March 8, 2019
Second-year student Justine H. McKee just had an article titled “Rapamycin Corrects T Regulatory Cell Depletion and Improves Embryo Implantation and Live Birth Rates in a Murine Model” published in the journal Reproductive Sciences. The full-text article is available for ACOM faculty, staff, and students. Contact the LRC for details on how to access the full text.
Justine explains more about her research below.
Before starting at ACOM, I had the opportunity of taking part in a research project at the Program of Reproductive and Adult Endocrinology (PRAE) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health. The mission of the PRAE division is to identify critical mechanisms necessary to successful implantation and understanding the pathology behind abnormal pregnancy and implantation in order to create effective and cutting-edge treatment options and protocols for patients with these conditions.
“I was so honored to be a part of this project and to have the opportunity to work with patients undergoing infertility treatments, some of which suffered from unexplained infertility. I’m ecstatic that we are that much closer to finding more effective treatment options for these patients so that we can one day provide them the chance at becoming a mother.”
Our specific project was designed to target future treatments for patients dealing with recurrent pregnancy loss (RPL) and recurrent implantation failures (RIF). Currently, infertility affects approximately 7-15% of all couples in the US, with 10% of those couples experiencing “unexplained infertility.” As it stands, there are very few treatment options for women experiencing unexplained infertility leading to RPL and RIF. Based on previous research, women with unexplained infertility have lower T regulatory T cells when compared to fertile women. T regulatory T cells are a subset of T cells that regulate the immune system to maintain tolerance to self- antigens and prevent autoimmune disease. We used a genetically engineered mouse model that duplicates recurrent embryo implantation failure in humans with smaller litter sizes after being given one injection of diphtheria toxin before mating. The injection of diphtheria toxin causes these mice to deplete T regulatory cell levels and subsequently have smaller litter sizes (from 7 to 4 pups).
In our experiment, we gave these mice Rapamycin to increase their T regulatory cell levels at the time of embryo implantation and found that litter sizes returned back to normal. Rapamycin is an antibiotic and immune modulator that is normally used to prevent solid organ transplant rejection in humans. This medicine has safely been used by women for decades to prevent organ transplant rejection during pregnancy and it may help future women suffering from recurrent embryo implantation failure or unexplained infertility if they also have low T regulatory cells.
Congratulations on the publication of your article, Justine!