Magdalena Pertynska-Marczewska1, Evanthia Diamanti-Kandarakis. 1. 1Independent Consultant in Obstetrics and Gynecology, New Malden, UK 2Department of Endocrinology and Diabetes Center of Excellence, Medical School of Athens, Athens, Greece.
Abstract
OBJECTIVE: The hypothalamic gonadotropin-releasing hormone pulse generator, the pituitary gonadotropes, the ovaries, and the uterus play a crucial role in female fertility. A decline in reproductive performance represents a complex interplay of actions at all levels of the hypothalamic-pituitary-ovarian axis. Recently, in the field of female reproductive aging attention is drawn to the carbonyl stress theory. Advanced glycation end products (AGEs) contribute directly to protein damage, induce a chain of oxidative stress (OS) reactions, and increase inflammatory reactions. Here, we highlight some of the mechanisms underlying glycation damage in the ovary. METHODS: Searches of electronic databases were performed. Articles relevant to possible role of OS, AGEs, and receptor for AGE (RAGE) in aging ovary were summarized in this interpretive literature review. RESULTS: Follicular microenvironment undergoes an increase in OS with aging. Data support the role of OS in ovulatory dysfunction because AGEs are well-recognized mediators of increased OS. RAGE and AGE-modified proteins with activated nuclear factor-kappa B are expressed in human ovarian tissue. It was suggested that accumulation of AGEs products at the level of the ovarian follicle might trigger early ovarian aging or could be responsible for reduced glucose uptake by granulosa cells, potentially altering follicular growth. Moreover, impaired methylglyoxal detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive aging. CONCLUSIONS: Further investigation of the role for the AGE-RAGE axis in the ovarian follicular environment is needed, and results could relate to assisted reproduction technology outcomes and new measures of ovarian reserve.
OBJECTIVE: The hypothalamic gonadotropin-releasing hormone pulse generator, the pituitary gonadotropes, the ovaries, and the uterus play a crucial role in female fertility. A decline in reproductive performance represents a complex interplay of actions at all levels of the hypothalamic-pituitary-ovarian axis. Recently, in the field of female reproductive aging attention is drawn to the carbonyl stress theory. Advanced glycation end products (AGEs) contribute directly to protein damage, induce a chain of oxidative stress (OS) reactions, and increase inflammatory reactions. Here, we highlight some of the mechanisms underlying glycation damage in the ovary. METHODS: Searches of electronic databases were performed. Articles relevant to possible role of OS, AGEs, and receptor for AGE (RAGE) in aging ovary were summarized in this interpretive literature review. RESULTS: Follicular microenvironment undergoes an increase in OS with aging. Data support the role of OS in ovulatory dysfunction because AGEs are well-recognized mediators of increased OS. RAGE and AGE-modified proteins with activated nuclear factor-kappa B are expressed in human ovarian tissue. It was suggested that accumulation of AGEs products at the level of the ovarian follicle might trigger early ovarian aging or could be responsible for reduced glucose uptake by granulosa cells, potentially altering follicular growth. Moreover, impaired methylglyoxal detoxification causing relevant damage to the ovarian proteome might be one of the mechanisms underlying reproductive aging. CONCLUSIONS: Further investigation of the role for the AGE-RAGE axis in the ovarian follicular environment is needed, and results could relate to assisted reproduction technology outcomes and new measures of ovarian reserve.
Authors: Yan Yi; Samar R El Khoudary; Jeanine M Buchanich; Rachel G Miller; Debra Rubinstein; Trevor J Orchard; Tina Costacou Journal: Menopause Date: 2021-04-05 Impact factor: 2.953