PARENT SESSION

(151) STAT1 IS DIFFERENTIALLY REGULATED BY CONCEPTUS ESTROGEN AND PROTEINS IN THE PORCINE UTERUS.

Joyce, Margaret¹, Ross, Jason², Ashworth, Morgan², Geisert, Rodney², Burghardt, Robert¹, Johnson, Greg¹, ¹ Texas A&M University, College Station, TX² Oklahoma State University, Stillwater, OK

ABSTRACT- During the peri-implantation period of pregnancy, several interferon(IFN)-stimulated genes (ISGs) increase in the uteri of primates, rodents, ruminants and pigs. In pigs, most are expressed in the stroma, perhaps in response to conceptus IFNs delta and gamma. However, expression of STAT1 is more complex. Similar to other ISGs, STAT1 increases in stroma only adjacent to conceptus. In contrast, it also increases in the lumenal epithelium (LE) correlating with conceptus secretion of estrogen for pregnancy recognition. Therefore, the objective was to determine if conceptus estrogen and/or proteins regulate STAT1 in porcine endometrium. To evaluate the effect of estrogen, cyclic gilts were treated daily (Days 11-14) with 5 mg estradiol benzoate (i.m.) or vehicle and hysterectomized on Day 15. To examine effects of conceptus proteins, cyclic gilts were treated with steroid as above, implanted on Day 12 with mini-osmotic pumps that continuously delivered control serum proteins (Cx) to one horn and conceptus secretory proteins (CSP) to the other, and were hysterectomized on Day 16. STAT1 mRNA localized to the LE of estrogen-treated, but not control gilts. Intrauterine infusion of CSP increased steady-state levels of STAT1 mRNA compared to Cx infusion (P < 0.05). The difference was due to stromal expression in CSP-treated horns. To further investigate differential regulation of STAT1 by estrogen and CSP, pregnant gilts were treated daily (Days 9-10) with 5 mg estradiol cypionate (i.m.) or vehicle and hysterectomized on Day 10, 12, 13, 15, or 17. This early exposure to estrogen results in embryo loss by Day 15-17. Although total endometrial STAT1 mRNA was 2.1 fold lower in Day 15 estrogen-treated than control pregnant gilts, STAT1 was present in the LE of all animals in the study. In contrast, while STAT1 mRNA increased in stroma of control pregnant gilts, no stromal expression was observed in gilts exposed to early estrogen. These results indicate that inappropriate estrogen leading to progressive conceptus degeneration compromises CSP, which are required for stromal expression of STAT1. The temporal and spatial uterine expression of STAT1 highlights the complex and overlapping events of pregnancy recognition and remodeling for placentation necessary for conceptus survival during early pregnancy.

KEY WORDS: pregnancy, uterus, porcine, stat1