DNA repair and response to sperm DNA damage in oocytes and embryos, and the potential consequences in ART: a systematic review

Author:

Newman H1ORCID,Catt S1ORCID,Vining B23,Vollenhoven B145,Horta F14ORCID

Affiliation:

1. Education Program in Reproduction and Development, Department of Obstetrics and Gynecology, Monash University, Melbourne, VIC, Australia

2. Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Melbourne, VIC, Australia

3. Department of Molecular and Translational Science, Monash University, Melbourne, VIC, Australia

4. Monash IVF, Melbourne, VIC, Australia

5. Women’s and Newborn Program, Monash Health, VIC, Australia

Abstract

Abstract Sperm DNA damage is considered a predictive factor for the clinical outcomes of patients undergoing ART. Laboratory evidence suggests that zygotes and developing embryos have adopted specific response and repair mechanisms to repair DNA damage of paternal origin. We have conducted a systematic review in accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) to identify and review the maternal mechanisms used to respond and repair sperm DNA damage during early embryonic development, how these mechanisms operate and their potential clinical implications. The literature search was conducted in Ovid MEDLINE and Embase databases until May 2021. Out of 6297 articles initially identified, 36 studies were found to be relevant through cross referencing and were fully extracted. The collective evidence in human and animal models indicate that the early embryo has the capacity to repair DNA damage within sperm by activating maternally driven mechanisms throughout embryonic development. However, this capacity is limited and likely declines with age. The link between age and decreased DNA repair capacity could explain decreased oocyte quality in older women, poor reproductive outcomes in idiopathic cases and patients who present high sperm DNA damage. Ultimately, further understanding mechanisms underlying the maternal repair of sperm DNA damage could lead to the development of targeted therapies to decrease sperm DNA damage, improved oocyte quality to combat incoming DNA insults or lead to development of methodologies to identify individual spermatozoa without DNA damage.

Funder

Education Program of Reproduction and Development (EPRD), Department of Obstetrics and Gynaecology, School of Clinical Science, Monash University

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Obstetrics and Gynecology,Genetics,Molecular Biology,Embryology,Reproductive Medicine

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