Oxidative Stress in Granulosa-Lutein Cells From In Vitro Fertilization Patients

Abstract

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.

Symposium review: Mechanisms of disruption of fertility by infectious diseases of the reproductive tract

“…Apart from direct damage inflicted on oocytes by oxidative stress, granulosa cell function may be impaired, adding indirectly to functional impairment of associated oocytes. Evidence of oxidative stress in granulosa cells recovered along with oocytes for human in vitro fertilization was more severe for oocytes that failed to become fertilized or develop to blastocyst stage (Ávila et al, 2016;Lai et al, 2018), indicating that oxidative stress, at least at the antral stage of follicular development, has a detrimental effect on the follicle and oocyte.…”

Antioxidative enzyme-related gene expression levels in cumulus cells during in vitro fertilization: A comparison between normal and poor ovarian responders

“…According to the IVF outcomes, none of the genes in our study were correlated with fertilization or pregnancy rates. Although various evidences indicated the correlation between oxidative stress and IVF outcomes [26], the gradual decrease of antioxidant activity in advanced-age related cohorts, both POR and NOR participants, as presented in our study should be considered. Indisputably, oocyte quantity and quality have tremendously declined in advanced-age patients [27].…”

Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women

“…This coincides well with the increase of SIRT1 expression in response to age dependent OS. A direct correlation between aging and OS increase has been reported with aging-related decay of fertility [59], and our laboratory reported an increased expression levels of the oxidative stress response gene ALDH3A2 in granulosa-lutein cells that is related to age and infertility diagnosis [60,61].…”