Ovarian tissue culture in the presence of VEGF and fetuin stimulates follicle growth and steroidogenesis

Abstract

Ovarian tissue cryopreservation together with follicle culture provides a promising technique for fertility preservation in cancer patients. The study aimed to evaluate follicle parameters in a culture medium supplemented with VEGFA165 and/or fetuin. Vitrified-warmed ovarian cortical pieces were divided randomly into four culture groups consisting of basic culture medium (control), and the basic culture medium supplemented with VEGFA165, fetuin or both. After six days of culture, we evaluated the following: percentage of resting, primary and secondary growing follicles; survival rate; steroid hormones production; levels of reactive oxygen species, lipid peroxidation and total antioxidant capacity; and developmental and antioxidant gene expression. The addition of VEGFA165 alone or in combination with fetuin to the culture medium caused resting follicle activation and increased the number of growing follicles. In the VEGFA165 group, we found a significant increase in the concentrations of 17β-estradiol at day 6 and progesterone from 4th day of the culture period. In the VEGFA165 + fetuin group, the concentration of 17β-estradiol rose at day 4 of the culture period. The levels of BMP15, GDF9 and INHB mRNAs were increased in all treated groups. In the fetuin and fetuin + VEGFA165 groups, we observed a high level of total antioxidant capacity and expression of SOD1 and CAT genes, low reactive oxygen species and lipid peroxidation levels and increased number of viable follicles. In conclusion, the present study provides useful evidence that supplementation of culture medium with VEGFA165 + fetuin leads to primordial follicle activation and development and increased percentage of healthy secondary growing follicles.

Fetuin-A exerts a protective effect against experimentally induced intestinal ischemia/reperfusion by suppressing autophagic cell death

“…30 Additionally, we found that fetuin-A downregulated tissue MDA, TNF-a, and IL-1b levels. Furthermore, our results were in line with those of Asadi et al 31 who noticed that fetuin enhanced total antioxidant capacity levels and also prevented the formation of MDA in ovarian tissue. These findings are in agreement with the observations of Sarı€ ozkan et al, 32 who indicated that supplementation of the medium used to freeze sperm with fetuin or a combination of fetuin and hyaluronan decreased ROS and MDA levels.…”

Human Follicle in vitro Culture Including Activation, Growth, and Maturation: A Review of Research Progress

“…The increase of mRNA levels in cumulus cells is related to the oocyte maturity and fertilization rate ( 45 ), and the addition of GDF-9 or BMP-15 in IVC system can promote the activation of human primordial follicles, with seemingly more beneficial effects of GDF9 ( 46 ). Other factors, such as basic fibroblast growth factor (bFGF), kit ligand (KITL), keratinocyte growth factor (KGF), leukemia inhibitory factor (LIF), stem cell factor (SCF), vascular endothelial growth factor (VEGF), and cyclic adenosine monophosphate (cAMP), have also been proved to improve the activation and survival of cultured follicles in vitro ( 47 – 49 ). Shown in Table 1 .…”

Female fertility preservation: past, present and future

“…Various growth factors have been shown to promote some activation of primordial follicles in humans (Abir et al 2006, Garor et al 2009, Kedem et al 2011b, Streiter et al 2016 including stem cell factor (Carlsson et al 2006a), insulin and insulin-like growth factors (Yuan & Giudice 1999, Louhio et al 2000, Stubbs et al 2013, basic fibroblast growth factor (Garor et al 2009, Wang et al 2014, growth and differentiating factor 9 (Hreinsson et al 2002, Kedem et al 2011b, bone morphogenetic factor 15 (Kedem et al 2011b) and VEGF165 with fetuin (Asadi et al 2017). However, development was limited to early secondary stages.…”