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
Multidisciplinary Sciences
Wei Zheng, Fan Li, Zhanyu Ding, Hao Liu, Lei Zhu, Cong Xu, Jiawei Li, Qi Gao, Yanxing Wang, Zhenglin Fu, Chao Peng, Xiumin Yan, Xueliang Zhu, Yao Cong
Summary: In this study, the researchers found that the murine radial spoke (RS) head is compositionally distinct from that of Chlamydomonas, and the core complex contacts the central pair (CP) projections either rigidly or elastically for optimized RS-CP interactions and mechanosignal transduction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Obstetrics & Gynecology
Lydia Newman, Jagrati Chopra, Claire Dossett, Elizabeth Shepherd, Amelia Bercusson, Mary Carroll, Woolf Walker, Jane S. Lucas, Ying Cheong
Summary: This review aimed to summarize the prevalence of subfertility, possible underlying mechanisms, and the success of ART in men and women with PCD. Limited evidence suggests subfertility in affected individuals is likely caused by abnormal cilia motion in the fallopian tubes, endometrium and efferent ductules, and dysmotile sperm. Some men and women with PCD benefited from ART, which suggests its use should be considered in the management of subfertility in this patient group.
HUMAN REPRODUCTION UPDATE
(2023)
Article
Genetics & Heredity
Yunhao Li, Yong Li, Ying Wang, Lanlan Meng, Chen Tan, Juan Du, Yue-Qiu Tan, Hongchuan Nie, Qianjun Zhang, Guangxiu Lu, Ge Lin, Huanzhu Li, Huan Zhang, Chaofeng Tu
Summary: The genetic cause of primary ciliary dyskinesia (PCD) and male infertility in two unrelated Han Chinese families was identified through whole-exome sequencing. Variants in the LRRC6 gene were found in two patients with PCD and male infertility. The LRRC6-mutant spermatozoa showed abnormal morphology and ultrastructure, and the LRRC6 protein levels were significantly decreased. Interestingly, both patients were able to conceive through ICSI and gave birth to healthy babies.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2023)
Article
Genetics & Heredity
Chaofeng Tu, Jiangshan Cong, Qianjun Zhang, Xiaojin He, Rui Zheng, Xiaoxuan Yang, Yang Gao, Huan Wu, Mingrong Lv, Yayun Gu, Shuai Lu, Chunyu Liu, Shixiong Tian, Lanlan Meng, Weili Wang, Chen Tan, Hongchuan Nie, Dongyan Li, Huan Zhang, Fei Gong, Liang Hu, Guangxiu Lu, Wenming Xu, Ge Lin, Feng Zhang, Yunxia Cao, Yue-Qiu Tan
Summary: Research has identified the crucial role of bi-allelic DNAH10 variants in causing asthenoteratozoospermia with MMAF in males, leading to flagellar assembly defects in sperm. This finding provides guidance for genetic counseling related to MMAF and offers important insights into the diagnosis of this condition.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Rongchun Wang, Danhui Yang, Ting Guo, Cheng Lei, Xu Chen, Xi Kang, Jie Qing, Hong Luo
Summary: A novel homozygous variant in ODAD3, c.1166_1169dupAGAC, p.(Leu391Aspfs*105), was identified in a Chinese family with PCD through exome and Sanger sequencing. This frameshift variant was predicted to be disease-causing, expanding the genetic spectrum and clinical phenotypes of ODAD3 variants in PCD, providing potential evidence for future genetic counseling and gene-targeted therapy.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Xinyue Zhao, Haijun Ge, Wenshuai Xu, Chongsheng Cheng, Wangji Zhou, Yan Xu, Junping Fan, Yaping Liu, Xinlun Tian, Kai-Feng Xu, Xue Zhang
Summary: This study identified novel CFAP54 pathogenic variants in PCD patients and validated their pathogenicity through mouse models. The study is of great significance for expanding the gene spectrum associated with PCD and improving future genetic testing.
FRONTIERS OF MEDICINE
(2023)
Article
Medicine, General & Internal
Andrea Felsoova, Tibor Sloboda, Lukas Hudec, Miroslav Koblizek, Petr Pohunek, Vendula Martinu, Zofia Varenyiova, Simona Kadlecova, Jiri Uhlik
Summary: The ciliary ultrastructure can be damaged in various situations, leading to genetic diseases like primary ciliary dyskinesia (PCD) and acquired conditions like secondary ciliary dyskinesia (SCD). The diagnosis of these diseases is complex and requires multiple methods, including evaluation of the ciliary ultrastructure. While current programs for automatic quantitative analysis of cilia have limitations, there is great potential for automatic analysis of the ciliary ultrastructure in the future.
Article
Medicine, General & Internal
Noemie Bricmont, Romane Bonhiver, Lionel Benchimol, Bruno Louis, Jean-Francois Papon, Justine Monseur, Anne-Francoise Donneau, Catherine Moermans, Florence Schleich, Doriane Calmes, Anne-Lise Poirrier, Renaud Louis, Marie-Christine Seghaye, Celine Kempeneers
Summary: In this study, we evaluated the effects of delay after sampling and the temperature for conservation of respiratory ciliated samples on assessments of ciliary beating. We found that ciliary beating can be evaluated at 37 degrees Celsius up to 9 hours after nasal brushing, but the storage temperature can modify ciliary beating.
