Application of Perinatal Derivatives in Ovarian Diseases

Abstract

Reproductive diseases could lead to infertility and have implications for overall health, most importantly due to psychological, medical and socio-economic consequences for individuals and society. Furthermore, economical losses also occur in animal husbandry. In both human and veterinary medicine, hormonal and surgical treatments, as well as assisted reproductive technologies are used to cure reproductive disorders, however they do not improve fertility. With ovarian disorders being the main reproductive pathology in human and bovine, over the past 2 decades research has approached regenerative medicine in animal model to restore normal function. Ovarian pathologies are characterized by granulosa cell and oocyte apoptosis, follicular atresia, decrease in oocyte quality and embryonic development potential, oxidative stress and mitochondrial abnormalities, ultimately leading to a decrease in fertility. At current, application of mesenchymal stromal cells or derivatives thereof represents a valid strategy for regenerative purposes. Considering their paracrine/autocrine mode of actions that are able to regenerate injured tissues, trophic support, preventing apoptosis and fibrosis, promoting angiogenesis, stimulating the function and differentiation of endogenous stem cells and even reducing the immune response, are all important players in their future therapeutic success. Nevertheless, obtaining mesenchymal stromal cells (MSC) from adult tissues requires invasive procedures and implicates decreased cell proliferation and a reduced differentiation capacity with age. Alternatively, the use of embryonic stem cells as source of cellular therapeutic encountered several ethical concerns, as well as the risk of teratoma formation. Therefore, several studies have recently focussed on perinatal derivatives (PnD) that can be collected non-invasively and, most importantly, display similar characteristics in terms of regenerating-inducing properties, immune-modulating properties and hypo-immunogenicity. This review will provide an overview of the current knowledge and future perspectives of PnD application in the treatment of ovarian hypofunction.

Guidelines to Analyze Preclinical Studies Using Perinatal Derivatives

“…From this extensive work of literature search and selection and data extraction, several systematic and comprehensive reviews are published already. These publications gathered and analyzed the existing literature on the application of preclinical studies on different fields, namely cutaneous wound healing [ 5 ], ovarian diseases [ 3 ], oncology [ 6 ], and ophthalmology [ 4 ]. All of these publications used the common search and data extraction strategy described here, with additional, disease-specific refinements as described in detail in the respective publications.…”

Protective role of stem cells in POI: Current status and mechanism of action, a review article

“…Oxidative stress is involved in several reproductive disorders including polycystic ovary syndrome (PCOS), endometriosis, and POI [ 22 ]. POI is also characterized by decreased antioxidant levels and increased oxidative stress in cumulus cells, oocytes and ovaries, and oxidative stress levels are correlated with worse outcomes [ 23 ]. Recently, gene set enrichment analysis (GSEA) using both Hallmark and KEGG gene sets in POI patients showed that POI is associated with inhibition of pathways related to oxidative phosphorylation, DNA damage repair and mitochondrial function, such as PI3K/AKT/mTOR pathways, and early and late estrogen response pathways [ 24 ].…”

Kurarinone attenuates hydrogen peroxide‐induced oxidative stress and apoptosis through activating the PI3K/Akt signaling by upregulating IGF1 expression in human ovarian granulosa cells

“…Lifestyle and environmental factors affect infertility, and great advances have gained on its diagnosis and management in recent years 2 . The ovarian disorders are the main reproductive pathologies contributing to infertility in female, including follicular atresia 3 . Granulosa cells are essential for follicular development, and dysfunctional granulosa cells are linked to follicular atresia progression 4,5 .…”

“…2 The ovarian disorders are the main reproductive pathologies contributing to infertility in female, including follicular atresia. 3 Granulosa cells are essential for follicular development, and dysfunctional granulosa cells are linked to follicular atresia progression. 4,5 The oxidative stress is one of the causal mediators of female reproductive diseases, 6 which leads to apoptosis of granulosa cells and subsequent follicular atresia.…”