A large number of couples are infertile and in many cases IVF is not successful and there are repeated failures. In a latest development, Mumbai-based researchers have shown the molecular features of embryo–endometrium crosstalk that helps in embryo implantation.
The team led by Dr. Deepak Modi from ICMR’s National Institute for Research in Reproductive Health (NIRRH) has discovered that the endometrium is not a passive tissue which readily promotes embryo implantation but undergoes extensive remodelling brought about by the embryo at the time of implantation.
They discovered that a protein OVGP1 is induced in the endometrium precisely at the time when the embryo has to implant. That the embryo can implant only during a narrow window is well known. Studies carried out in mouse models showed that OVGP1 protein is expressed for a brief period that coincides with the time of implantation. It is known that the pregnancy hormone — human chorionic gonadotropin (hCG) produced and released by embryos is crucial for the implantation process.
The role of hCG hormone in inducing the endometrium to produce the OVGP1 protein became clear when the researchers studied the role of different hormones on endometrial cell lines. The cell lines were exposed to progesterone, estrogen and human chorionic gonadotropin hormone. “We found the hCG hormone induced the expression of OVGP1 protein. Progesterone and estrogen, too, had a role, though minor, whereas hCG had a major role in the expression of OVGP1. This tells that embryos signal the endometrium to express OVGP1,” says Dr. Modi, who is the corresponding author of a paper published in the Journal of Assisted Reproduction and Genetics.
To study how the protein helps in the implantation process, the researchers silenced the expression of the protein in the endometrium cell lines. They found that the expression levels of integrin proteins, which are essential for implantation, were significantly reduced in OVGP1 silenced cells. Similarly, homeobox protein HOXA10 levels too reduced significantly as did the cytokines, says Saniya Laheri from the Department of Biological Sciences, NMIMS Sunandan Divatia School of Science, Mumbai and first author of the paper.
“We found the OVGP1 protein is required for balancing the expression of genes required for implantation,” says Laheri. “We then wanted to test if the expression of the altered genes affects implantation.”
For implantation to take place the trophoblast cells (the outermost layer of the embryo) have to adhere to the endometrial epithelial cells. When the OVGP1 protein was silenced in the endometrium the adhesion of the trophoblast gets reduced. “This led us to conclude that OVGP1 in the endometrial epithelial cells is required for embryo implantation,” says Nancy Ashray from NIRRH, a co-author of the paper.
Women who had repeated IVF failure apparently had reduced levels of OVGP1 protein. “The levels of OVGP1 are reduced by 30% in women with repeated IVF failure,” Laheri says.
“This is a very fundamental research and we are now beginning to understand how the embryo and endometrium have to crosstalk. This work in long term might have implications in management of infertility,” says Dr. Modi.
