. Yan Cheng, Wenqing Li, Weiwei Yao, Fei Sun
Summary: There is a significant demand for safe and effective non-hormonal male contraceptives, but research on male contraceptive drugs has lagged behind that of female birth control pills. However, a new potential male contraceptive candidate, BHD, has been developed through the design and synthesis of a new series of molecules derived from lonidamine. BHD demonstrated a 100% contraceptive effect on male mice and rats, reducing fertility to 90% and 50% respectively after 6 weeks of treatment. BHD also induced rapid apoptosis of spermatogenic cells and effectively disrupted the blood-testis barrier.
Review
Chemistry, Medicinal
Neil R. Norcross, Irene Georgiou, Zoe C. Johnston, Franz S. Gruber, Jason R. Swedlow, Kevin D. Read, Christopher LR. Barratt, Ian H. Gilbert
Summary: This article discusses the need for male contraceptives and explores the characteristics and potential development pathways of male contraceptives. It also examines various approaches to discovering male contraceptives and highlights potential targets discussed in the literature.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Jose Luiz P. R. Jivago, Juliana Lis Mendes Brito, Gustavo Capistrano, Marcus Vinicius-Araujo, Ediron Lima Verde, Andris Figueiroa Bakuzis, Paulo E. N. Souza, Ricardo Bentes Azevedo, Carolina Madeira Lucci
Summary: The study found that testicular MNH is highly effective as a non-surgical sterilization method for animals, causing progressive seminiferous tubule degeneration followed by substitution of the parenchyma with stromal tissue and gonadal atrophy, suggesting an irreversible process with few side effects to general animal health.
Article
Biochemistry & Molecular Biology
Chunlan Long, Yu Zhou, Lianju Shen, Yihang Yu, Dong Hu, Xing Liu, Tao Lin, Dawei He, Tao Xu, Deying Zhang, Jing Zhu, Guanghui Wei
Summary: This study found that RA supplementation can up-regulate the expression of c-Kit, Stra8, and Sycp3 by activating RARa in neonatal cryptorchid infertile rats. RA can also inhibit the protein expression of the PI3K-Akt-mTOR signaling pathway and promote autophagy in cryptorchid testes.
Article
Andrology
Yuki Oyama, Haruhiko Miyata, Keisuke Shimada, Yoshitaka Fujihara, Keizo Tokuhiro, Thomas X. Garcia, Martin M. Matzuk, Masahito Ikawa
Summary: In this study, KO mice were generated for 12 testis-enriched genes using the CRISPR/Cas9 system. The mating tests of these KO mice revealed that these genes are not essential for male fertility, at least when individually ablated. Our results could prevent duplicative efforts in generating KO mice with no apparent phenotype.
ASIAN JOURNAL OF ANDROLOGY
(2022)
Review
Endocrinology & Metabolism
Daiji Kiyozumi, Masahito Ikawa
Summary: Proteolysis is not only involved in degrading unnecessary proteins, but also plays pivotal roles in regulating various biological processes by activating and inactivating proteins. Abnormalities in proteolysis can cause diseases, and recent studies have shown that proteolysis is also important in reproductive processes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biology
Taichi Noda, Andreas Blaha, Yoshitaka Fujihara, Krista R. Gert, Chihiro Emori, Victoria E. Deneke, Seiya Oura, Yonggang Lu, Sara Berent, Mayo Kodani, Karin Panser, Luis Enrique Cabrera-Quio, Andrea Pauli, Masahito Ikawa
Summary: DCST1 and DCST2 are essential factors for successful fertilization in vertebrates, playing a crucial role in male fertility.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biology
Kaori Nozawa, Yoshitaka Fujihara, Darius J. Devlin, Ricardo E. Deras, Katarzyna Kent, Irina V. Larina, Kohei Umezu, Zhifeng Yu, Courtney M. Sutton, Qiuji Ye, Laura K. Dean, Chihiro Emori, Masahito Ikawa, Thomas X. Garcia, Martin M. Matzuk
Summary: Our study identified four evolutionarily conserved testis-specific E3 ubiquitin-protein ligases (Rnf133, Rnf148, Rnf151, and Zswim2) and revealed that RNF133 is critical for sperm function during spermiogenesis. We hypothesize that RNF133, with its transmembrane domain, interacts with the ER-containing E2 protein UBE2J1 to function in ER quality control during spermatogenesis.
Article
Andrology
Yoshitaka Fujihara, Kiyonori Kobayashi, Ferheen Abbasi, Tsutomu Endo, Zhifeng Yu, Masahito Ikawa, Martin M. Matzuk
Summary: In this study, Pdcl2 knockout mice were generated to investigate the essential roles of PDCL2 in mammalian reproduction. The findings showed that PDCL2 is crucial for sperm acrosome development and male fertility, suggesting it as a potential contraceptive target in men.
Article
Andrology
Kaori Nozawa, Thomas X. Garcia, Katarzyna Kent, Mei Leng, Antrix Jain, Anna Malovannaya, Fei Yuan, Zhifeng Yu, Masahito Ikawa, Martin M. Matzuk
Summary: The importance of phosphorylation in sperm during spermatogenesis has been studied in this research, with a focus on testis-specific serine kinase 3 (Tssk3). It was found that TSSK3 plays a crucial role in male fertility and phosphorylation of infertility-related proteins. The absence of TSSK3 leads to disorganization of testicular seminiferous epithelium, reduced sperm counts, and abnormal sperm morphology. These findings have implications for understanding male infertility and developing nonhormonal contraception methods.
