Ovarian Grafts 10 Days after Xenotransplantation: Folliculogenesis and Recovery of Viable Oocytes

Abstract

Ovarian xenotransplantation is a promising alternative to preserve fertility of oncologic patients. However, several functional aspects of this procedure remained to be addressed. The aim of this study was evaluate the feasibility of xenotransplantation as a strategy to maintain bovine ovarian grafts and produce oocytes. Adult ovarian cortical pieces were xenotransplanted to the dorsal subcutaneous of female NOD-SCID mice (n = 62). Grafts were recovered ten days after xenotransplantation. Host and graft weights; folliculogenesis progression; blood perfusion, relative gene expression and number of macrophage and neutrophil of xenografts; in vitro developmental competence of graft-derived oocytes were evaluated. Folliculogenesis was supported in the grafts, as indicated by the presence of primordial, primary, secondary, antral, and atretic follicles. The xenografts showed a greater volumetric density of atretic follicles and higher hyperemia and number of host-derived macrophage and neutrophil (P<0.05), when compared to non-grafted fragments. There was a higher blood perfusion under the back skin in the transplantation sites of host animals than in control and non-grafted (P<0.01). BAX and PRDX1 genes were up-regulated, while BCL2, FSHR, IGF1R and IGF2R were down-regulated, when compared to the control (P<0.01). Twenty seven oocytes were successfully harvested from grafts, and some of these oocytes were able to give rise to blastocysts after in vitro fertilization. However, cleavage and blastocyst rates of xenograft derived oocytes were lower than in control (P<0.01). Despite showing some functional modifications, the ovarian xenografts were able to support folliculogenesis and produce functional oocytes.

Xenotransplantation of goat ovary as an alternative to analyse follicles after vitrification

“…However, only fresh and vitrified transplant showed detectable mRNA expression of BLC2 . In contrast to our study, Campos‐Junior et al () showed a significant increase in BAX and a decrease in BCL2 after xenotransplantation of the bovine ovary to mice. The increase in BCL2 in our study after xenotransplantation can be a cell response in an attempt to overcome the apoptosis process (Lunardi et al, ), showing that the living cells present in the tissue could resume their function.…”

Influence of graft size, histocompatibility,and cryopreservation on reproductive outcome following ovary transplantation in mice

“…Immunodeficient mice are frequently used as recipients for xenotransplantation [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Reports about transplantation of mouse ovaries into immunodeficient mice are rare.…”

“…Alternatively, adult immunodeficient mouse mutants could serve as universal recipients but are still rarely used for the transplantation of mouse ovaries [12,14]. In contrast, immunodeficient mice have frequently been used for xenotransplantation as recipients for ovary pieces from the rat [15], human [16][17][18][19][20][21], sheep [22,23], cat [24,25], cattle [26,27], wombat [28], elephant [29], dog [30,31], and lion [32].…”

The CC-chemokine receptor 2 is involved in the control of ovarian folliculogenesis and fertility lifespan in mice

“…Values are shown as n-fold difference. All procedures were performed as previously described by our group (Campos-Junior et al, 2016;Pereira et al, 2020).…”