Human mesenchymal stem cell treatment of premature ovarian failure: new challenges and opportunities

Abstract

Premature ovarian failure (POF) is one of the common disorders found in women leading to 1% female infertility. Clinical features of POF are hypoestrogenism or estrogen deficiency, increased gonadotropin level, and, most importantly, amenorrhea. With the development of regenerative medicine, human mesenchymal stem cell (hMSC) therapy brings new prospects for POF. This study aimed to describe the types of MSCs currently available for POF therapy, their biological characteristics, and their mechanism of action. It reviewed the latest findings on POF to provide the theoretical basis for further investigation and clinical therapy.

Domestication Explains Two-Thirds of Differential-Gene-Expression Variance between Domestic and Wild Animals; The Remaining One-Third Reflects Intraspecific and Interspecific Variation

“…Recently [ 57 , 58 ], an RNA-Seq data analysis was based on this oldest phylogeny concept [ 59 ] widely used elsewhere [ 60 , 61 , 62 , 63 ]. Let us look at these orthologous genes one by one and discuss effects of their expression changes on reproductive potential in humans as well as during divergence of domestic and wild animals from their most recent com-mon ancestor [ 24 , 25 , 28 , 29 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 ] ( Table 8 ).…”

“…Human gene NR5A1 encodes steroidogenic factor 1, both a deficit and excess of which reduce human reproductive potential on the one hand via hyper-anxiety during impaired aggressive sexual behavior up to male infertility [ 77 ] as well as hypoestrogenism [ 78 ] leading to 1% of cases of female infertility [ 79 ], and on the other hand, hyperestrogenism elevates risks of endometriosis and others estrogen-dependent inflammatory disorders in women [ 80 , 81 ]. That is why both domestic and wild forms of rats [ 82 ], chickens [ 29 ], rabbits [ 28 ], and guinea pigs [ 25 ] could have paid with their health (i.e., hormonal dysregulation) for the benefits that each of them got during microevolution ( Table 8 ).…”

“…within human disease models based on Nr5a1-null male mice: hyper-anxiety during impaired aggressive sexual behavior up to male infertility in line with male patients carrying NR5A1 defects [77] as well as NR5A1 deficit can cause hypoestrogenism [78] leading to 1% of cases of female infertility [79] → in retrospective meta-analysis of PubMed content: NR5A1 excess contributes to excessive estrogen biosynthesis raising risks of estrogen-dependent inflammatory disorders in women [80] Human gene SHOX (short stature homeobox) underexpression is an adaptive epigenetic response to adverse living conditions in humans according to a cohort-based study [83] because each calorie saved due to short stature helps to enhance stress resistance [84]. This SHOX insufficiency in humans corresponds to a Shox2 deficit [87] in aggressive rats under study.…”

Ovarian Decellularized Bioscaffolds Provide an Optimal Microenvironment for Cell Growth and Differentiation In Vitro

“…Radiotherapy, chemotherapy, viral infections, environmental factors, metabolic and autoimmune disorders, and genetic alterations represent some of the potential causes identified so far. The clinical features displayed by affected patients are hypoestrogenism or estrogen deficiency, increased gonadotropin levels, and amenorrhea [4]. POF also impacts the overall quality-of-life, since alterations in ovarian hormone levels are responsible for different side effects on other organs and tissues, which lead to both medical and psychological problems, such as osteoporosis, cardiovascular disease, and depression [5][6][7].…”

“…Indeed, to date, several options have been proposed to overcome this challenging issue, including cryopreservation and transplantation of oocytes, embryos, and autologous ovarian fragments, as well as hormone replacement therapies [8][9][10]. However, all of these strategies present limitations and are not fully effective in a complete recovery of the ovarian function [4]. The development of novel and efficient therapeutic alternatives is therefore urgently needed.…”