Article
Andrology
Qiuji Ye, Hassane Belabed, Yong Wang, Zhifeng Yu, Murugesan Palaniappan, Jian-Yuan Li, Stacey A. Kalovidouris, Kevin R. MacKenzie, Mingxing Teng, Damian W. Young, Yoshitaka Fujihara, Martin M. Matzuk
Summary: By developing a biophysical assay and using DNA-encoded chemical library (DECL) screening and off-DNA hit validation strategy, this study discovered a PDCL2 ligand for male contraception. The binding affinity between the PDCL2 ligand and PDCL2 was confirmed and determined by an affinity selection mass spectrometry assay combined with liquid chromatography tandem mass spectrometry (ASMS/LC-MS/MS).
Article
Biochemistry & Molecular Biology
Minako Yokoyama, Toshitsugu Fujita, Yuka Kadonosawa, Yota Tatara, Daisuke Motooka, Masahito Ikawa, Hodaka Fujii, Yoshihito Yokoayama
Summary: CBR1 is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase with broad substrate specificity. This study generated transgenic mice overexpressing CBR1 and characterized the expression of CBR1 in various organs, as well as identified changes in protein expression patterns. The transgenic mice may be useful for further understanding the molecular mechanisms regulated by CBR1 and its effects on carcinogenesis and cardiotoxicity of certain cancer drugs.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Andrology
Yonggang Lu, Ippei Nagamori, Hisato Kobayashi, Kanako Kojima-Kita, Kenjiro Shirane, Hsin-Yi Chang, Toru Nishimura, Takayuki Koyano, Zhifeng Yu, Julio M. Castaneda, Makoto Matsuyama, Satomi Kuramochi-Miyagawa, Martin M. Matzuk, Masahito Ikawa
Summary: In this study, Adad2 mutant mouse models were generated using CRISPR/Cas9 technology. It was found that male-specific sterility occurred in Adad2 mutant mice due to abnormal spermiogenesis. Furthermore, ADAD2 was shown to interact with multiple RNA-binding proteins involved in piRNA biogenesis and form novel granules with RNF17 in spermatocytes. These findings indicate that ADAD2 plays an important role in piRNA biogenesis.
Article
Andrology
Rie Iida-Norita, Haruhiko Miyata, Yuki Kaneda, Chihiro Emori, Taichi Noda, Tatsuya Nakagawa, Martin M. M. Matzuk, Masahito Ikawa
Summary: This study established a human LDHC knock-in mouse model and found that hLDHC KI mice could be used to assess the effectiveness of LDHC-targeting drugs, which is significant for preclinical contraceptive research.
Article
Andrology
Yuki Kaneda, Haruhiko Miyata, Keisuke Shimada, Seiya Oura, Masahito Ikawa
Summary: The knockout of TSNAXIP1 and 1700010I14Rik genes in mice resulted in reduced male fertility and impaired sperm motility. Unlike the TSNAX gene knockout, TSNAXIP1 and 1700010I14RIK may play a role in regulating sperm flagellar beating patterns.
Article
Multidisciplinary Sciences
Akane Morohoshi, Haruhiko Miyata, Keizo Tokuhiro, Rie Iida-Norita, Taichi Noda, Yoshitaka Fujihara, Masahito Ikawa
Summary: Spermatozoa undergo the acrosome reaction before fusing with eggs, and the molecular mechanism of this reaction involving calcium ion (Ca2+) remains unclear. Ferlin proteins, including Fer1l5, have C2 domains that bind to Ca2+. In this study, Fer1l5 was found to be essential for male fertility, as mutant spermatozoa lacking Fer1l5 were unable to undergo the acrosome reaction even with the use of a Ca2+ ionophore. These findings suggest that FER1L5 acts as the missing link between Ca2+ and the acrosome reaction.
Article
Obstetrics & Gynecology
Sohei Kuribayashi, Shinichiro Fukuhara, Go Tsujimura, Takahiro Imanaka, Koichi Okada, Norichika Ueda, Kentaro Takezawa, Hiroshi Kiuchi, Shigeyoshi Saito, Yusuke Takahashi, Hidetaka Kioka, Seiya Oura, Keisuke Shimada, Masahito Ikawa, Norio Nonomura
Summary: Chemical exchange saturation transfer (CEST) imaging can be used to assess testicular maturity and is important for evaluating the therapeutic effect of microscopic testicular sperm extraction.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2023)
Article
Obstetrics & Gynecology
Yuki Oyama, Haruhiko Miyata, Keisuke Shimada, Tamara Larasati, Yoshitaka Fujihara, Masahito Ikawa
Summary: Tulp2 deletion leads to abnormal tail morphology, impaired sperm motility, and male infertility in mice. Further microscopic observation reveals that the deletion affects the structure of outer dense fibers (ODFs), while no overt abnormalities are found in the formation of the mitochondrial sheath.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2022)