Mesenchymal Stem Cell-Conditioned Medium Modulates Apoptotic and Stress-Related Gene Expression, Ameliorates Maturation and Allows for the Development of Immature Human Oocytes after Artificial Activation

Abstract

The aim of the present study was to determine whether mesenchymal stem cell-conditioned medium (MSC-CM) modulates apoptotic and stress-related gene expression, and ameliorates maturation and developmental potential of immature human oocytes after artificial activation. A total of 247 surplus immature germinal vesicle (GV) oocytes obtained from infertile women were allocated into two in vitro maturation (IVM) groups: 1: GV oocytes (n = 116) matured in vitro (fIVM), and 2: GV oocytes (n = 131) that were vitrified, then in vitro matured (vIVM). Also, two maturation media were used: Alpha-minimum essential medium (α-MEM) and human umbilical cord-derived MSCs (hUCM). After 36 h of incubation, the IVM oocytes were examined for nuclear maturation. In IVM-matured oocytes, cytoplasmic maturation was evaluated after artificial activation through Ionomycin. Moreover, the quantitative expressions of B-cell CLL/lymphoma 2 (BCL2), BCL2-associated X protein (BAX), superoxide dismutase (SOD), and Heat shock proteins (HSP70) in matured oocytes were assessed by quantitative Real-time polymerase chain reaction (qRT-PCR) and compared with fresh and vitrified in vivo matured oocytes, which were used as fIVM and vIVM controls, respectively. The highest maturation rate was found in hUCM in fIVM, and the lowest maturation rate was found using α-MEM in vIVM (85.18% and 71.42%, respectively). The cleavage rate in fIVM was higher than that in vIVM (83.4% vs. 72.0%). In addition, the cleavage rate in α-MEM was lower than that in the hUCM (66.0% vs. 89.4%). Furthermore, the difference between parthenote embryo arrested in 4–8 cells (p < 0.04) and the quality of embryo arrested in 8-cell (p < 0.007) were significant. The developmental stages of parthenote embryos in hUCM versus α-MEM were as follows: 2–4 cell (89.45% vs. 66.00%, respectively), 4–8 cell (44.31% vs. 29.11%, respectively), morula (12.27% vs. 2.63%, respectively), and blastocysts (2.5% vs. 0%, respectively). The messenger RNA (mRNA) expression levels of BCL2, BAX and SOD were significantly different (p < 0.05) between the matured IVM oocytes. Overall, hUCM showed potential efficacy in terms of ameliorating oocyte maturation and in promoting the development and mRNA expression of BAX, BCL2, and SOD.

Human Adipose-Derived Stem Cells’ Paracrine Factors in Conditioned Medium Can Enhance Porcine Oocyte Maturation and Subsequent Embryo Development

“…Additionally, they proved the conditioned media have a promising ability to improve IVM of polycystic ovary syndrome oocytes. In addition, human umbilical cord stem cells derived conditioned medium showed potential efficacy in terms of improving oocyte maturation and mRNA expression related to apoptosis [ 27 ].…”

Investigation of Stem Cell Applications on In Vitro Fertilization in Rats

“…The parthenogenesis induced with ionomycin was enhanced in the presence of CM in comparison with AMM. In the AMM, there was no seen the develeopment of blastocyst, whereas 5% blastocyst development was reported in the CM in the non-vitrified oocytes (Akbari et al, 2017). In another clinical study, the effects of CM of ADSCs on sperm motility and viability were searched.…”

“…Because, the MSCs secreted the cytokines and growth factors into the CM, and it is thought taht the CM will have an improvement effect on the reproductive cells and organs (Ullah et a., 2015;de Olivera Bezerra et al, 2019;Yang et al, 2019). Bader et al, reported that the CM of ADSCs rised the sperm motility in vitro condition, whereas Akbari et al, appointed that CM of human umblical cord mesenchymal stem cells prometed the oocyte maturation and the formation of blastocyst (Akbari et al, 2017;Bader et al, 2018).…”

Therapeutic Potential of HUMSCs in Female Reproductive Aging

“…developmental potential of artificially activated the maturation and developmental potential of immature human oocytes after the activation (Akbari et al, 2017). Thus suggesting that perhaps conditioned medium from HUMSCs in vitro, induced by the same factors in vivo, could also be therapeutic for the disease.…”

“…Compared with normal medium, HUMSCs-CM protected both frozen and thawed ovarian tissues ( Jia et al, 2017 ), and in a model of cisplatin-induced ovarian injury, HUMSCs-CM alleviated cisplatin-induced follicular failure and maintained fertility ( Hong et al, 2020 ), and in follicular development, HUMSCs-CM improved the maturation and developmental potential of artificially activated the maturation and developmental potential of immature human oocytes after the activation ( Akbari et al, 2017 ). Thus suggesting that perhaps conditioned medium from HUMSCs in vitro , induced by the same factors in vivo , could also be therapeutic for the disease.…”