Is Human Parthenogenesis Possible?

Is Human Parthenogenesis Possible?

     The intent of this post is to investigate what parthenogenesis is in relationship to the microbiological aspects in mammals including whether viable human offspring could potentially be produced via parthenogenesis, given the current state of technology. This post is NOT about whether human parthenogenetic birth should occur, nor is it intended to address distortion of the definition of parthenogenesis, including whether technological manipulation, artificial means, or some method is disqualified from being classified as parthenogenesis. Lastly, the term "virgin" or terms associated with virgin such as "immaculate" have no concrete definitions and are surrounded by mystique, emotion, cultural bias, and frequently non-scientifically based belief (Gillis-Buck, 2016), therefore, although layman-speak often mixes up and allows for the substitution of the terms parthenogenesis and virgin, I do not believe it is proper to include the word virgin (or associated words) in a scientific discussion on parthenogenesis and will not discuss this etymological exchange, despite the fact that a number of published papers include this "catch phase". I do welcome a healthy and courteous exchange on the history, microbiology, methodology, analysis, insights, advances, and other molecular biological aspects of this incredibly fascinating area of science.

     The definition of parthenogenesis is reproduction involving only a female gamete, without involvement, intervention, or "fertilization" by a male gamete. Parthenogenesis occurs widely in nature across thousands of species in numerous phylums including but not limited to Chordata, Rotifera, Arthropoda, Nematoda, and Tardigrada (Jaron et al., 2021). The pursuit of human parthenogenetic procreation has been of interest since at least 1770, however a lengthy and thorough search through history has uncovered no occurrence of parthenogenesis in the Mammalia class (Gillis-Buck, 2016). Recent experiments and studies are uncovering and circumventing many of the molecular barriers that prevent mammals from successfully producing offspring by parthenogenesis. An experiment by Bos-Mikich (2016) describes how unfertilized oocytes cease development in metaphase II due to the lack of a rise in Ca2+ levels. Development remains arrested until the oocyte either becomes fertilized by spermatozoon or is stimulated by an artificial agent such as ethanol and a secondary agent. It is noted in the paper that the activation method varies between species. Bos-Mikich (2016) also discusses a second barrier to successful full-term development called genomic imprinting whereby genes on sister alleles are turned off or imprinted based on opposing parental donor epigenetics, leaving one allele able to be transcribed.

     As mentioned previously, parthenogenesis is inherent throughout the animal kingdom. A singular female germ line in some vertebrate species can be totipotent, producing offspring. The same is not known of the male germ line (Mann, 2001; Condic, 2014). In addition to a common set of gene expressions needed for embryo development, there are specific genes products that control the development of each sex, depending on the stage of development (Barlow & Bartolomei, 2014; Mann, 2001). Given that heterosexual germ line contributors each supply alleles of genes on sister chromatids and that expression of both alleles could produce too much of a gene's product or interfere in development, nature has implemented epigenetic controls to regulate which alleles on which chromatids are transcribed under varying developmental contexts (Bos-Mikich, 2016). Thus, the second barrier to full term parthenogenetic development occurs when only one set of genomic imprinting from one gender exists such as in dual female epigenetic contributions (both alleles are active in both sets from both female contributors). It causes too much expression of some genes and no expression of other necessary genes (Bos-Mikich, 2016).

     Part of this elaborate, multi-modal epigenetic scheme includes genomic imprinting which disables, or imprints, genes through methylation of areas such as those need to promote or start transcription, inhibit transcription, or skip transcription through chromatic partitioning (Mann, 2001). Genomic imprinting epigenetics are inherited, one set of imprints originating from each gender's germ line. In this way at the point in development where the sex of the embryo is established, gene expression particular to that sex can be activated based on the epigenetics passed on from the appropriate germ line (Barlow & Bartolomei, 2014; Mann, 2001). It is believed that some genomic imprinting also controls for genes needed for proper placental development (mammalian), attachment, nutritional support, and other areas critical to developmental (Obata & Kono, 2002). The numerous genes and alleles involved in genomic imprinting are still being identified (Barlow, & Bartolomei, 2014; Jirtle, 2012).

     Genomic imprinting of the clustered gene promoters for H19 and insulin like growth factor-2 receptor (Igf2r) were identified early in the search for a parthenogenetic solution (Barlow & Bartolomei, 2014; Mann, 2001). In 2004, Kono et al. surprised the world by reporting that they had successfully brought a mouse with dual maternal germ lines to full term, adulthood, and that it mated successfully with no aberrant affects noted in the subsequent generation (Kono et al., 2004). They accomplished this by deleting 13 kb of the H19 gene in one of the parent mice. Although there were a number of failed developments, two of the embryos survived to adulthood. It was found that with the H19 gene knocked out, a somewhat normal cascade of developmental gene expression followed, enough to bring the two mice to full term (Kono et al., 2004). Within the past year another significant advance was reported by Wei et al. (2022) who brought bimaternal parthenogenetic embryos to full term by modifying the methylated epigenetic controls of seven genomic imprinted regions. Given the continued successful advances in the effort to bring parthenogenesis to fruition in mammals, I believe that within a few years, we may see near 100 percent successful technical capability to produce parthenogenetic humans if humanity so desires.

References

Barlow, D. P., & Bartolomei, M. S. (2014). Genomic Imprinting in Mammals. Cold Spring Harbor Perspectives in Biology, 6(2), a018382. doi.org/10.1101/cshperspect.a018382

Bos-Mikich, A., Bressan, F. F., Ruggeri, R. R., Watanabe, Y., & Meirelles, F. V. (2016). Parthenogenesis and Human Assisted Reproduction. Stem Cells International, 1970843. doi.org/10.1155/2016/1970843

Condic M. L. (2014). Totipotency: What it Is and What it Is Not. Stem Cells and Development, 23(8), 796–812. doi.org/10.1089/scd.2013.0364

Gillis-Buck, E.M.(2016). Redefining "Virgin Birth" After Kaguya: Mammalian Parthenogenesis in Experimental Biology. Catalyst: Feminism, Theory, Technoscience,2(1), 1-67. doi.org/10.28968/cftt.v2i1.28826

Jaron, K. S., Bast, J., Nowell, R. W., Ranallo-Benavidez, T. R., Robinson-Rechavi, & M., Schwander, T. (2021). Genomic Features of Parthenogenetic Animals. Journal of Heredity, 112(1), 19–33. doi.org/10.1093/jhered/esaa031

Jirtle, R. (2012). Geneimprint: Imprinted Gene Databases. Retrieved on September 10, 2022 from www.geneimprint.com/site/genes-by-species.Homo+sapiens

Kono, T., Obata, Y., Wu, Q., Niwa, K., Ono, Y., Yamamoto, Y., Park, E. S., Seo, J. S., & Ogawa, H. (2004). Birth of Parthenogenetic Mice that can Develop to Adulthood. Nature, 428(6985), 860–864. doi.org/10.1038/nature02402

Mann J. R. (2001). Imprinting in the Germ Line. Stem Cells, 19(4), 287–294. doi.org/10.1634/stemcells.19-4-287

Obata, Y., & Kono, T. (2002). Maternal Primary Imprinting is Established at a Specific Time for Each Gene Throughout Oocyte Growth. The Journal of Biological Chemistry, 277(7), 5285–5289. doi.org/10.1074/jbc.M108586200

Wei, Y., Yang, C. & Zhaoa, Z. (2022). Viable Offspring Derived from Single Unfertilized Mammalian Oocytes. Proceedings of the National Academy of Sciences of the United States of America, 119(12). doi.org/10.1073/pnas.2115248119