Improving IVF Success

SUMMARY
Maybe tissue matching tests between the ovum donor and the surrogate host can improve in virto fertilization (IVF) surrogate host success rates.

It has been shown [1] that during the gestation of a mammalian female embryo, in every cell only one of the X chromosomes has active genes participating in the biochemistry of that cell. This is also likely to be the case in every cell throughout the life of any female mammal. The reason for this is as follows. If genes from both X chromosomes are active in a cell, then for each gene twice as much biochemistry would take place in a cell of a female than in a male, which has only one X chromosome. This excess of biochemistry would almost certainly be fatal.

How is the unwanted activity of an entire X chromosome’s genes in a female cell controlled? In the first cell, the fertilized ovum, only the maternal X chromosome’s genes are active. The mechanism that signals the cell to use the maternal X chromosome to manufacture RNA from the chromosome’s DNA are epigenetic marks (e.g., histone modifications and polycomb proteins) which are attached to the maternal X chromosome during a stage in the development of the ovum from a premature oocyte [2]. The sperm chromosomes do not receive these marks. The paternal X genes remain inactive until the fetal inner cell mass forms, and in this structure the differentiation of the tissues of the fetus proper begin. That is, until the inner cell mass forms, each successive cell generation copies the epigenetic marks for the maternal X chromosome as the maternal X chromosome's DNA itself is copied during mitosis. In the inner cell mass, the copying of these marks ceases, and instead epigenetic marks are randomly placed on either the paternal X chromosome or the maternal X chromosome, but not both, as the X chromosomes are copied during mitosis. By this mechanism each inner cell mass fetal cell randomly has either the paternal X genes or the maternal X genes active, and this mechanism can continue throughout the life of the female mammal.

I suggest the following as a possible explanation for the evolution of the maternal marking mechanism. While the paternal X genes are inactive, the placenta is formed. This guarantees that only maternal genes participate in the development of the placenta. If paternal genes from the fetus participated in the development of the placenta, then there would be a possibility that the placenta tissues created by the uterus and carrying the mother’s blood supply might have a allergic rejection reaction to the fetal placental tissue, perhaps like a skin transplant rejection. Such a rejection would likely manifest itself as a miscarriage or even perhaps as a failure to implant the blastula into the uterus wall. If this is the case, then it is plausible that during the early evolution of mammals, the random choice of maternal or paternal X chromosome activity starting with the first mitosis may have been the controlling mechanism for the first placental mammals, and the maternal marking mechanism evolved later as a reproductive improvement that avoided miscarriages.

If my conjecture about maternal X chromosome marking is correct, then there is an implication regarding in vitro fertilization (IVF) with host surrogate mothers. The active genes of the maternal X chromosome of the blastula implanted into a host surrogate mother might result in the same kind of allergic rejection that would occur if the paternal X genes were active. In the clinical use of IVF, this might be noticed as a significantly larger fraction of miscarriages or implantation failures with host surrogate IVF implantations as compared with natural surrogate IVF implantations. In natural surrogate IVF implantations, the ovum fertilized in vitro is implanted into the uterus of the same woman who produced the ovum. Therefore, in this case, no allergic rejections would occur.

If it should be confirmed that host surrogate IVF implantations result in a higher rate of miscarriages and implantation failures than natural surrogate IVF implantations, then it may be possible that immunological tissue matching rejection tests between ovum donor and host surrogate may result in reducing miscarriages and failed implantations.

REFERENCES
[1] Epigenetic Dynamics of Imprinted X Inactivation During Early Mouse Development
Ikuhiro Okamoto, Arie P. Otte, C. David Allis, Danny Reinberg, Edith Heard
SCIENCE Volume 303, Number 5658, Issue of 30 Jan 2004, pp. 644-649.

[2] Japanese Scientists Create Fatherless Mouse
Gretchen Vogel
SCIENCE Volume 304, Number 5670, Issue of 23 Apr 2004, pp. 501-503.

COPYRIGHT NOTICE This document is copyright © 2004 by Buzz Bloom. All rights reserved.
It may be freely copied, reproduced, forwarded, and/or distributed in electronic form for personal and educational purposes provided you copy, reproduce, forward, and/or distribute it in its entirety. This means that all copies must include the following: the copy permission statement, this copyright notice, the Buzz's Place website title, and the full text of the document including the title, the author's name, and the date.

This document may not be distributed for profit or reproduced in printed form or in any edited form without the author's consent. A document may be distributed with a clearly distinct and separated appendix with notes and comments where the appendix has a clearly separate attribution of authorship.
You may contact the author using the comment space on the home page of the Buzz's Place website:
http://users.rcn.com/bbloom/

HOME
BACKGROUND