Ovarian follicle ageing

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• ???
• 2008/05/16

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Ovarian follicle ageing

• The biologic capacity of a woman to reproduce
  drops after a peak of efficiency in the early 20s
• Save women from the risk associated with
  pregnancy and birth delivery in advanced age
• Maximize the length of time during which they can
  bear children

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Ageing of the follicle pool

• Apoptosis is the driving force behind follicle
  loss with ageing
• Specific age-related morphological changes
• Mitochondria in granulosacells
• Serum FSH levels

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Unhealthy status of aged oocyte

• Human oocyte aneuploidy increases with age
• Ooplasmic aging and nuclear morphological changes
• Impaired accumulation of maternal RNA
• Genetic and function flaws in mitochondria
• Compromised meiotic clock
• Precocious post-ovulatory ageing
• Telomere shortening

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Compromised microenvironment

• Paracrine regulators of follicular development
• Follicular fluid meiosis activating sterol
  (FF-MAS)
• VEGF levels
• Perifollicular vascularization Costello et
  al., 2006

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Oxidative stress

• Production of ROS by mitochondria
• Enzymatic or non-enzymatic antioxidant defense
• Primordial and periovulatory follicles suffered
  from age-related oxidative stress and impaired
  enzymatic antioxidant defense
• Controversial results in the correlation between
  IVF outcomes and follicular fluid ROS levels

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Hypoxia

• Both hypoxic and hyperoxic conditions can be
  responsible for oxidative stress
• Formation of ROS can be directly caused by
  hypoxia or indirectly after reoxygenation
• Mitochondria of granulosa cells from aged women
  exhibit similar structure damage to those in
  cells exposed to hypoxia

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Protein glycosylation

• Advanced glycation endproducts (AGEs) universal
  symptoms of ageing
• AGEs cause tissue injury by protein cross-linking
  or binding to specific receptors
• Collagen are most vulnerable to cross-linking
• Receptor of AGE (RAGE) is highly expressed in
  granulosa cells, theca interna, endothelial and
  stromal cells

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