Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice

Hua, Juan; Xu, Bo; Liu, Wenjing; Shi, JingTian; Jiang, Hui; Zha, Xiaojun; Zhang, Xiansheng; Wan, Yangyang

doi:10.1093/hmg/ddad061

Cited by 7 publications

(2 citation statements)

References 46 publications

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“…Infertility is a major health issue worldwide, affecting approximately 8-12% of couples in the reproductive age group who are unable to conceive at least once after 12 months or more of regular unprotected sexual intercourse [1,2]. Overall, infertility affects up to 80 million people worldwide, with 50% being due to male-infertility-associated factors related to abnormal semen parameters [3,4]. Sperm count, percentage of motile sperm and abnormal sperm morphology in the ejaculate are used to determine semen quality [3].…”

Section: Introductionmentioning

confidence: 99%

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men

Dhillon,

Shahid,

Deo

et al. 2024

IJMS

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Infertility affects millions of couples worldwide and has a profound impact not only on their families, but also on communities. Telomere attrition has been associated with infertility, DNA damage and fragmentation. Oxidative stress has been shown to affect sperm DNA integrity and telomere length. Sirtuins such as SIRT1 and SIRT3 are involved in aging and oxidative stress response. The aim of the present study is to determine the role of SIRT1 and SIRT3 in regulating oxidative stress, telomere shortening, and their association with oligospermia. Therefore, we assessed the protein levels of SIRT1 and SIRT3, total antioxidant capacity (TAC), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase activity (CAT) in the seminal plasma of 272 patients with oligospermia and 251 fertile men. We also measured sperm telomere length (STL) and leukocyte telomere length (LTL) using a standard real-time quantitative PCR assay. Sperm chromatin and protamine deficiency were also measured as per standard methods. Our results for oligospermic patients demonstrate significant reductions in semen parameters, shorter STL and LTL, lower levels of SOD, TAC, CAT, SIRT1 and SIRT3 levels, and also significant protamine deficiency and higher levels of MDA and DNA fragmentation. We conclude that a shorter TL in sperms and leukocytes is associated with increased oxidative stress that also accounts for high levels of DNA fragmentation in sperms. Our results support the hypothesis that various sperm parameters in the state of oligospermia are associated with or caused by reduced levels of SIRT1 and SIRT3 proteins.

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Section: Introductionmentioning

confidence: 99%

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men

Dhillon,

Shahid,

Deo

et al. 2024

IJMS

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“…To understand how the BB architecture enables force resistance, we studied the conserved BB stability and disease-related protein, Poc1 (Pearson et al, 2009a; Li et al, 2021; Beck et al, 2014; Hua et al, 2023). Poc1 is necessary for centriole integrity and enables BBs to resist mechanical forces from beating cilia.…”

Section: Introductionmentioning

confidence: 99%

Poc1 is a basal body inner junction protein that promotes triplet microtubule integrity and interconnections

Ruehle,

Li,

Agard

et al. 2023

Preprint

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Basal bodies (BBs) are conserved eukaryotic structures that organize motile and primary cilia. The BB is comprised of nine, cylindrically arranged, triplet microtubules (TMTs) that are connected to each other by inter-TMT linkages which maintain BB structure. During ciliary beating, forces transmitted to the BB must be resisted to prevent BB disassembly. Poc1 is a conserved BB protein important for BBs to resist ciliary forces. To understand how Poc1 confers BB stability, we identified the precise position of Poc1 binding in theTetrahymenaBB and the effect of Poc1 loss on BB structure. Poc1 binds at the TMT inner junctions, stabilizing TMTs directly. From this location, Poc1 also stabilizes inter-TMT linkages throughout the BB, including the cartwheel pinhead and the inner scaffold. Moreover, we identify a molecular response to ciliary forces via a molecular remodeling of the inner scaffold, as determined by differences in Fam161A localization. Thus, while not essential for BB assembly, Poc1 promotes BB interconnections that establish an architecture competent to resist ciliary forces.

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Abnormal centriolar biomarker ratios correlate with unexplained bull artificial insemination subfertility: a pilot study

Turner,

Achinger,

Kong

et al. 2023

Sci Rep

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The mechanisms underlying male infertility are poorly understood. Most mammalian spermatozoa have two centrioles: the typical barrel-shaped proximal centriole (PC) and the atypical fan-like distal centriole (DC) connected to the axoneme (Ax). These structures are essential for fertility. However, the relationship between centriole quality and subfertility (reduced fertility) is not well established. Here, we tested the hypothesis that assessing sperm centriole quality can identify cattle subfertility. By comparing sperm from 25 fertile and 6 subfertile bulls, all with normal semen analyses, we found that unexplained subfertility and lower sire conception rates (pregnancy rate from artificial insemination in cattle) correlate with abnormal centriolar biomarker distribution. Fluorescence-based Ratiometric Analysis of Sperm Centrioles (FRAC) found only four fertile bulls (4/25, 16%) had positive FRAC tests (having one or more mean FRAC ratios outside of the distribution range in a group’s high-quality sperm population), whereas all of the subfertile bulls (6/6, 100%) had positive FRAC tests (P = 0.00008). The most sensitive biomarker was acetylated tubulin, which had a novel labeling pattern between the DC and Ax. These data suggest that FRAC and acetylated tubulin labeling can identify bull subfertility that remains undetected by current methods and may provide insight into a novel mechanism of subfertility.

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Homozygous frameshift variant in POC1B causes male infertility with oligoasthenoteratozoospermia in human and mice

Cited by 7 publications

References 46 publications

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men

Reduced SIRT1 and SIRT3 and Lower Antioxidant Capacity of Seminal Plasma Is Associated with Shorter Sperm Telomere Length in Oligospermic Men

Poc1 is a basal body inner junction protein that promotes triplet microtubule integrity and interconnections

Abnormal centriolar biomarker ratios correlate with unexplained bull artificial insemination subfertility: a pilot study

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