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Increasing the expression of certain developmental genes at precise times in the uterus might improve the success rates for in vitro fertilization-embryo transfers (IVF-ET), according to a new study from Cincinnati Children’s.
The study, led by Sudhansu K. Dey, PhD, director of the Division of Reproductive Sciences, was published online Nov. 17 in Developmental Cell.
The genes Msx1 and Msx2, which play integral roles in organ formation during fetal development, also are essential to placing the uterus in a receptive phase needed for successful embryo implantation. Compromised uterine receptivity is a major cause of pregnancy failure in IVF programs, Dey says.
Babies successfully conceived through IVF also face a higher risk of premature birth, which can result in various health risks for the child. Identifying essential molecular signaling pathways at critical stages of early pregnancy in IVF patients could lead to new approaches for optimizing pregnancy outcome.
“Our findings raise the possibility that clinicians may be able to develop new strategies to improve implantation rates in IVF programs by temporarily increasing uterine levels of Msx,” says Dey. “This could allow clinicians to potentially extend the window of uterine receptivity and grant transferred embryos more time to implant.”
Through a series of experiments using genetically engineered mice, the researchers determined how the loss of Msx genes interferes with reproduction. Without Msx, uterine luminal epithelial cells fail to assume a slit-like architecture that forms a crypt ( or nidus) necessary for placing the embryo for successful implantation.
Mice without the Msx1 gene produced either smaller than normal litter sizes or no litters at all, while deleting Msx1 and Msx2 genes resulted in complete infertility.
In humans, gene analysis has shown that Msx genes are differentially expressed in the uterus during the menstrual cycle. This suggests that the genes identified in the mouse study also may play important roles during human implantation.
The findings also show that Msx genes maintain uterine receptivity without altering ovarian hormone levels or uterine sensitivity to these hormones. This implies that Msx also may be useful in developing non-steroidal contraceptives, Dey says.
Further investigation is warranted to apply the findings to human fertility, Dey says.
These images, published in Developmental Cell, illustrate the role Msx plays in embryo implantation.
Confocal microscope images from the study in Developmental Cell illustrate how lack of Msx gene expression makes surface cells in the mouse uterus unreceptive to embryo implantation. The bottom image shows that loss of Msx results in polarized, tightly formed columnar cells unreceptive to implantation. The top image shows a more relaxed structure receptive to successful implantation.
Sudhansu K. Dey, PhD.
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