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FORUM: IS ARTIFICIAL OOCYTES AS GOOD AS NATURAL OOCYTES?
Historical Bases of Hereditics:
Series of comments on mitochondrial replace therapy, stemcell and CRISPR for human reproduction. Quoted from ivf.net
Shail K Chaube Institute of Science, Banaras Hindu University, Varanasi
Does oocyte generated from Oocyte like stem cell/neo-oogenesis/adult oogenesis is as good as natural oocytes?
Question. Asked October 12, 2021
Our long standing understanding for mammalian ovary is that it has fixed number of germ cells and duty of the ovary is to ovulate high quality ovum for successful fertilization and early embryonic development. However, growing studies suggest that the oocytes can be generated from Oocyte like stem cell/neo-oogenesis/adult oogenesis and fertilized in vitro. Therefore, it is important tom know whether oocytes generated from these sources are as good as the follicular oocytes collected from mammals under natural conditions. Kindly give your opinion on the genomics, proteomics and metabolomics aspects of ocytes generated from Oocyte like stem cell/neo-oogenesis/adult oogenesis.
Ke-Hui Cui added an answer October 12
Hereditics is an academic subject of heredity to study how to keep stable heredity of a species, such as how to keep human beings to be a stable species in heredity. Heredity is decided not only by genes (or DNA), but also by normal cytoplasm and normal herdity control system. Artificial oogenesis harms cytoplasm and heredity control system by many different kinds of factors. Thus artificial oogenesis will lead to subhuman reproduction with many different kinds of artificial cytohetic diseases in future children. Please learn Hereditics, Cytohetics and Epicytohetics in https://www.hereditics.net to understand new concept of Genetics and how cycles of "natural selection, evolution and heredity" to keep a species to be stable. The theory of Hereditics is a new and very deep theory. Preface is the outline of the theory. "Hereditics and Origin of Life" is one of the chief educational course. Only Hereditics may be used to explain correctly about what a correct concept of Genetics is.
Shail K Chaube added an answer. October 12
Dear Dr. Ke-Hui Cui, hope you might have read my question carefully. While giving your opinion, kindly focus on the question only.
I agree with You Dr. Cui. Cytoplasm and DNA both plays the role
Dear Dr. Juneja, your detailed opinion/ reply to my question is most welcome.
Ke-Hui Cui added an answer. October 13
Hereditics Leads To New Cognition Of Genetics And Genomics
Dear Dr. Chaube,
I comprehend that you did not cognize the content of hereditics.net and thought my answer to be out of your question.
Your question is whether the artificial oocytes to be good as natural oocytes or not. To answer your question, only to use knowledge of genomics, proteomics and metabolomics is not enough. Genomics has been misunderstood as the unique study of heredity for a long time, because genes and DNA are related to heredity. If artificial oocytes might keep the heredity as the same as the natural oocytes do, the artificial oocytes might have been as good as the natural oocytes. However, heredity is not only depend on genes and DNA. Covid 19 virus contains genes and DNA. The research of genes of virus Covid 19 is a kind of research of Genetics without characteristics of heredity. No heredity means the virus to be easily mutate in new species. The researh of Genetics is not absolutely related to heredity. Genome of virus does not have heredity because virus is lack of cytoplasm and heredity control system.
Also, preimplantation genetic testing for aneuploidy of human embryos contain a lot of "aneuploid" embryos and mosaic embryos. These "abnormal embryos" with abnormal genome (diagnosed by the most advanced and correct PCR techniques) were tranferred. They all showed that the precisely and correctly diagnosed abnormal genome in human do not contain heredity, and the babies were all (>99.9%) karyotyping normal. They are not false positive results but the normal results of normal functioning of the heredity control system (cell cycle checkpoint and licensing system) in every embryonic cells. Thus, to understand the function of cytoplasmic heredity and heredity control system which are explained in Hereditics and Cytohetics in hereditics.net will be the theoretical bases to answer your question. Genes or DNA is only one of four components in heredity.
According to Epicytohetics: any thing changes embryonic cytoplasm especially ooplasm will lead to change of heredity and future abnormal functions of different organs and tissues in future babies. Cytopalsm is also important hereditary materials according to Hereditics. Artifical oocytes do not contain the same cytoplasm as the natural ooplasm. Artificial oogenesis harms cytoplasm and heredity control system by many different kinds of factors. Artificial oocytes will lead to subhuman reproduction. "Hacking Darwin" for genetic engineering in human reproduction which including artificial oocyte for human reproduction is a kind of thinking lack of scientic bases when facing the theory of Hereditics.
However, artificial oocytes may be very useful for future tissue cloning and organ cloning (or called stem cell) as a tool for medical treatment in regeneration medicine, because they will not change human heredity if not to be used as germline for human reproduction. The principle is: ban subhuman reproduction before going ahead for tissue and organ cloning.
Dr. Chaube, You are doing quite good to make clear your question of future research. Thank you for your feedback and discussion.
Ke-Hui Cui, M.D., Ph.D.
Shail K Chaube added an answer. October 14
Thank you Dr. Ke-Hui Cui M.D., Ph.D. for your personal opinion on introducing a new concepts of Hereditics, Cytohetics and Epicytohetics and considering both egg yolk and egg white as hereditary material. We know that the cytoplasmic inheritance (specially through mitochondrial genome) play important role in determining the fate of the individual (in mammals). I would not comment on your new concept and feel that it is premature to say anything on these new thoughts.
