Antioxidant Intervention Attenuates Aging-Related Changes in the Murine Ovary and Oocyte

Abstract

Advanced maternal age (AMA) is associated with reduced fertility due in part to diminished ovarian follicle quantity, inferior oocyte quality, chromosome aneuploidy, and lower implantation rates. Ovarian aging is accompanied by increased oxidative stress and blunted antioxidant signaling, such that antioxidant intervention could improve reproductive potential. The first aim of this study was to determine the molecular effects of antioxidant intervention in the ovaries and oocytes of aged mice, utilizing a supplement containing only naturally occurring açaí (Euterpe oleracea) with an oxygen radical absorbance capacity of 208,628 μmol Trolox equivalent (TE)/100 g indicating high antioxidant activity. Nine month old female CF-1 mice were administered 80 mg/day antioxidants (n = 12) or standard diet (n = 12) for 12 weeks. In the ovary, antioxidant treatment upregulated β-adrenergic signaling, downregulated apoptosis and proinflammatory signaling, and variably affected cell growth and antioxidant pathways (p < 0.05). Exogenous antioxidants also increased the oocyte expression of antioxidant genes GPX1, SOD2, and GSR (p < 0.05). A feasibility analysis was then conducted on female AMA infertility patients as a proof-of-principle investigation. Patients (n = 121; <45 years old) consented to receiving 600 mg antioxidants three times daily for ≥8 weeks preceding infertility treatment. Preliminary results indicate promising outcomes for AMA patients, warranting further investigation.

Increased Systemic Antioxidant Power Ameliorates the Aging-Related Reduction in Oocyte Competence in Mice

“…Although the antioxidant treatment improved oocyte competence, it did not affect oocyte number. This is similar to what others have reported in animal models [ 29 ], and is what we expected based on our clinical observations [ 28 ]. Ovarian aging is associated with a loss of both the ovarian reserve and oocyte quality [ 2 ], and in this study we targeted the latter with a later-in-life antioxidant intervention.…”

“…Açaí intervention has been shown to reduce oxidative stress in animal models of high-fat diet-induced obesity, renovascular hypertension, and acute colitis, among others [ 25 , 26 , 27 ]. Our preliminary work investigating the açaí berry in mice revealed positive effects on ovarian and oocyte signaling, with upregulated antioxidant signaling and lower markers of ER stress and apoptosis [ 28 ]. Clinically, the use of this antioxidant supplement prior to egg retrieval resulted in a high live birth rate following single euploid frozen embryo transfer in patients with prior in vitro fertilization (IVF) failures [ 28 ].…”

Effects of Coenzyme Q10 on Ovarian Surface Epithelium-derived Ovarian Stem Cells and Ovarian Function in 4-vinylcyclohexene Diepoxide-induced Ovarian Failure Mice.

“…Due to these characteristics, OS induces senescence of the cells and diminishing ovarian reserves, follicular atresia, and poor oocyte quality in the ovary [3]. In this respect, antioxidants have been attempted as one of the key components to prevent OS-induced ovarian aging by improving mitochondrial function [4][5][6].…”

Special Issue “Reproductive Health Concerns for Women”

“…The current assisted reproductive technique (ART) involving oocyte retrieval and the subsequent in vitro fertilization, or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET), has been widely used for the therapy in a certain population of couples with infertility [9,10]. However, advanced maternal age (AMA) may be one of the biggest challenges during the ART due in part to diminished ovarian reservation, poor oocyte quality, chromosome aneuploid, and a lower implantation rate [11]. Based on the concept of the increased oxidative stress and blunted antioxidant signaling in aged ovary, Katz-Jaffe et al utilized a supplement containing a natural antioxidant agent to show how upregulated β-adrenergic signaling, downregulated apoptosis, and proinflammatory signaling variably affected cell growth and antioxidant pathways as well as the increased expression of antioxidant genes, such as GPX1, SOD2, and GSR in the aged oocyte [11].…”

“…However, advanced maternal age (AMA) may be one of the biggest challenges during the ART due in part to diminished ovarian reservation, poor oocyte quality, chromosome aneuploid, and a lower implantation rate [11]. Based on the concept of the increased oxidative stress and blunted antioxidant signaling in aged ovary, Katz-Jaffe et al utilized a supplement containing a natural antioxidant agent to show how upregulated β-adrenergic signaling, downregulated apoptosis, and proinflammatory signaling variably affected cell growth and antioxidant pathways as well as the increased expression of antioxidant genes, such as GPX1, SOD2, and GSR in the aged oocyte [11]. In clinical practice, using antioxidant supplements prior to the IVF cycle in women older than 39 also showed a promising result for AMA patients [11], suggesting an understanding of the ageing process of the ovary and that a strategy of using various kinds of agents to slow down the ageing process of the ovary may be possible, although there is still a long way to go [12,13].…”