Biology 133 lecture AY 2021- 2022

Good day ma’am! Thank you for listening and for your questions.

(1) What ART techniques are already being applied in humans?

Assisted Reproductive Technology (ART) comprises fertility treatments wherein eggs or embryos are handled to achieve pregnancy. Some of the ART techniques that are already being applied in humans are the following (from Davis, 2021):
In vitro fertilization (IVF) - involves extracting eggs and fertilizing them in the lab
Intrafallopian transfer - uses laparoscopic surgery to transport gametes into the fallopian tube
Frozen embryo transfer - IVF embryos that were previously frozen are thawed and inserted into the uterus
Intracytoplasmic sperm injection (ICSI) - use of microinjection to inject sperm to the egg (like IVF but in IVF, sperm is not injected directly into the egg, instead, egg and sperm are left to fertilize on their own)

(2) More specifically, what do you think would be the implications of reduction of ICM cells?

ICM cells in embryos develop into extraembryonic tissues. Reduced number of ICM cells were a result of a zygote cleaving much slower than the normal rate. Since embryos with lower number of ICM cells were assumed to grow less and slower, reduced ICM cells will imply a lower weight of ART children at birth. In addition, reduced ICM cells can cause significant changes in gene expression regarding cell function, development, and metabolism (De Sebastiano et al., 2010). Moreover, the state of ICM reflects the possibility of pregnancy loss. This means that reduced ICM cells could greatly affect the outcome of the pregnancy (Giritharan et al., 2012).

(3) Please elaborate on the alteration of behavior that was mentioned as one of the consequences.

Effects in the postnatal and adult period in relation to IVC includes alteration of behavior as mentioned in the report. The study of Ecker et al. (2004) explored the behavioral consequences of embryo culture of rats and found that adults derived from cultured embryos exhibit specific behavioral alterations in the elevated zero maze and Morris water maze tasks.The results of the study showed that there are small but significant long-term alterations in the behavior of the rats such as anxiety, locomotor activity, and spatial memory and the type of culture medium has a certain effect on the degree of these changes. Their study showed that the males derived from culture embryos had decreased anxiety possibly caused by alterations in the amygdaloid or extended amygdaloid systems while the impairment in spatial memory suggests that the embryo culture may selectively alter aspects of hippocampal function required for long-term memory storage.

References:

De Sebastiano, F., Esteban, F. J., Horcajadas, J. A., Lloyd, K. C. K., … Rinaudo, P. F. (2010). Effect of ICSI on gene expression and development of mouse preimplantation embryos. Human Reproduction, 25(12), 3012–3024. doi:10.1093/humrep/deq266
Davis, K. (2021). What to know about assisted reproductive technology. Medical News Today. Retrieved from https://www.medicalnewstoday.com/articles/assisted-reproductive-technology
Ecker, D. J., Stein, P., Xu, Z., Williams, C. J., Kopf, G. S., Bilker, W. B., Abel, T., & Schultz, R. M. (2004). Long-term effects of culture of preimplantation mouse embryos on behavior. Proceedings of the National Academy of Sciences of the United States of America, 101(6), 1595–1600. https://doi.org/10.1073/pnas.0306846101
Giritharan, G., Delle Piane, L., Donjacour, A., Esteban, F. J., Horcajadas, J. A., Maltepe, E., & Rinaudo, P. (2012). In vitro culture of mouse embryos reduces differential gene expression between inner cell mass and trophectoderm. Reproductive sciences (Thousand Oaks, Calif.), 19(3), 243–252. https://doi.org/10.1177/1933719111428522

Hi Geanine, Jewell, and Ruth! Thank you for your question and your curiosity!

There are several IVF processes that cause embryonic alteration discussed in our report and findings from these can significantly help improve IVF. For instance, since several studies reported deleterious consequences of superovulation in gene expression of embryos, IVF protocols are manipulated and improved based on these consequences in order to increase IVF safety. Another example is that the article reported that pre-implantation genetic diagnosis (PGD) was found to cause short and long term behavioral disorders in mice. Due to these findings, IVF protocols may reduce PGDs or alter the procedure in a way that will cause less harm to the embryos.

Several more trials and experiments are needed in order to apply the findings of the studies in the article. Many of those studies are also conducted in animals and not yet on humans due to safety and ethical reasons. Also, many of the specific roles of environmental factors on embryo development and phenotype alterations are not yet fully understood. I think we still have a long way to go before we really achieve a ‘perfect’ IVF, but every research on this field will surely help towards IVF improvement.

Hello Niño, Kenneth and Joshua! Happy holidays to you as well!
Regarding your question, epigenetic risks and alterations have been studied insufficiently because phenotypes associated with epigenetic defects may be difficult to identify in short-term studies. In addition, phenotypes due to imprinting defects may be obvious during early life stages while other phenotypes may be subtler, such as the phenotypes of cancer predisposition that can be measured only later in life. A definite answer about the safety and practices to minimize risk of epigentic alterations caused by assisted reproduction is not certain but a long-term clinical follow up during the whole life of a child born by IVF is suggested, because epigenetic alterations in the early stages of development can be expressed later in adult life. This way conditions or diseases arising from IVF can be monitored and treated.