Oxidative Stress in Granulosa-Lutein Cells From In Vitro Fertilization Patients.
Ovarian aging is associated with gradual follicular loss by atresia/apoptosis. Increased production of toxic metabolites such as reactive oxygen species (ROS) and reactive nitrogen species as well as external oxidant agents plays an important role in the process of ovarian senescence and in the pathogenesis of ovarian pathologies such as endometriosis and polycystic ovary syndrome (PCOS). This review provides a synthesis of available studies of oxidative stress (OS) in the ovary, focusing on the most recent evidence obtained in mural granulosa-lutein (GL) cells of in vitro fertilization patients. Synthesis of antioxidant enzymes such as peroxiredoxin 4, superoxide dismutase, and catalase and OS damage response proteins such as aldehyde dehydrogenase 3, member A2 decreases with aging in human GL cells, favoring an unbalance in ROS/antioxidants that mediates molecular damage and altered cellular function. The increase in OS in the granulosa cell correlates with diminished expression of follicle-stimulating hormone receptor (FSHR) and a dysregulation of the FSHR signaling pathway and may be implicated in disrupted steroidogenic function and poor response to FSH in women with aging. Women with endometriosis and PCOS have lower antioxidant production capacity that may contribute to abnormal follicular development and infertility. Further investigation of the signaling pathways involved in cellular response to OS could shed light into molecular characterization of these diseases and development of new treatment strategies to improve reproductive potential in these women.
Departamento de Bioquímica y Biología Molecular, Laboratorio de Biología del Desarrollo, Universidad de La Laguna, La Laguna, Spain.|Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Spain.
Julio
J
Ávila
Departamento de Bioquímica y Biología Molecular, Laboratorio de Biología del Desarrollo, Universidad de La Laguna, La Laguna, Spain.
Rebeca
R
González-Fernández
Departamento de Bioquímica y Biología Molecular, Laboratorio de Biología del Desarrollo, Universidad de La Laguna, La Laguna, Spain.|Institute of Endocrinology and Experimental Oncology (IEOS), CNR-National Research Council, Naples, Italy.
Deborah
D
Rotoli
Centro de Asistencia a la Reproducción Humana de Canarias, La Laguna, Spain.
Jairo
J
Hernández
Centro de Asistencia a la Reproducción Humana de Canarias, La Laguna, Spain apalumbo@fivap.com apalumbo1960@gmail.com.|Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
Angela
A
Palumbo
D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro; D006801:Humans; D008184:Luteal Cells / Q000378:metabolism*; D018384:Oxidative Stress; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011962:Receptors, FSH / Q000378:metabolism
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011962:Receptors, FSH
PCOS; ROS; endometriosis; granulosa cell; oxidative stress