Article
Genetics & Heredity
Isabella Aprea, Johanna Raidt, Inga Marlena Hoeben, Niki Tomas Loges, Tabea Noethe-Menchen, Petra Pennekamp, Heike Olbrich, Thomas Kaiser, Luisa Biebach, Frank Tuettelmann, Judit Horvath, Maria Schubert, Claudia Krallmann, Sabine Kliesch, Heymut Omran
Summary: Male fertility issues worldwide may be caused by defects in the preassembly of outer and inner dynein arms, leading to abnormal sperm flagella, impaired sperm motility, and infertility. Studying sperm cells of individuals with mutations in genes related to this process helps understand the clinical relevance of preassembly of dynein arms on male fertility.
Article
Medicine, General & Internal
Mohammed T. Alsamri, Amnah Alabdouli, Durdana Iram, Alia M. Alkalbani, Ayesha S. Almarzooqi, Abdul-Kader Souid, Ranjit Vijayan
Summary: Primary ciliary dyskinesia (PCD) is a poorly understood autosomal recessive disorder prevalent in tribal communities of the United Arab Emirates. This retrospective study aimed to assess the pathogenicity of genetic variants associated with PCD in indigenous patients, identifying novel variants related to specific clinical manifestations. Further research is necessary to fully comprehend the genetic underpinnings of PCD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Cell Biology
Peiwei Liu, Ying Liu, Jun Zhou
Summary: Cilia are surface-exposed organelles that provide motility and sensory functions for cells, and it is widely believed that mechanosensation can be mediated through cilia. Polycystin-1 and -2 (PC-1 and PC-2, respectively) are transmembrane proteins that can localize to cilia; however, the molecular mechanisms by which polycystins contribute to mechanosensation are still controversial.
JOURNAL OF CELL SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Lance Lee, Lawrence E. Ostrowski
Summary: Over the past two decades, our understanding of motile cilia and their role in disease has greatly increased, with critical information and insight coming from the analysis of mouse models. Mouse models have made significant contributions to genetic and cell biological studies of motile cilia, and have been at the forefront of research on mammalian motile cilia and PCD pathogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Obstetrics & Gynecology
Daijuan Chen, Yan Liang, Juan Lie, Xueguang Zhang, Rui Zheng, Xiaodong Wang, Heng Zhang, Ying Shen
Summary: This study identified a novel homozygous mutation in CCDC39 in two siblings affected by a typical PCD phenotype, with one of them being infertile due to MMAF. The mutation in CCDC39 was found to be associated with the pathogenesis of PCD and MMAF, with successful outcomes from ICSI treatment. This novel variant of CCDC39 contributes to the genetic diagnosis, counseling, and treatment of male infertility in PCD patients with the MMAF phenotype.
REPRODUCTIVE BIOMEDICINE ONLINE
(2021)
Article
Cell Biology
Yi Tian Yap, Wei Li, Qi Zhou, Sarah Haj-Diab, Dipanwita Dutta Chowdhury, Asmita Vaishnav, Pamela Harding, David C. Williams, Brian F. Edwards, Jerome F. Strauss, Zhibing Zhang
Summary: SPAG6 and SPAG6L are proteins with different functions, playing important roles in sperm generation, hearing, and immunological synapse.
Article
Biochemistry & Molecular Biology
P. Sipila, A. Junnila, J. Hakkarainen, R. Huhtaniemi, L. Mairinoja, F. P. Zhang, L. Strauss, C. Ohlsson, N. Kotaja, I. Huhtaniemi, M. Poutanen
Review
Obstetrics & Gynecology
Christiane Pleuger, Mari S. Lehti, Jessica E. M. Dunleavy, Daniela Fietz, Moira K. O'Bryan
HUMAN REPRODUCTION UPDATE
(2020)
Article
Biochemistry & Molecular Biology
Ram Prakash Yadav, Juho-Antti Makela, Hanna Hyssala, Sheyla Cisneros-Montalvo, Noora Kotaja
NUCLEIC ACIDS RESEARCH
(2020)
Article
Multidisciplinary Sciences
Juho-Antti Makela, Sheyla Cisneros-Montalvo, Tiina Lehtiniemi, Opeyemi Olotu, Hue M. La, Jorma Toppari, Robin M. Hobbs, Martti Parvinen, Noora Kotaja
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2020)
Article
Biochemistry & Molecular Biology
Andreas Werner, James E. Clark, Calum Samaranayake, John Casement, Hany S. Zinad, Shaymaa Sadeq, Surar Al-Hashimi, Martin Smith, Noora Kotaja, John S. Mattick
Summary: The transcriptome of testis is highly complex, with distinct patterns of dsRNA formation compared to liver, and is significantly less complex in juvenile mice. Genes generating dsRNA are significantly expressed in male germ cells and show enrichment in pachytene spermatocytes, with a lower formation rate on sex chromosomes. Testis dsRNAs are associated with natural antisense genes, contributing to a testis-specific mechanism involving the RNA interference pathway.
