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Antioxidants combat high-fat diet-induced female reproductive issues, study reveals


In a systematic review published in the journal Frontiers in Nutrition, researchers in Italy have provided a comprehensive overview of the impact of biological matrices with antioxidant properties in mitigating high-fat diet-induced female reproductive complications.

Review: High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices. Image Credit: DIVA.photo / ShutterstockReview: High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices. Image Credit: DIVA.photo / Shutterstock

Background 

High-calorie diets, including diets rich in saturated and trans fats, can negatively impact the female reproductive system by triggering the production of reactive oxygen species (ROS) and subsequently inducing oxidative stress. This can lead to irregular ovulation patterns and premature ovarian failure.

Diet-induced ROS production can affect blood flow to the reproductive organs and disrupt the functioning of the hypothalamic-pituitary-ovarian axis. These processes can collectively cause reproductive hormonal imbalance, induce insulin resistance and hyperleptinemia, promote chronic low-grade inflammation, affect oocyte quality, and impair uterine embryo implantation and pregnancy maintenance.

Biological matrices that can positively impact the female reproductive system include carbocyclic sugar, phytonutrients, organosulfur compounds, hormones, neuropeptides, organic acids, and vitamins. These matrices mostly contain a variety of antioxidants that help mitigate ROS-induced oxidative damage in the body.   

In this systematic review, the authors have assessed the effectiveness of biological matrices in preventing ovarian complications caused by high-fat diet-induced oxidative stress. They have analyzed 121 studies published in peer-reviewed English-language journals.

Antioxidants derived from biological matrices and their impact on high-fat diet-induced oxidative stress

Folliculogenesis refers to the maturation of primordial germ cells into oocytes within follicles, which is a vital process for optimal female reproductive functioning.

A high-fat diet can cause oxidative damage to the ovaries by specifically targeting follicle development, survival, and the production of hormones essential for folliculogenesis regulation. These factors can subsequently affect oocyte quality and compromise embryo development.

In rodent models of high-fat diet-induced oxidative stress, a diet containing a combination of two phytonutrients, barley, and dates, has been found to preserve ovarian follicles, increase follicle development and proliferation, restore ovarian stroma, and increase endogenous enzymatic antioxidant levels.

These positive outcomes can be attributed to increased activities of flavonoids and phenolic-antioxidant properties found in Okra, ferulic acid, kaempferol, malvidin, caffeoylquinic acid, and quercetin derivatives.

In mouse models of high-fat diet-induced oxidative stress, a thymoquinone-containing diet has been found to activate the AMPK/PGC1α/SIRT1 pathway, increasing antioxidant status, reducing inflammation, and improving mitochondrial functions. These changes are associated with an induction in the number of early-stage follicles and an improvement in oocyte quality.

A diet containing neuropeptide phoenixin has been found to reduce ovarian weights, decrease peri-ovarian fat pads, modulate luteinizing hormone (LH) receptor positivity in rodents, and reduce apoptosis and inflammation in the ovaries of rodents exposed to a high-fat diet.

In obese rats, a multi-antioxidant supplement, including organosulfur compound, phytonutrients, vitamin E, and Coenzyme Q10, has been found to reduce ovarian inflammation and follicular atresia and mitigate obesity-induced infertility.

In rats exposed to a high-fat diet, a diet containing apple vinegar and phoenixin has been found to rectify hormonal imbalance, increase folliculogenesis, and improve antioxidant response in the ovaries.

A diet containing ferulic acid, kaempferol, malvidin, caffeoylquinic acid, and quercetin derivatives has been found to increase both enzymatic and non-enzymatic antioxidants in rats exposed to a high-fat diet, leading to the protection of oocytes against DNA damage.

Similarly, MitoQ10 supplementation has been found to reduce high-fat diet-induced oxidative stress and improve mitochondrial functions, mitigating DNA damage and preserving oocyte quality.

Organosulfur compounds have been found to ameliorate infertility caused by high-fat diet-induced obesity. Dietary interventions containing ferulic acid, kaempferol, malvidin, caffeoylquinic acid, and quercetin derivatives, as well as the combined use of myo-inositol and α-lipoic acid, have been found to protect against ovarian cycle disruption and reduce ovarian degenerative changes caused by high-fat diet-induced oxidative stress.

