In vitro production (IVP) of bovine embryos frequently results in varying blastocyst yields, partly because culture conditions fail to support optimal oocyte and embryo development. In vivo, cumulus-oocyte complexes (COCs) mature under hypoxic conditions, and while in vitro protocols try to mimic the natural conditions, standard in vitro maturation (IVM) is typically performed under normoxia, guided largely by empirical outcomes rather than a biological understanding. We hypothesized that IVP efficiency would be improved by stabilization of hypoxia-inducible factor 1-alpha (HIF1A), via pharmacological inhibition of prolyl hydroxylase domain (PHD) activity, during IVM. To test this, we treated COCs with varying concentrations of Roxadustat, a PHD inhibitor. Low-dose treatment (25 µM) stabilized and significantly enhanced blastocyst formation (p 0.05), but higher doses led to reduced blastocyst development (p < 0.01). These findings suggest that the benefits of HIF1A stabilization are specific to the maturation phase, likely by supporting cumulus-oocyte interactions critical for establishing developmental competence, rather than by directly influencing fertilization or early cleavage. These findings highlight the potential of fine-tuned HIF1A modulation to improve IVP efficiency. Further studies should elucidate the downstream molecular mechanisms and assess post-transfer development outcomes.
Gübeli et al. (Tue,) studied this question.