Immunonutrients involved in the regulation of the inflammatory and oxidative processes: implication for gamete competence

Laura Di Renzo, Antonino De Lorenzo, Marco Fontanari, Paola Gualtieri, Diego Monsignore, Giulia Schifano, Valentina Alfano, Marco Marchetti, SIERR, Laura Di Renzo, Antonino De Lorenzo, Marco Fontanari, Paola Gualtieri, Diego Monsignore, Giulia Schifano, Valentina Alfano, Marco Marchetti, SIERR

Abstract

Purpose: The purpose of this umbrella review is to bring together the most recent reviews concerning the role of immunonutrients for male and female infertility.

Methods: Regarding immunonutrients and fertility, the authors have analyzed reviews, systematic reviews, and meta-analyses published between 2011 and June 2021. All reviews on animal or in vitro studies were excluded. Relevant keywords to term micronutrients were analyzed alone or in association with other terms such as "gamete competence," "male OR female fertility," "male OR female infertility," "fertile, "folliculogenesis," "spermatogenesis," "immunomodulation," "immune system," "oxidative stress."

Results: The primary research has included 108 results, and after screening by title, abstract. and not topic-related, 41 studies have been included by full texts. The results show the molecular mechanisms and the immunonutrients related impact on gamete formation, development. and competence. In particular, this review focused on arginine, glutamine, vitamin C, vitamin D, vitamin E, omega-3, selenium, and zinc.

Conclusions: Inflammation and oxidative stress significantly impact human reproduction. For this reason, immunonutrients may play an important role in the treatment of infertile patients. However, due to the lack of consistent clinical trials, their application is limited. Therefore, the development of clinical trials is necessary to define the correct supplementation, in case of deficiency.

Keywords: Antioxidant system; Gamete competence; Immunonutrients; Infertility; Inflammation; Oxidative stress; Supplementation.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of selection of reviews, systematic reviews, and metanalysis published
Fig. 2
Fig. 2
Main signaling pathways in male and female gametes. Omega-3 (ω-3) fatty acids (EPA, DHA) can promote the heterodimer peroxisome proliferator-activated receptor-γ/retinoid X receptor (PPAR-γ/RXR) activation and migration through the nuclear membrane to enhance DNA transcription, blocking Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) related inflammation processes. Vitamin D (VD) can lead RXR related DNA transcription via vitamin D responsive elements (VDREs) binding, essential for correct spermatogenesis and oocytes formation/development. In addition, VD can increase intracellular calcium (Ca2+) necessary for spermatozoa motility or oocytes maturation. Selenium (Se), as an essential cofactor for Glutathione peroxidase (GPx) enzymes and vitamin E, can lock reactive oxygen species (ROS) storm from lipid peroxidation. Zinc (Zn) binding to superoxide dismutase 2 (SOD2) can block intracellular ROS production, assisted by L-Arginine activity through inhibition of nitric oxide (NO) production. Activation of mammalian target of rapamycin (mTOR) by L-glutamine can inhibit autophagy and promote protein synthesis

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