Dataset Information

CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

ABSTRACT: Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.

SUBMITTER: Zheng H

PROVIDER: S-EPMC10955179 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

Zheng Huimei H Gong Chenjia C Li Jingping J Hou Jiaru J Gong Xinhan X Zhu Xinhai X Deng Huan H Wu Haoyue H Zhang Fengbin F Shi Qinghua Q Zhou Jianteng J Shi Baolu B Yang Xiaohang X Xi Yongmei Y

Journal of cellular and molecular medicine 20240401 7

Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one ...[more]

PMID: 38509755

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Project description:Study questionCould sperm and leukocyte telomere length (TL) be associated with sperm quality parameters and reproductive health in men from the general population?Summary answerA positive association between sperm and leukocyte TL with sperm concentration and total count has been demonstrated.What is known alreadyMale factors account for almost half of cases of couple infertility, and shorter TLs have been observed in sperm from men with impaired sperm parameters. However, evidence in men from the general population is limited.Study design size durationA total of 200 volunteers of reproductive age were recruited between February 2021 and April 2023 to participate in the Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study.Participants/materials setting methodsTLs in sperm and leukocytes were measured using quantitative polymerase chain reaction (qPCR) in 168 and 194 participants, respectively. Sperm parameters, including concentration, total count, motility, vitality, and morphology, were analyzed using a computer-assisted sperm analysis (CASA) SCA® system according to the World Health Organization (WHO) 2010 guidelines. Multivariable regression models were performed to assess the associations between sperm and leukocyte TL, either in tertiles or as continuous variables, and sperm quality parameters while adjusting for potential confounders.Main results and the role of chanceParticipants in tertiles 2 (T2) and 3 (T3) of sperm TL showed a higher sperm concentration (β: 1.09; 95% CI: 0.09-2.09 and β: 2.06; 95% CI: 1.04-3.09 for T2 and T3, respectively; P-trend < 0.001), compared to those in the reference tertile (T1). Participants in the highest tertile of sperm TL showed higher total sperm count (β: 3.83; 95% CI: 2.08-5.58 for T3 vs T1; P-trend < 0.001). Participants in the top tertile of leukocyte TL showed higher sperm concentration (β: 1.49; 95% CI: 0.44-2.54 for T3 vs T1; P-trend = 0.004), and total count (β: 3.49; 95% CI: 1.62-5.35 for T3 vs T1; P-trend < 0.001) compared with participants in T1. These results remained consistent when sperm and leukocyte TL were modelled as continuous variables.Limitations reasons for cautionOne limitation is the impossibility of establishing a cause-effect relationship due to the cross-sectional study design. Additionally, the sample size of the study cannot be considered large.Wider implications of the findingsSperm and leukocyte TLs are associated with sperm quality parameters in the general population. Additional determinations and further studies with larger sample sizes are needed to clarify the mechanisms underlying these associations and to investigate the further implications.Study funding/competing interestsThe Led-Fertyl study was supported by the Spanish government's official funding agency for biomedical research, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS) and co-funded by the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' (PI21/01447), and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S., senior author of the present study, is partially supported by ICREA under the ICREA Academia program. M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI_B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). All authors declare that they have no conflicts of interest.Trial registration numberN/A.

Dataset Information

CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

Publications

CCDC157 is essential for sperm differentiation and shows oligoasthenoteratozoospermia-related mutations in men.

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