Fig. 7. The fecundity structures in patient HGSC tumors.

A Patient tumor tissues contain histologic structures similar to the type 1 and type 2 organoids. a type 1 organoid-like tissue structure. b–d Type 2 organoid-like tissue structure at different stages of the giant nucleus with partially or entirely cellularized small nucleus. Black arrows: giant nuclei of the host cells. Cyan arrows: fecundity cells. Green arrows: cell colonies formed by the released fecundity cells. Bars equal 20 μm. B The estimated c-value (DNA content) of the nuclei showing in A. The measurements of the group a were performed with an uncropped image. The measurements for groups b–d include the nuclei within the areas confined by the dotted lines. The ploidy level was calculated based on the average nuclear sizes following the formula for the volume of an ellipsoid: (Vn = (4/3)*pi*X*Y*Z), where X is the long axis of the nucleus. Ploidy level was calculated following the formula c = 2*(Vx/Vd), where Vx denotes the volume of the nucleus to be measured, and Vd denotes the average nuclear volume of the reference diploid cells. C Schematic of pre-implantation pre-embryogenesis and the life cycle of PGCC. Left panel Illustration of pre-embryogenesis in the pre-implantation embryo. Fertilization initiates nuclear cleavage (1) to generate smaller-sized blastomeres with decreased cell size and increased nuclear-to-cytoplasmic ratio (2–4). The blastomeres lose cell boundary and compact (5), become re-cellularized and form a morula (6) and further develop into a blastocyst (7). A subset of the embryoblast is set aside to develop into primordial germ cells (8) to develop into the giant egg and tiny sperm (9). The fusion of sperm with egg initiates a new round life cycle. Right Panel. The life cycle of PGCCs and cancer macroevolution. Diploid/aneuploid cells undergo asymmetric mitosis (1) and form a fecundity cell (2). The nucleus continues intracellular nuclear and cell division and nuclear fusion (3-4) and forms a giant nucleus (5), which undergoes MEM or RMEM (6,7); a subset of fecundity cells bud out, assume mitotic division, and form blastula-like organoids for microevolution (8) or resume the new life cycle of PGCCs to facilitate cancer macroevolution (9). ICM inner cell mass, N/C ratio nuclear-to-cytoplasmic ratio, PGC primordial germ cell, TP trophectoderm. The red nuclei indicate asymmetric mitosis and fecundity cell.