Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall.
OBJECTIVE
Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model.


METHODS
Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43).


RESULTS
MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium.


CONCLUSIONS
Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury.
1Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, Dallas, TX 2Department of Internal Medicine and Pathology, Dallas, TX 3Department of Plastic Surgery, University of Texas Southwestern Medical Center Dallas, TX.
Christopher M
CM
Ripperda
Pedro Antonio
PA
Maldonado
Jesus F
JF
Acevedo
Patrick W
PW
Keller
Yucel
Y
Akgul
John M
JM
Shelton
Ruth Ann
RA
Word
D000282:Administration, Intravaginal; D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D008593:Menopause; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D000072836:Surgical Wound / Q000188:drug therapy* / Q000209:etiology; D014621:Vagina / Q000187:drug effects* / Q000293:injuries / Q000601:surgery; D014945:Wound Healing
D004967:Estrogens