Proteostasis, Assisted Reproductive Technologies, and Neurodevelopmental Differences: An Integrative Perspective.

Area of Science:

• Cellular Biology
• Reproductive Science
• Developmental Neuroscience

Background:

• Proteostasis, the regulation of protein synthesis, folding, trafficking, and degradation, is critical for cellular integrity and development.
• Efficient proteostasis is essential for reproductive success, including gamete quality, fertilization, embryonic development, and neurodevelopment.
• Impaired proteostasis is increasingly linked to infertility and potential vulnerabilities associated with assisted reproductive technologies [ARTs].

Purpose of the Study:

• To provide an integrative perspective on the role of disrupted proteostasis in infertility, ART procedures, and neurodevelopmental differences [NDDs].
• To review evidence linking proteostasis failure to male and female infertility, focusing on molecular chaperones like heat shock protein 60 [Hsp60].
• To highlight the impact of ART on epigenetic reprogramming and proteostasis during early embryogenesis, affecting neurodevelopmental outcomes.

Main Methods:

• Review of epidemiological and molecular findings on proteostasis failure in infertility.
• Emphasis on the role of molecular chaperones, particularly heat shock protein 60 [Hsp60].
• Discussion of proteoforms, proteome complexity, and potential biomarkers for ART optimization.

Main Results:

• Proteostasis failure is implicated in both male and female infertility.
• Heat shock protein 60 [Hsp60] is a key mediator of mitochondrial function, protein quality control, and reproductive competence.
• ART procedures may disrupt proteostasis and epigenetic stability, influencing neurodevelopmental outcomes.
• Proteomic and chaperone-based biomarkers show potential for improving ART strategies and risk assessment.

Conclusions:

• Proteostasis is a fundamental mechanism linking reproductive biology, ART outcomes, and long-term neurodevelopment.
• Disruptions in proteostasis during ART may contribute to neurodevelopmental differences.
• Further translational research is needed to leverage proteomic and chaperone insights for optimizing ART and assessing risks.