Exploring the innovative application of cerium oxide nanoparticles for addressing oxidative stress in ovarian tissue regeneration

Abstract

The female reproductive system dysfunction considerably affects the overall health of women and children on a global scale. Over the decade, the incidence of reproductive disorders has become a significant source of suffering for women. Infertility in women may be caused by a range of acquired and congenital abnormalities. Ovaries play a central role in the female reproductive function. Any defect in the normal functioning of these endocrine organs causes health issues and reproductive challenges extending beyond infertility, as the hormones interact with other tissues and biological processes in the body. The complex pathophysiology of ovarian disorders makes it a multifactorial disease. The key etiological factors associated with the diseases include genetic factors, hormonal imbalance, environmental and lifestyle factors, inflammatory conditions, oxidative stress, autoimmune diseases, metabolic factors, and age. Oxidative stress is a major contributor to disease development and progression affecting the oocyte quality, fertilization, embryo development, and implantation. The choice of treatment for ovarian disorders varies among individuals and has associated complications. Reproductive tissue engineering holds great promise for overcoming the challenges associated with the current therapeutic approach to tissue regeneration. Furthermore, incorporating nanotechnology into tissue engineering could offer an efficient treatment strategy. This review provides an overview of incorporating antioxidant nanomaterials for engineering ovarian tissue to address the disease recurrence and associated pathophysiology. Cerium oxide nanoparticles (CeO₂ NPs) are prioritized for evaluation primarily due to their antioxidant properties. In conclusion, the review explores the potential applications of CeO₂ NPs for effective and clinically significant ovarian tissue regeneration.

Keywords: Cerium oxide nanoparticles; Female infertility; Nanotechnology; Ovarian tissue engineering; Oxidative stress.

Fig. 1

Anatomy of ovary and follicle

Fig. 2

Prominent ovarian diseases

Fig. 3

Role of ROS in disease pathophysiology

Fig. 4

Enzyme mimetic action of nanoceria

Fig. 5

Application of cerium oxide nanoparticles for improving reproductive health. 1A. Morphology of tumor induced mouse untreated and treated with nanoceria. 1B. Representative H&E staining of treated and untreated xenografts with necrotic (pink) and live (purple) areas. (ii) Representative Ki-67 staining of xenografts [171] 2A. Image of endometrial tissue H&E staining of endometriotic mice injected with (A) 0.9% NaCl (B) NAC (C) Nanoceria (D) control healthy mice with 0.9% NaCl. The arrow indicated endometrial glands. 2B. Peritoneal cavity of endometriotic mice with similar treatment method and arrow indicates visible blood vessels [169] 3A. Ovarian sections H&E images of mice fed with ND, HFD, HFD + CeO2 NPs at 0.1 mg/kg and 0.5 mg/kg. Enlarged images show the primordial follicles of each group. 3B. Representative images of 2-cell and blastocyst embryos from each group [178] 4A. Transmission electron microscopy images of follicles and oocytes exposed to CeO2 NPs. Arrow indicating their accumulation [172] 5A. Representative image showing mitochondrial distribution in control, 24 h POA, LA-PEG-CeNPs stained using Mito Tracker Green. 5B. The images of spindle morphology stained with Tubulin tracker green and chromosome alignment with Hoechst in each group. 5C. Representative images to assess the fertilization and embryonic development showing the 2 cells and blastocyst developed from each group [180] 6A. Light microscopy images of in vitro matured oocytes of nanoceria treated mice at M-I stage after 4 h culture and M-II stage after 20 h culture. 6B. Fluorescent microscopy image of Hoechst 33,342 and propidium iodide-stained follicular cells: 1-viable cells, 2-apoptotic cells, 3-necrotic cells, 4-apoptotic bodies [170]