Impact of Advanced Paternal Age on Fertility and Risks of Genetic Disorders in Offspring

Author:

Kaltsas Aris1ORCID,Moustakli Efthalia2,Zikopoulos Athanasios1,Georgiou Ioannis2,Dimitriadis Fotios3ORCID,Symeonidis Evangelos N.3ORCID,Markou Eleftheria4,Michaelidis Theologos M.56ORCID,Tien Dung Mai Ba7ORCID,Giannakis Ioannis1ORCID,Ioannidou Eleni Maria8,Papatsoris Athanasios9,Tsounapi Panagiota10,Takenaka Atsushi10,Sofikitis Nikolaos1,Zachariou Athanasios1ORCID

Affiliation:

1. Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece

2. Laboratory of Medical Genetics in Clinical Practice, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece

3. Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece

4. Department of Microbiology, University Hospital of Ioannina, 45500 Ioannina, Greece

5. Department of Biological Applications and Technologies, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece

6. Biomedical Research Institute, Foundation for Research and Technology-Hellas, 45500 Ioannina, Greece

7. Department of Andrology, Binh Dan Hospital, Ho chi Minh City 70000, Vietnam

8. Dental Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria

9. 2nd Department of Urology, School of Medicine, Sismanoglio Hospital, National and Kapodistrian Univesity of Athens, 15126 Athens, Greece

10. Division of Urology, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan

Abstract

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father’s age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father’s age contributes to his offspring’s higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father’s advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father’s advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring’s diseases is crucial, so that they can be effectively guided through their reproductive years.

Publisher

MDPI AG

Subject

Genetics (clinical),Genetics

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