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HEREDITIC MORPHOLOGY
IN HUMAN EMBRYOLOGY
Ke-Hui Cui M.D., Ph.D.
Savannah, Georgia, 31405, U.S.A.
August 25, 2023
Email: khcui72@hereditics.net
Pregnancy rate is closely related to embryonic quality. Embryonic quality mainly depends on the following three factors:
1. Environment influence the embryonic cytoplasmic quality.
Although cytoplasmic structures such as microtubules, centrioles, centrosomes, and cell cycle checkpoints are not genetic or epigenetic elements themselves, they play essential roles in regulating embryonic morphology and development. These components can be influenced by environmental factors (such as culture medium composition, temperature fluctuations, laser-induced damage, cryoprotectants, enzymatic activity, and human manipulation) leading to heritable cytoplasmic changes in cellular behavior and structure. We refer to these non-genetic, non-epigenetic, yet heritable influences as "cytohetic" changes. Importantly, such cytohetic alterations can precede—and potentially induce—downstream genetic (e.g., spindle missegregation, chromosomal instability) and epigenetic changes in developing human embryos. Cytohetic cascade may be: Environmental change --> cytohetic change --> spindle missegregation --> chromosomal instability (aneuploid cell) --> Epigenetic consequences. The direction of this Cytohetic cascade do not follow the direction of Centrol Dogma of Molecular Biology (DNA -> RNA -> protein) at the beginning because environment may easily influene the cell to cell heredity at the embryonic stage.
2. Different embryos contain different quality of checkpoint system.
3. Genetic factors are related to mother's age and father's sperm quality.
Hereditics includes Genetics, Cytohetics, Epigenetics and Epicytohetics.
Hereditic morphology (or H morphology) is the application of hereditic knowledge to human embryonic morphology in order to assess the embryonic growth potential. It has been described in Cytohetics that embryonic cell division and subsequent development are regulated by the cell cycle checkpoint system, often referred to as the heredity control system, within these cells. If the cells are aneuploidy, they may display abnormal cellular morphology and could potentially develop more slowly than normal cells, or cease developing altogether. According to Genetics, aneuploid cells can not be recognized by traditional morphology. However, according to Hereditics and Cell Anatomy, aneuploid cells can be recognized by Hereditic morphology with the above three points and related hereditic theory. The study of heredity (Hereditics) also encompasses Epicytohetics, which is closely related to the polarity of individual cells and the overall embryonic polarity established through cell-to-cell connections and spatial cell positioning. This Hereditic method aims to provide a more holistic and non-invasive alterntive for selecting viable embryos with true developmental competence, potentially reducing the risk of discarding viable embryos due to mosaicism or testing errors in PGT-A. The above sentences explain why the term Hereditic Morphology is used instead of the static concept of Cell Morphology or the gene-centered approach of Genetic Morphorlogy.
It has been explained in Cytohetics:
In human embryos, the cell cycle checkpoint and licensing systems are intrinsically unbalanced (Figure 1). The expression of cell cycle inhibitors—represented on the left side of the regulatory balance—is relatively low, whereas key activators such as cyclin-dependent kinases (CDKs) and cyclins, shown on the right side, remain highly active during early embryogenesis. These CDK–cyclin complexes act as cell cycle activators, driving DNA replication and cell cycle progression even under conditions of incomplete checkpoint control. This permissive state facilitates the formation of aneuploid and polyploid cells. (At the blastocyst stage, syncytial cells—those in which nuclear and genetic replication occurs without cytokinesis—are frequently observed.) Such cells are characteristic of early human embryonic physiology and represent adaptive cytoplasmic responses to the developmental environment, enabling rapid inner cell mass differentiation and early trophoblastic villi formation, thereby optimizing implantation and nutrient exchange.
Figure 1. The unbalanced checkpoints in human embryogenesis.
Most of the aneuploid cells in human embryos do not retain long-term hereditary characteristics after implantation into the maternal endometrium. This is due to the highly coordinated heredity control system within the cytoplasm, which re-establishes a normal regulatory balance and halts mitotic exit in aneuploid cells. Consequently, the proportion of aneuploid cells declines markedly during fetal development and eventually disappears from the newborn’s blood. This explains why Embryonic Genetics differs from Fetal Genetics and Postnatal (after-birth) Genetics. The genetic characteristics at these three stages are distinct because the activities of the components within the cell cycle checkpoint and licensing systems differ across these developmental stages. The transition from a mosaic embryo to a genetically normal baby across these three developmental stages represents a normal physiological adjustment of the heredity control system governed by cell cycle checkpoints. In other words, this process reflects how a normal human develops, rather than any “self-correction” event of pathological mosaicism. True pathological conditions arising from an abnormal checkpoint system cannot be self-corrected; instead, they may lead to genetic disorders or cancer, as explained by Hereditics.
Can aneuploid cells at the embryonic stage be recognized under the microscope? Under certain conditions, the answer is “Yes.” This is why Hereditic Morphology can be applied in IVF laboratories. Selected embryonic images are presented here to illustrate how human embryos can be scored to evaluate their potential for future heredity and developmental competence.
In Figure 2, based on Cell Morphology, three abnormal cells are identified. However, this image does not provide direct genetic information, and Genetic Morphology cannot be applied. According to Hereditic Morphology, none of the three cells possess the potential for further heredity. The number of heritable cells is zero. The conclusion is that the embryo is degenerated, with zero viable (living) cells.
According to Hereditic Morphology, cytoplasmic change of the embryonic cells will lead to genetic changes and will reduce the ability of cell to cell heredity (i.e. cell heritability).
Fragment
Fragments in the human embryos are easily to be seen. More fragments are related the worse cell to cell heredity which is the basic knowledge of human Embryonic Morphology. It is know that astral microtubules connect cell membrane and centrosome.