Differential sperm histone retention in normozoospermic ejaculates of infertile men negatively affects sperm functional competence and embryo quality

Author:

Pandya Riddhi Kirit1,Jijo Ameya1,Cheredath Aswathi1,Uppangala Shubhashree2,Salian Sujith Raj1,Lakshmi Vani R3,Kumar Pratap4,Kalthur Guruprasad5ORCID,Gupta Sanjay6,Adiga Satish Kumar1ORCID

Affiliation:

1. Centre of Excellence in Clinical Embryology Department of Reproductive Science Kasturba Medical College Manipal Academy of Higher Education Manipal India

2. Division of Reproductive Genetics Department of Reproductive Science Kasturba Medical College Manipal Academy of Higher Education Manipal India

3. Department of Data Science Prasanna School of Public Health Manipal Academy of Higher Education Manipal India

4. Department of Reproductive Medicine and Surgery Kasturba Medical College Manipal Academy of Higher Education Manipal India

5. Division of Reproductive Biology Department of Reproductive Science Kasturba Medical College Manipal Academy of Higher Education Manipal India

6. KS313 Epigenetics and Chromatin Biology Group Gupta Lab, Cancer Research Institute Advanced Centre for Treatment Research and Education in Cancer Tata Memorial Centre Navi Mumbai India

Abstract

AbstractBackgroundThe unique epigenetic architecture that sperm cells acquire during spermiogenesis by retaining <15% of either canonical or variant histone proteins in their genome is essential for normal embryogenesis. Whilst heterogeneous levels of retained histones are found in morphologically normal spermatozoa, their effect on reproductive outcomes is not fully understood.MethodsProcessed spermatozoa (n = 62) were tested for DNA integrity by sperm chromatin dispersion assay, and retained histones were extracted and subjected to dot‐blot analysis. The impact of retained histone modifications in normozoospermic patients on sperm functional characteristics, embryo quality, metabolic signature in embryo spent culture medium and pregnancy outcome was studied.ResultsDot‐blot analysis showed heterogeneous levels of retained histones in the genome of normozoospermic ejaculates. Post‐wash sperm yield was affected by an increase in H3K27Me3 and H4K20Me3 levels in the sperm chromatin (p < 0.05). Also, spermatozoa with higher histone H3 retention had increased DNA damage (p < 0.05). Spermatozoa from these cohorts, when injected into donor oocytes, correlated to a significant decrease in the fertilisation rate with an increase in sperm histone H3 (p < 0.05) and H3K27Me3 (p < 0.01). An increase in histone H3 negatively affected embryo quality (p < 0.01) and clinical pregnancy outcome post‐embryo transfer (p < 0.05). On the other hand, spent culture medium metabolites assessed by high‐resolution (800 MHz) nuclear magnetic resonance showed an increased intensity of the amino acid methionine in the non‐pregnant group than in the pregnant group (p < 0.05) and a negative correlation with sperm histone H3 in the pregnant group (p < 0.05).Discussion and conclusionHistone retention in spermatozoa can be one of the factors behind the development of idiopathic male infertility. Such spermatozoa may influence embryonic behaviour and thereby affect the success rate of assisted reproductive technology procedures. These results, although descriptive in nature, warrant further research to address the underlying mechanisms behind these clinically important observations.

Funder

Indian Council of Medical Research

Publisher

Wiley

Subject

Urology,Endocrinology,Reproductive Medicine,Endocrinology, Diabetes and Metabolism

Reference85 articles.

1. The chromosomes in heredity;Sutton WS;Biol Bull,1903

2. The biology of the sperm cell;Baccetti B;Monogr Dev Biol,1976

3. Centrioles at the beginning of human development;Sathananthan AH;Proc Natl Acad Sci U S A,1991

4. PLC zeta: a sperm‐specific trigger of Ca (2+) oscillations in eggs and embryo development;Saunders CM;Development,2002

5. Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility;Castillo J;Asian J Androl,2015

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3