Xenotransplantation of pre-pubertal ovarian cortex and prevention of follicle depletion with anti-Müllerian hormone (AMH)

Abstract

Administration of recombinant AMH in the peri-transplant period did not protect the initial follicular depletion but decreased apoptosis and cellular activation and regulated stem cell markers' tissue expression. These results aid our understanding of the inhibitory effects of AMH on follicular development and show the benefit of administering exogenous AMH at the time of pre-pubertal ovarian cortex transplant to protect the follicles from pre-activation and premature depletion.

Long-Term Advantages of Ovarian Reserve Maintenance and Follicle Development Using Adipose Tissue-Derived Stem Cells in Ovarian Tissue Transplantation

“…AMH and estradiol concentrations were quantified in murine plasma every month, and the kinetic curves were constructed for each (Figure 2). High levels of detection of both hormones during surgery for xenotransplantation and ovariectomy (time point (TP) 0) were due to murine AMH and estradiol cross-reactivity, as demonstrated in other studies [20]. AMH values decreased after one month, as murine AMH was progressively washed out, then remained detectable at low levels until month 4, before increasing again 5 months post-transplantation (TP4 vs. TP5: p < 0.05; TP4 vs. TP6 p < 0.05).…”

“…AMH exerts its effect through AMHRII, mainly responsible for the phosphorylation of signaling pathway effectors of the Smad family [ 38 ]. AMHRII expression appears to decrease when AMH levels increase, suggesting negative feedback, as demonstrated in vivo using recombinant AMH [ 20 ].…”

Ovarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes

“…Both studies on AMH demonstrated an effect of its paracrine function on the follicle pool, but there was no evidence of any significant proangiogenic activity, as proved by absence of increased VEGF gene expression in Detti et al's study (Detti et al, 2018).…”

“…This approach, where AMH was released locally in the lumen of newly created vessels, showed increased retention of primordial follicles two weeks after OTT. Pump-mediated intraperitoneal infusion of recombinant AMH also had a protective effect on follicle outcomes 7 days after grafting, not by reducing follicle loss, but by mitigating abnormal follicle activation and growth (Detti et al, 2018).…”

“…Indeed, revascularization of ovarian tissue occurs progressively over days and does not correspond to the mechanisms of reperfusion, as in organ transplantation using vascular pedicles. Here, it occurs through neoangiogenesis, whereby mechanisms of sprouting angiogenesis from existing vessels (Macchiarelli et The whole process is modulated by oxygen tension which, through HIF1 signaling activation, induces proangiogenic growth factor secretion (26)(27)(28)(29). Responsible for endothelial cell proliferation and migration, VEGF appears to be increased 40-60-fold in grafted ovarian tissue soon after OTT) (Dissen et al, 1994;Yang et al, 2008).…”