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.
Highlights
INTRODUCTIONReproductive disorders are caused by different factors, including social, genetic, endocrine, physiological, psychological and lifestyle habits (e.g., smoking and alcohol consumption), and may lead to infertility (Agarwal et al, 2021; Farsimadan et al, 2021)
Reproductive disorders are caused by different factors, including social, genetic, endocrine, physiological, psychological and lifestyle habits, and may lead to infertility (Agarwal et al, 2021; Farsimadan et al, 2021)
Recent studies have shown that amniotic mesenchymal cells (AMSC) transplantation in rats with chemotherapy-induced premature ovarian insufficiency” (POI) restored ovarian function, grafted cells were only detectable in the interstitium of the ovaries and not in the follicles. These cells did not express the typical oocyte and granulosa cell markers, which are zona pellucida sperm-binding protein 3 (ZP3) and FSHR, respectively. These results suggest that grafted AMSC do not differentiate into oocytes or granulosa cells but are able to improve ovarian function via a paracrine mechanism (Ling et al, 2019)
Summary
Reproductive disorders are caused by different factors, including social, genetic, endocrine, physiological, psychological and lifestyle habits (e.g., smoking and alcohol consumption), and may lead to infertility (Agarwal et al, 2021; Farsimadan et al, 2021). Treated animal models displayed paralleled manifestations to clinic features of human POI patients, mainly oxidative stress and apoptosis of granulosa cells, with the consequence of a significant decrease of the number of follicles, level of hormones, weight of ovaries, and number of offspring, as reported in all papers used in this review. Several studies in rat and mouse models with induced POI have reported an increase of ROS levels that reduces oocyte quality due to granulosa cell apoptosis (Seok et al, 2020), which can cause a decrease in the number of follicles and a reduced level of oestrogen (Li et al, 2019) and AMH (Zhang H et al, 2018). MSC derived from bone marrow and adipose tissue displayed positive effects on damaged ovarian tissue in a POF mouse model, thereby promoting an increase in E2 level, suppressing apoptosis and promoting angiogenesis (Kim et al, 2018). Given this knowledge, exploring the use of PnD as a potential innovative therapy in ovarian diseases is highly encouraged
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