[Advanced paternal age-related germline mutations in the offspring with neurodevelopmental disorders: An update]

Area of Science:

• Reproductive Biology
• Developmental Neuroscience
• Genetics

Background:

• Childbirth at advanced maternal and paternal ages is increasing globally.
• Advanced paternal age (APA) is linked to adverse offspring health outcomes, including neurodevelopmental disorders (NDDs).
• Mechanisms may involve aging-related DNA damage and epigenetic alterations in male germ cells.

Purpose of the Study:

• To review the association between APA and NDDs in offspring.
• To explore potential biological mechanisms linking APA to NDDs.
• To highlight the need for advanced research into multifactorial causes.

Main Methods:

• Literature review of epidemiological data on NDDs.
• Examination of germline de novo mutations and their accumulation.
• Analysis of epigenetic modifications in spermatozoa.
• Review of existing univariate studies on APA and NDDs.

Main Results:

• APA is associated with an increased risk of NDDs in offspring.
• Potential contributing factors include germline mutations and epigenetic changes.
• Current research often employs limited univariate analytical approaches.

Conclusions:

• APA poses risks for offspring neurodevelopment.
• Multiple synergistic mechanisms likely contribute to APA-related NDDs.
• Further investigation into complex, multifactorial effects is crucial for diagnosis and treatment.