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Germline deletion of Cdyl causes teratozoospermia and progressive infertility in male mice.

ABSTRACT: Chromodomain Y (CDY) is one of the candidate genes for male dyszoospermia related to Y chromosome microdeletion (YCM). However, the function of CDY in regulating spermatogenesis has not been completely determined. The mouse Cdyl (CDY-like) gene is the homolog of human CDY. In the present study, we generated a germline conditional knockout (cKO) model of mouse Cdyl. Significantly, the Cdyl^cKO male mice suffered from the defects in spermatogonia maintenance and spermatozoon morphogenesis, demonstrating teratozoospermia and a progressive infertility phenotype in early adulthood. Importantly, patterns of specific histone methylation and acetylation were extensively changed, which disturbed the transcriptome in Cdyl^cKO testis. Our findings indicated that Cdyl is crucial for spermatogenesis and male fertility, which provides novel insights into the function of CDY gene, as well as the pathogenesis of YCM-related reproductive failure.

SUBMITTER: Xia X

PROVIDER: S-EPMC6408431 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Germline deletion of Cdyl causes teratozoospermia and progressive infertility in male mice.

Xia Xiaoyu X Zhou Xiaowei X Quan Yanmei Y Hu Yanqin Y Xing Fengying F Li Zhengzheng Z Xu Bufang B Xu Chen C Zhang Aijun A

Cell death & disease 20190308 3

Chromodomain Y (CDY) is one of the candidate genes for male dyszoospermia related to Y chromosome microdeletion (YCM). However, the function of CDY in regulating spermatogenesis has not been completely determined. The mouse Cdyl (CDY-like) gene is the homolog of human CDY. In the present study, we generated a germline conditional knockout (cKO) model of mouse Cdyl. Significantly, the Cdyl<sup>cKO</sup> male mice suffered from the defects in spermatogonia maintenance and spermatozoon morphogenesi ...[more]

PMID: 30850578

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Project description:Background and objectiveBasic semen analysis is the first step in the evaluation of male infertility. It includes an assessment of sperm morphology which is believed to reflect on overall spermatogenesis and sperm function. Teratozoospermia, defined as abnormal sperm morphology, is frequently present in association with severe oligoasthenozoospermia, but isolated teratozoospermia (in the presence of normal counts and motility) is a poorly understood clinical entity with conflicting implications in terms of fertility potential and treatment strategies. The following paper aims to: (I) discuss the classification of sperm morphology, causes, and molecular mechanism of teratozoospermia; (II) analyze the clinical significance and potential treatment options of isolated teratozoospermia as a cause of male infertility and a predictor of fertility outcome; and (III) provide a SWOT (strengths, weaknesses, opportunities, and threats) analysis based on the existing literature on this topic.MethodsA comprehensive search from database inception to 25 April 2023 was conducted in PubMed for relevant papers relating to isolated teratozoospermia in male infertility. Finally, seven systematic reviews/reviews/meta-analyses and 81 original articles were synthesized into the current narrative review.Key content and findingsClassification of sperm morphology has evolved significantly since the first edition of the World Health Organization (WHO) Manual of Human Semen Analysis. Kruger's strict criteria are the most used classification and have been shown to correlate with fertility outcomes. There are many causes of teratozoospermia including genetic and environmental factors and physical conditions like varicocele. Teratozoospermia correlates with sperm DNA damage, elevated oxidative stress, low antioxidant function, and apoptotic alterations, which can result in impaired spermatozoa function and lower pregnancy rates. However, the clinical correlation between teratozoospermia and assisted reproductive technology (ART) outcome shows conflicting data with recent meta-analyses suggesting that isolated teratozoospermia was not associated with poor fertility outcomes from ART and that intrauterine insemination (IUI) can be an effective option even in the presence of teratozoospermia. There is very limited data on effective therapeutic options to treat idiopathic isolated teratozoospermia. The opportunity for future research is huge to fill the gap in the medical literature on this topic.ConclusionsContemporary literature on isolated teratozoospermia shows conflicting results in terms of its actual clinical implication in male infertility and the utility of available treatment options. Further research is warranted on this clinical entity to improve sperm function and future paternity.

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Germline deletion of Cdyl causes teratozoospermia and progressive infertility in male mice.

Publications

Germline deletion of Cdyl causes teratozoospermia and progressive infertility in male mice.

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