Whatever the research experience I have got on oocyte biology in last 30 years, I believe that the mammalian oocyte is a specialized cells and takes very long time (few oocytes takes very long time from puberty to menopause almost 30 years) to complete (oocyte maturation process; both nuclear maturation as well as cytoplasmic maturation in order to ensure the fully competent oocytes required for successful fertilization, early embryonic development and fate of the individuals).
As you know the mammalian oocytes are microlecithal with little or no yolk. However, mature human sperm are highly compact with no cytoplasm in the head region. As you know that the animal cloning for the first time Prof. Sir Ian Wilmut cloned Dolly and now several mammalian species have successfully been cloned using somatic cell nuclear transfer (SCNT) method. Keeping all these into consideration, I wonder how much these new concepts fit into specially in mammalian oocytes and helpful in oocyte biology of mammals.
Good luck for your new journal "Hereditics" in future.
Ke-Hui Cui added an answer. October 14
HEREDITY PATTERNS AND DAMAGES
Dear Dr. Chaube and Dr. Juneja,
Now all three of us agreed "cytoplasmic inheritance", and "cytoplasm and DNA both plays the role" in heredity. Small difference is: Dr. Chaube is focusing more on mitochondrial genome, and Dr. Juneja and I are focusing not only on mitochondrial genome but also on heredity control system with centrosome and other cytoskeleton structure as well. Gregor Mendel took 16 years for people to recognized the concept related to heredity which was named as "gene" later. It seems that we might need another 12 (i.e.16 - 4) years for people to comment in mature manner on the three new concepts (Hereditics, Cytohetics and Epicytohetics) after popularization of basic knowledge of cell cycle checkpoint, licensing system, centrosome and centrioles in younger generation.
All mammalian oocytes contain genome (DNA) althought not like yolk color (yellow) but equal to egg yolk DNA. Their ooplasm also contains important scattering hereditary control material (γ-tubulin). Mature human sperm contains very little amount of cytoplasm which includes very important hereditary materials - two centrioles. A well-defined proximal centriole is present next to the basal plate of the sperm head, while the distal centriole gives rise to the central strand of the sperm tail flagellum. About different inheritance patterns in genes and in cytoplasm, please read "Control overpopulation and prohibition of subhuman reproduction" in hereditics.net.
In the same webpage, the paper also explained: Why somatic cell nuclear transfer (SCNT) got only 1-3% birth rate which is greatly different from natural fertilization with natural oocytes. First, deficiencies in genome reprogramming cause problems in DNA methylation and histone modification. Second, SCNT damaged heredity control system in ooplasm during nuclear transfer procedures. (Please read "Abnormal Cell Anatomy of MRT subhuman beings" in the same website.)
In the same webpage, the paper explained that an intact cytoplasm is a very important determinant for normal differentiation
The levels of damage of cytoplasm and results are summarized as:
Mild: Repeated temperature change and laser radiation by PGS – influence on mental development, called "Embryo Biopsy Syndrome" in hereditics.net.
Medium: Oocytoplasm transfer – accidents and incidences; other neuropathy and immune problems, called "Mitochondrial Replacement Therapy Syndrome" in hereditics.net.
Heavy: Spindle transfer and PNT – embryo growth arrest, stillbirth, early death, infertility, etc., also called "Mitochondrial Replacement Therapy Syndrome" in hereditics.net.
Very heavy: SCNT – extremely low birth rate, babies with a lot of health problem;
Very very heavy: Damaged centrosome or centrioles – Heredity stops.
The more damage of cytoplasm, the lower birth rate with more and severer health problems until heredity stops.
Birth does not mean normal heredity with healthy offspring. Artificial oocytes will produce subhuman beings with new cytohetic diseases. As animal reseach aiming at future haman practice, artificial oocytes is not as good as natural oocytes.
Ke-Hui Cui, M.D., Ph.D.
Dr. Ke-Hui Cui M.D., Ph.D., the cytoplamsmic inheritance is very well established in genetics and being taught to the undergraduate course in India. The cytoplasmic inheritance comes specially in animal cells from mitochondrial genes. I am not focusing on mitochondrial genome. I work on oocyte biology specially on the roles of signal molecules on cell cycle proteins (Cdks and Cyclins), oocyte meiosis (from diplotene arrest to M-III like arrest), cell cycle check points (diplotene arrest, M-I arrest, M-II arrest, M-III like arrest). In addition, we are also focusing on various death pathways involved in germ cell depletion from ovary including apoptosis, autophagy, necroptosis etc. Further, impact of stress on oocyte biology is also the current focus area). The impact of ROS, oxidative stress on mitochondria distribution and MMP in oocytes are also being investigated.
Since mammalian oocyte meiosis takes very long time in order to release competent ovum for successful fertilization, any minor changes during the achievement of meiotic competency may lead cause defects at the level of genomics, proteomics and metabolomics that ultimately results in the ovulation of poor quality ovum. The poor quality oocytes may generate abnormality during early embryonic development and fate of the individual. Hence, it is very important to ensure the good quality of oocyte is being ovulated to prevent any such pathological conditions and congenital problems.
Yes, I agree that the oocytes generated through neo-oogenesis, adult oogenesis or from oocyte like stem cells may not be as good as oocytes that are matured after taking such long period (both nuclear as well as cytoplasmic maturation= full maturation) that are fully competent for fertilization/early embryonic development. Hence, my question is timely and important to understand and discuss ....the importance of oocyte quality that directly impact the fate of the fertilization/ early embryonic development as well as fate of the individual.
Since I do not find any published paper on your concepts in cited link: hereditics.net, I would love to read recent papers on your science published in reputed, peer reviewed international journals to know these new concepts.