Overall, existing literature indicates that biological matrices as antioxidants can effectively reduce the number of atretic follicles, ovarian inflammation, and ovarian apoptosis. This is evidenced by decreased ovarian weights, reduced peri-ovarian fat pads, and modulated LH receptor positivity.

Biological matrices-derived antioxidants as dietary components: their influence on ovarian health and modulation of the complex interplay between high-fat diet-induced oxidative stress and reproductive function. Adipose tissue derived from a high-fat diet regimen can precipitate the production of reactive oxygen species (ROS) and subsequent oxidative stress through multifaceted pathways. Notably, the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase prompts ROS generation, fostering the upregulation of adipocytokines and cytokines, thus inciting inflammation and facilitating macrophage infiltration into adipose tissue. Furthermore, the heightened levels of ROS induce dysfunction within mitochondrial complex II, disrupting the electron transport chain and exacerbating ROS production. This intricate interplay underscores the pivotal role of oxidative stress in the pathophysiology of adipose tissue dysfunction amidst high-fat dietary habits. Connecting this phenomenon to fatty acid metabolism elucidates a complementary narrative, where electron transfer along the electron transport chain generates ROS as byproducts. Specifically, fatty acid metabolism within mitochondria serves as a prime site for ROS generation, with various complexes along the electron transport chain serving as key contributors. Consequently, the accrual of ROS can overwhelm endogenous antioxidant defenses, precipitating oxidative stress and consequent cellular damage. Such insights underscore the significance of biological matrices endowed with antioxidant properties, as they offer promising avenues for ameliorating the adverse effects of oxidative stress on physiological processes, including reproductive health. SOD, superoxide dismutase; GPx, glutathione peroxidase; GSSG, glutathione oxidase; GSH, glutathione reductase; ROS, reactive oxygen species; O2-•, superoxide; H2O2, hydrogen peroxide; OH•, Hydroxyl. Image created with Biorender.com.

Biological matrices-derived antioxidants as dietary components: their influence on ovarian health and modulation of the complex interplay between high-fat diet-induced oxidative stress and reproductive function. Adipose tissue derived from a high-fat diet regimen can precipitate the production of reactive oxygen species (ROS) and subsequent oxidative stress through multifaceted pathways. Notably, the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase prompts ROS generation, fostering the upregulation of adipocytokines and cytokines, thus inciting inflammation and facilitating macrophage infiltration into adipose tissue. Furthermore, the heightened levels of ROS induce dysfunction within mitochondrial complex II, disrupting the electron transport chain and exacerbating ROS production. This intricate interplay underscores the pivotal role of oxidative stress in the pathophysiology of adipose tissue dysfunction amidst high-fat dietary habits. Connecting this phenomenon to fatty acid metabolism elucidates a complementary narrative, where electron transfer along the electron transport chain generates ROS as byproducts. Specifically, fatty acid metabolism within mitochondria serves as a prime site for ROS generation, with various complexes along the electron transport chain serving as key contributors. Consequently, the accrual of ROS can overwhelm endogenous antioxidant defenses, precipitating oxidative stress and consequent cellular damage. Such insights underscore the significance of biological matrices endowed with antioxidant properties, as they offer promising avenues for ameliorating the adverse effects of oxidative stress on physiological processes, including reproductive health. SOD, superoxide dismutase; GPx, glutathione peroxidase; GSSG, glutathione oxidase; GSH, glutathione reductase; ROS, reactive oxygen species; O2-•, superoxide; H2O2, hydrogen peroxide; OH•, Hydroxyl. Image created with Biorender.com.

Clinical relevance of biological matrices as antioxidants

Assisted reproductive technology is considered a conventional infertility treatment. However, this treatment cannot effectively target underlying infertility causes related to a high-fat diet. Biological matrices as antioxidants have shown promising outcomes in treating these issues.

Omega-3 fatty acids and vitamin B12 have been found to reduce the symptoms of endometriosis, a hormone-related, chronic inflammatory condition affecting women of childbearing age.

Randomized controlled clinical trial findings highlight the efficacy of vitamins E and C in reducing pelvic pain and peritoneal fluid inflammatory markers.

Biological matrices comprising vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin C, vitamin D3, vitamin E, nicotinamide, and folic acid have been found to improve pregnancy rates in women with polycystic ovary syndrome (PCOS).

Resveratrol treatment of PCOS patients has been found to improve the quality of oocytes and embryos. Similarly, treatments with vitamins D and E have been found to increase the rates of implantation and overall pregnancy success, respectively.



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