A step towards understanding embryo implantation

Work done in the lab of Dr. Deepak Modi at ICMR- National Institute for Research in Reproductive Health

About author

Abhishek Tiwari obtained his Bachelor’s degree in Life sciences and Biochemistry (Chemistry Honors) from the St. Xaviers’ College, Mumbai. Subsequently, he moved to the Sunandan Divatia School of Science at NMIMS University for his Masters, where he joined Dr. Deepak Modi’s lab at ICMR-NIRRH, Mumbai for his internship. Under the guidance of his mentor, he worked on the understanding of feto-maternal crosstalk during implantation and with the help of his lab mates, deciphered Epithelial to mesenchymal transition (EMT) as a mechanism of embryo implantation. The work was applauded at various international conferences with several awards. Abhishek was also awarded with the best thesis at NMIMS University for this work. He is now moving to the University of Montreal for his graduate studies in neurosciences with a faculty scholarship. He is a microscopy enthusiast who loves colorful fluorescence images, loves dancing and trekking when not at his lab bench.

ICMR- National Institute for Research in Reproductive Health

Interview

How would you explain your research outcomes to the non-scientific community?

In India, ICMR estimates that nearly 1:5 couples face difficulties in conceiving. In many such infertile couples, in vitro fertilization (IVF) is a treatment of choice for biological parenthood. However, the success rate of IVFs is very low, as many good quality embryos do not implant into the womb. This is a major hurdle because we do not understand how embryos implant into the uterus. The inner lining of the uterus is called the endometrial epithelium. It is the site where the embryo implants and establishes pregnancy. In this study, we aimed at investigating a key protein E-cadherin in the endometrial cells. E-Cadherin is responsible for cell-cell attachment in the epithelium. Using the mouse as a model, our results show that this protein molecule changes its location under the influence of ovarian steroid hormones (estrogen and progesterone) and thus regulates epithelial tissue architecture.

We got further excited when we studied the embryo while it was implanting in a pregnant mouse. We found that in the presence of an embryo, the level of E-Cad protein was reduced dramatically which resulted in a “loosened” epithelial tissue allowing the embryo to enter the walls of the uterus and “implant”. Interestingly at the same time, when the embryo is initiating to implant, another protein called N-cadherin, which is not generally expressed in the epithelium, starts to express. Occurrence of this molecule suggests a switch in epithelial cells, scientifically known as Epithelial to mesenchymal transition (EMT), where cells can start to walk around. To put this into a perspective, the endometrium is set up to receive an embryo due to the influence of steroid hormones. When the embryo enters the uterine space, it activates EMT, which causes further weakening of the epithelial barrier and thereby successfully burrowing itself into the endometrial tissue.

The endometrial epithelial cells show distinct E-Cadherin localization between the estrus and diestrus phases. This localization or sorting pattern can be recapitulated by treating the juvenile mice with steroid hormones estrogen and progesterone. In presence of an embryo, the sorting pattern is further disrupted (possibly due to cues from the embryo). Epithelium stains positive for N-Cadherin which can help the epithelial cells to “loosen up” and make way for the embryo to implant.

How do these findings contribute to your research area?

For the first time, we have been able to capture this phenomenon of EMT in mice endometrial epithelium specifically at the time of implantation. This opens our understanding of the epithelial barrier, which is not rigid but moves like a rolling gate under special conditions to aid the embryo to initiate pregnancy. These findings not only help solve fundamental questions about implantation but can also help modulate the endometrial tissue to improve the IVF rates in future.

“findings not only help solve fundamental questions about implantation but can also help modulate the endometrial tissue to improve the IVF rates in future.”

What was the exciting moment during your research?

There were multiple exciting moments as we serendipitously stumbled upon E-cad dynamic organization. Earlier pointed out by Deepak while observing the slides under the microscope, I did not believe it until I developed the 3D surface plots of epithelial cell. We are very thankful to Bobby from TIFR for lending her technical expertise in confocal microscopy using, which we could capture the phenomenon in 3D cultures of human endometrial cells. This was the most crucial point, as we did not have expertise in our Institution for this experiment. With single-cell resolution, we knew we were in for a treat, as this was a new addition to the available literature.

Another exciting moment was when we captured a beautiful embryo and the surrounding tissue showed a remarkable difference from the rest of the tissue. We thought that we had hit a jackpot, as this would add some insightful information to the textbooks.

What do you hope to do next?

Our lab is investigating the master regulator, which dictates these changes in the endometrial tissue. My friend Nancy who is developing even more colorful pictures by simultaneously capturing multiple factors involved in the story now leads the project.

At the personal level, I am moving to the University of Montreal, Canada to pursue a PhD in the field of neuroscience.

Where do you seek scientific inspiration from?

Dr. Subhas Mukhopadhyay, the father of Indian IVF research, inspires me. I admire my mentor Dr. Deepak Modi who is an excellent orator, a keen observer, and a perfectionist. I aim to graduate into their ranks and contribute to science globally.

How do you intend to help Indian science improve?

Our lab continuously focuses on promoting the research findings on the social media sites like Facebook, Twitter, etc, apart from the mainstream research portals. We make sure that we explain the crux in common man’s language. I aim to increase the inclusivity of the common people in research by opting for various methods, such as public interactions, write-ups etc. After all, we get to use taxpayers’ money for research. In addition, at the lab, we regularly discuss about various Indian scientists and women in science.

Recently, there was an exciting initiative by Deepak on celebrating the nine days of Navratri by talking about nine Indian women in STEM. We have shared this information on several social media platforms and with family and friends.

I also intend to return to India and conduct research after being trained at Montreal in some cutting-edge areas in neuroscience.

Reference

Abhishek Tiwari, Nancy Ashary, Neha Singh, Shipra Sharma, Deepak Modi, Modulation of E-Cadherin and N-Cadherin by ovarian steroids and embryonic stimuli (2021). Tissue and Cell, Volume 73, 101670.

Edited by: Neha Varshney