PARENT SESSION
Implantation & Early Development

THE DEFECT IN CONCEPTUS ELONGATION IN UTERINE GLAND KNOCKOUT (UGKO) EWES IS DUE TO AN ABSENCE OF ENDOMETRIAL GLANDS, BUT NOT DIFFERENCES IN EXPRESSION OF LUMENAL EPITHELIAL ADHESION MOLECULES .

Gray, C. Allison¹, Johnson, Greg¹, Burghardt, Robert², Bazer, Fuller¹, Spencer, Thomas¹, ^{1 2}

ABSTRACT- Endometrial glands synthesize, secrete and/or transport substances hypothesized to be necessary for conceptus (embryo/fetus and placental membranes) survival and growth. Exposure of neonatal ewes to a 19-norprogestin epigenetically ablates endometrial gland morphogenesis and results in an adult uterine gland knockout (UGKO) phenotype. Normal conceptuses can be obtained in uterine flushes of UGKO ewes on Days 6 and 9 post-mating, but not on Day 14. This study evaluated endometrial integrin and mucin glycoprotein (MUC)-1 expression in Day 14 bred UGKO, normal cyclic or bred ewes. UGKO ewes (n=11) were synchronized to estrus (Day 0) and bred to fertile rams; control ewes were bred at estrus to either vasectomized (n=4) or fertile rams (n=8). On Day 14 post-mating, uteri were flushed with saline, ewes were hysterectomized, and uterine sections were frozen for cryosectioning. Uterine flushes from bred control ewes contained filamentous conceptuses (n=6), whereas UGKO uterine flushes contained either no conceptus (n=4), a growth-retarded, tubular conceptus (n=6), or a fragile, filamentous conceptus (n=1). Frozen uterine cross-sections were evaluated by immunofluorescence for expression of integrins v, 5, 3, 5, and heterodimer 91, and glycoprotein MUC-1. MUC-1 and all integrins, except 91, were expressed at the apical surface of the endometrial lumenal epithelium (LE) with no differences in expression between bred UGKO, cyclic or bred control ewes. These results complement recent studies finding no differences in LE expression of several epithelial-specific genes between normal and UGKO ewes on Day 9 post-mating. Available results support the hypothesis that defects in peri-implantation conceptus survival and growth in UGKO ewes are not due to alterations in maternal expression of adhesion molecules, but are due to an absence of endometrial glands and their secretions. Genomic and proteomic strategies should be useful to identify gland-specific genes that regulate conceptus development and determine the functional and embryotrophic capacities of the adult uterus. Supported by USDA Grant 98-35203-6322 to TES.

KEY WORDS: ovine, endometrium, glandular epithelium, implantation