Awarded Project: "Estrogen reverses progestin-mediated increases in susceptibility to genital virus pathogens"

Estrogen reverses progestin-mediated increases in susceptibility to genital virus pathogens 

Dr. Christopher J. Miller, in conjunction with Stanford University, received a five year grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH.  Prior work from our research group revealed that while depot-medroxyprogesterone acetate (DMPA) and other progestins used for contraception compromise genital mucosal barrier function, treatment of humanized mice with DMPA and estrogen (E) restores barrier integrity and blocks genital HIV transmission. These results identify unforeseen advantage of hormonal contraceptive strategies that use progestin and E (i.e., they avoid weakening of genital mucosal barrier protection caused by progestins alone). In this proposal, we will acquire essential information related to this approach by: 1) using mouse models to define E-mediated mechanisms that boost genital mucosal barrier function; 2) confirm mouse data in rhesus macaques (RM) administered DMPA and an E-releasing intravaginal ring (E-IVR); and 3) show  genital SIV transmission is blocked in RM administered DMPA and E-IVR prior to infection.