ESTROGEN AND PROGESTERONE RECEPTORS, CELL-PROLIFERATION, AND C-FOS EXPRESSION IN THE OVINE UTERUS DURING EARLY-PREGNANCY

To evaluate uterine growth during early pregnancy and the potential ro les of estrogen and progesterone in regulating uterine cell proliferat ion and c-fos expression, ewes were assigned randomly to slaughter on day 12 after estrus (nonpregnant, NP), and on days 12, 18, 24, or 30 a fter mating (pregnant, P) in Exp 1 (n = 7 ewes/day) and on days 12 or 14 after estrus and on days 12, 14, 16, 18, 21, or 24 after mating in Exp 2 (n = 3-6 ewes/day). In Exp 1, endometrial expression of c-fos mR NA was evaluated, and labeling index was determined both in vitro (inc orporation of H-3-thymidine) and in vivo (iv injection of bromodeoxyur idine [BrdU], a thymidine analog). Endometrial expression of the c-fos proto-oncogene was increased by approximately 10-fold on days 18, 24, and 30 P compared with day 12 NP or P. Labeling index (proportion of cells incorporating H-3-thymidine or BrdU, which provides an index of the rate of cell proliferation) of endometrial caruncular and intercar uncular tissues was low for day 12 NP or P, increased on day 18 P, and remained elevated on days 24 P and 30 P. On day 18 P, labeling index also was greater for gravid than nongravid horns for both caruncular a nd intercaruncular tissues. In Exp 2, estrogen receptors (ER), progest erone receptors (PR), and proliferating (BrdU-positive) cells were imm unolocalized. The percentage of cells exhibiting specific staining for ER, PR, and BrdU was quantified morphometrically for epithelial, stro mal, and glandular tissues within luminal and deep regions, as well as for myometrial tissues. For luminal epithelium and glands, the rate o f cell proliferation increased dramatically by day 18 P, even though E R and PR levels were low in these compartments. Conversely, the rate o f cell proliferation remained low throughout early pregnancy in deep g lands, deep stroma, and myometrium, in association with sustained or t ransient increases in ER and PR levels. For luminal stroma, the rate o f cell proliferation increased by day 21 P even though ER levels were low and PR levels remained high. Thus, during early pregnancy, c-fos e xpression increased concomitantly with increased endometrial cell prol iferation. In addition, during early pregnancy, ER and PR levels were inversely related to the rate of cell proliferation in most of the ute rine tissue compartments except luminal stroma, which exhibited increa sed cell proliferation even though ER levels were low and PR levels re mained high.