PARENT SESSION
BIOLOGY OF THE FEMALE REPRODUCTIVE TRACT
Harborside C
7:30 AM-10:00 AM

(558) EVIDENCE FOR ESTROGEN-MEDIATED DOWNREGULATION OF INTEGRIN V3 ON CYCLE DAY 16 IN BOVINE ENDOMETRIUM.

Kimmins, Sarah¹, MacLaren, Leslie¹, ¹ Nova Scotia Agricultural College, Truro, Canada

ABSTRACT- Integrin V3 is present at the fetomaternal interface and participates in cell-extracellular matrix adhesion during embryo attachment. Expression of this integrin is transiently downregulated in subepithelial intercaruncular stroma on day 16 of the estrous cycle, but not in pregnancy. This downregulation coincides with initiation of the luteolytic mechanism which is marked by the appearance of estrogen receptors in the luminal epithelium. The role of estrogen in the regulation of V3 is unclear. In culture acute estrogen exposure decreases V3 in stromal cells, however V3 levels are high at estrus. The objective of this study was to determine the effects of the anti-estrogen, ICI 182 780 (ICI), on V3 expression in day 16 bovine endometrium. Beef heifers were synchronized and from cycle days 14-16 received twice daily uterine infusions of either ICI (6 mg/day, n=3), or saline (n=3, expect no V3 ), or estradiol 17 (234 ng/day, n=3, expect high V3). On day 16 reproductive tracts were dissected, and frozen for cryosectioning and RNA analysis. Northern blots showed that endometrium from control animals had lower levels of 3 than endometrium from treated animals (P<0.05). Little or no V3 protein in intercaruncular subepithelial stroma was detected by immunostaining. In contrast tissue from estrogen treated animals had high levels of 3 mRNA expression that did not differ from ICI treated animals (P>0.10). Cryosections from treated animals showed strong staining for V3 in subepithelial stroma and scores were not different between estrogen and ICI treatments (P>0.10). The antagonist effects of ICI prevented downregulation of V3 on day 16; low levels of estrogen arising from the preovulatory follicle were blocked and suppression of V3 was prevented. We propose that stromal expression of V3 is regulated in a biphasic manner whereby low levels of estrogen repress transcription and high levels stimulate expression. Estrogen treated animals had high levels of V3 in subepithelial stroma. The infusion of estradiol in combination with endogenous estradiol exceeded a threshold that triggers downregulation of V3 on day 16. Whether V3 is sensitive to direct regulation by estrogen, or a feed forward mechanism related to a transient factor specific to the day 16 uterine environment remains unresolved.

KEY WORDS: Integrin, Endometrium, Estrogen, ICI 182 780