The ultrastructural nature of human oocytes’ cytoplasmatic abnormalities and the role of cytoskeleton dysfunction

Egg quality is a limiting factor of female fertility and assisted reproductive technology (ART) success. Oocytes recovered from hyperstimulated ovaries often display morphological anomalies suspected to compromise their fertilization and developmental potential. Knowledge of (ab)normal oocyte’s intracellular organization is vital to establish reliable criteria for morphological evaluation of oocytes intended for in vitro fertilization (IVF). Here, we investigated the fine morphology of 22 dysmorphic IVF oocytes exhibiting different types of cytoplasmic irregularities, namely (1) refractile bodies, (2) centrally-located cytoplasmic granularity (CLCG), (3) smooth endoplasmic reticulum (SER) disc, and (4) vacuoles. Transmission electron microscopy (TEM) revealed the structural basis of these aberrations and indicated that the underlying cause of two of the studied morphotypes was inordinate organelle clustering. To address the mechanism required for accurate organelle positioning, we used cytoskeleton-targeting chemical compounds and performed a series of inhibition experiments involving a total of 133 human oocytes maturing in vitro. Fluorescence and electron microscopy showed that disruption of actin, not microtubules, led to the aggregation of subcellular structures resembling the morphological pattern seen in abnormal oocytes. These results imply that actin serves as a regulator of organelle distribution during human oocyte maturation. The ultrastructural analogy between dysmorphic eggs retrieved in IVF cycles and oocytes, in which actin network integrity was perturbed, suggests that dysfunction of the actin cytoskeleton might be implicated in generating common cytoplasmic aberrations. Knowledge of human oocytes’ inner workings and the origin of morphological abnormalities is a step forward to more objective egg quality assessment in clinical practice. SUMMARY SENTENCE Ultrastructural analysis of eggs exhibiting cytoplasmic abnormalities combined with inhibition experiments indicates that dysfunction of the actin network might be involved in the development of oocyte dysmorphisms.