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bioRxiv · 10.64898/2026.06.18.733271

Holotomography reveals biophysical remodeling of mouse oocytes during post-ovulatory aging

Kim, M.·Lee, C.·Do, J.·Shin, T.·Iliev, D.·Choi, K.·Shin, S.·Ko, J.·Popa, T.·Hickman, C.·Kim, J.·Park, Y.
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Abstract

Routine assessment of oocyte state in reproductive biology and clinical embryology still relies largely on two-dimensional transmitted-light morphology, leaving the underlying three-dimensional intracellular organization largely unmeasured. Here, we use holotomography to reconstruct volumetric refractive index (RI) distributions in unlabeled live mouse oocytes and combine this imaging with sparse-annotation, AI-assisted compartment segmentation and multidimensional feature extraction across geometry, RI statistics, dry-mass density, and intracellular texture. Applied to an in vitro model of post-ovulatory aging, holotomography-derived biophysical profiles separated fresh and aged oocytes more strongly than two-dimensional brightfield-derived features, and feature-family ablation indicated that non-morphological descriptors contributed substantially to this separation. At the population level, aged oocytes showed coordinated ooplasmic remodeling, including reduced volume, increased RI heterogeneity, and increased dry-mass density while total dry mass was broadly conserved. These findings demonstrate a label-free quantitative framework for detecting post-ovulatory aging-associated biophysical remodeling in intact mammalian oocytes. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/733271v1_ufig1.gif" ALT="Figure 1"> View larger version (89K): org.highwire.dtl.DTLVardef@c7257aorg.highwire.dtl.DTLVardef@6d92f0org.highwire.dtl.DTLVardef@1c9f7eborg.highwire.dtl.DTLVardef@b36637_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Kim, M., Lee, C., Do, J., Shin, T., Iliev, D., Choi, K., Shin, S., Ko, J., Popa, T., Hickman, C., Kim, J., Park, Y.. 2026-06-19. Holotomography reveals biophysical remodeling of mouse oocytes during post-ovulatory aging. https://doi.org/10.64898/2026.06.18.733271

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