Letter
Oncology
Jamie Heather Oakley, Dean R. Campagna, Liang Sun, Shira Rockowitz, Piotr Sliz, Jeanne Boudreaux, Gary Woods, Mark D. Fleming
PEDIATRIC BLOOD & CANCER
(2022)
Article
Immunology
Ines Felix, Heli Jokela, Joonas Karhula, Noora Kotaja, Eriika Savontaus, Marko Salmi, Pia Rantakari
Summary: This study reveals the diversity and developmental origin of resident adipose tissue macrophages through comprehensive single-cell mass cytometry analysis, as well as the functional differences in their in vitro and in vivo activities. A high-fat diet induces changes in the quantity and functionality of macrophages, which can be reversed by dietary intervention.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Luis Crisostomo, Matthieu Bourgery, Luis Rato, Joao F. Raposo, Rachel L. Batterham, Noora Kotaja, Marco G. Alves
Summary: Excessive adiposity caused by high-fat diets may affect testicular metabolism and function in future generations through the influence of sperm small non-coding RNA.
Article
Biochemistry & Molecular Biology
Tiina Lehtiniemi, Matthieu Bourgery, Lin Ma, Ammar Ahmedani, Margareeta Makela, Juho Asteljoki, Opeyemi Olotu, Samuli Laasanen, Fu-Ping Zhang, Kun Tan, Jennifer N. Chousal, Dana Burow, Satu Koskinen, Asta Laiho, Laura L. Elo, Frederic Chalmel, Miles F. Wilkinson, Noora Kotaja
Summary: This study demonstrates that SMG6 is essential for male germ cell differentiation in mice, and its loss leads to transcriptome misregulation and arrest of spermatogenesis. SMG6 is enriched in the chromatoid body and may function together with the piRNA pathway to co-regulate genes in round spermatids.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Developmental Biology
Ram Prakash Yadav, Sini Leskinen, Lin Ma, Juho-Antti Makela, Noora Kotaja
Summary: Proper regulation of heterochromatin is crucial for spermatogenesis. This study reveals the dynamic localization patterns of chromatin regulators and disrupted sex chromatin status in spermatocytes without DICER. Heterochromatin is dynamically formed and organized in differentiating male germ cells, and its regulation is essential for normal spermatogenesis.
Article
Andrology
Opeyemi Olotu, Mark Dowling, David Homolka, Magdalena N. Wojtas, Panyi Tran, Tiina Lehtiniemi, Matteo Da Ros, Ramesh S. Pillai, Noora Kotaja
Summary: In this study, the function of the intermitochondrial cement (IMC) in piRNA biogenesis was clarified by identifying proteins that form complexes with PIWIL2/MILI. The two identified proteins, EXD1 and EXD2, were found to be involved in piRNA biogenesis and located in the IMC. Furthermore, the mutation of Exd2 exonuclease domain was shown to disrupt the regulation of specific pachytene piRNA clusters but not male fertility.
Article
Endocrinology & Metabolism
Oliver Meikar, Daniel Majoral, Olli Heikkinen, Eero Valkama, Sini Leskinen, Ana Rebane, Pekka Ruusuvuori, Jorma Toppari, Juho-Antti Makela, Noora Kotaja
Summary: Spermatogenesis is a complex differentiation process that occurs in the seminiferous tubules. A specific organization of spermatogenic cells within the seminiferous epithelium allows for synchronous progression of germ cells at certain stages of differentiation. To facilitate the analysis of spermatogenesis, researchers have developed a convolutional deep neural network-based approach called STAGETOOL. STAGETOOL accurately classifies histological images of DAPI-stained mouse testis cross-sections into different stage classes and cell categories. It has high classification accuracy and can be applied for analyzing spermatogenic defects in knockout mouse models and profiling protein expression patterns. STAGETOOL represents a major advancement in male reproductive biology research.
Article
Genetics & Heredity
Tiina Lehtiniemi, Margareeta Makela, Noora Kotaja
BEYOND OUR GENES: Pathophysiology of Gene and Environment Interaction and Epigenetic Inheritance
(2020)
Article
Endocrinology & Metabolism
Christiane Pleuger, Mari S. Lehti, Madeleine Cooper, Anne E. O'Connor, D. Jo Merriner, Ian M. Smyth, Denny L. Cottle, Daniela Fietz, Martin Bergmann, Moira K. O'Bryan
Article
Endocrinology & Metabolism
Imrul Faisal, Sheyla Cisneros-Montalvo, Geert Hamer, Minna M. Tuominen, Pirkka-Pekka Laurila, Manuela Tumiati, Matti Jauhiainen, Noora Kotaja, Jorma Toppari, Juho-Antti Makela, Liisa Kauppi