A New Bioreactor to Promote Human Follicular Growth with or without Activin A in Transgender Men

Abstract

The aim of the present study was to evaluate the effect of activin A on the activation of in vitro folliculogenesis of human ovarian tissues from transgender men with or without our new compartmented chitosan hydrogel microbioreactor (“three-dimensional (3D)-structure”) enabling a three-dimensional tissue culture. Five fresh ovarian human tissues were cultured in vitro for 20 or 22 days in four groups with 100 ng/mL activin A or without activin A during the last six to eight days of culture, and within a 3D-structure or without the 3D-structure in standard conditions. Follicular density and quality were evaluated, and follicular diameters were measured. Estradiol secretion was quantified. Proliferation and apoptosis through immunostaining were also performed. The proportion of primordial follicles was significantly reduced, and the proportion of primary and secondary follicles was significantly increased in all four groups (p < 0.001). Tertiary follicles were observed in the four culture groups. Activin A supplementation did not significantly affect the follicular density, follicular quality, follicular growth, or estradiol secretion (p > 0.05). The 3D-structure increased the density of primary follicles and decreased the estradiol secretion (p < 0.001). Follicular proliferation was significantly lower in the 3D-structure group compared to the non-3D-structure group (p = 0.008). Regarding follicular apoptosis, it was significantly higher in the activin group compared to the non-activin group (p = 0.006). Activin A did not seem to play a key role in the in vitro folliculogenesis activation in our culture conditions. However, the results may indicate that the 3D-structure could be more physiological and could prevent a detrimental in vitro folliculogenesis flare-up.

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“…Proliferation and apoptosis were also assessed. Spontaneous folliculogenesis was observed regardless of the presence of the 3D structure or activin A [20]. The final data demonstrated that activin A did not play a crucial role in the in vitro folliculogenesis and supported the efficacy of the use of the 3D structure to induce a more physiological folliculogenesis, and to prevent its deleterious, excessive and hasty activation [20].…”

“…In proper culture systems, the addition of activin A, a dimeric glycoprotein belonging to the transforming growth factor beta superfamily that acts on a specific receptor expressed in primordial, primary, and secondary follicles, seemed to activate the primordial follicles and to initiate follicle growth [16][17][18][19]. An experimental study by Jovet et al [20] evaluated the efficacy of a new compartmented chitosan hydrogel microbioreactor ["three-dimensional (3D)-structure"] to activate the in vitro folliculogenesis of human ovarian fragments from transgender men, with or without activin A. Five fresh ovarian human tissues were cultured in vitro, and the follicular morphology, density and quality were evaluated, as well as estradiol production.…”