Роль сфинголипидного метаболизма в развитии нарушений репродуктивного здоровья женщин

Сфинголипиды представляют собой биоактивные липиды, регулирующие процессы пролиферации, дифференцировки, апоптоза, ангиогенеза и воспаления. В последние годы их роль в поддержании овариального резерва и развитии нарушений женской репродуктивной функции получила особое внимание. Церамиды (англ. ceramides, CERs) и сфингозин-1-фосфат (англ. sphingosine-1-phosphate, S1P) формируют динамический баланс между проапоптотическими и провыживательными сигналами, определяя судьбу фолликулов и ооцитов. Нарушения метаболизма сфинголипидов выявлены при раке яичников, синдроме поликистозных яичников, эндометриозе, ожирении, снижении овариального резерва и преждевременной недостаточности яичников. Эти состояния сопровождаются сдвигом соотношения CERs/S1P, что отражается на качестве ооцитов, их чувствительности к окислительному стрессу, химиотерапии и воспалению. Появляющиеся данные показывают, что таргетная модуляция сфинголипидного пути – ферментов сфингозинкиназы, церамидсинтаз, сфингомиелиназ и белка-переносчика церамидов, а также рецепторов S1P, может стать перспективным направлением сохранения овариального резерва, профилактики бесплодия и преодоления химиорезистентности при раке яичников. S1P демонстрирует защитные свойства в отношении ооцитов, а аналоги церамидов и ингибиторы сфинголипидных ферментов открывают новые возможности персонализированной терапии. Обобщение современных данных о сфинголипидном обмене в репродуктивных тканях позволяет рассматривать эти молекулы не только как маркеры патологии, но и как потенциальные терапевтические мишени, что особенно актуально для разработки стратегий сохранения фертильности и улучшения исходов лечения гинекологических заболеваний.

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