PARENT SESSION

(148) TEMPORAL REGULATION OF ENDOMETRIAL GENES DURING INADEQUATE SECRETORY PHASES IN THE RHESUS MONKEY.

Okulicz, William¹, Ace, Christopher¹, Franz, Charlene¹, ¹ UMass Medical School, Worcester, MA

ABSTRACT- The differential regulation of genes and their products is expected to play an important role in primate endometrial maturation that leads to a temporally restricted window of receptivity. We have previously identified several endometrial genes whose elevated expression was limited to this period (days 17-23 of an adequate cycle) in the rhesus monkey i.e. secretory leucocyte protease inhibitor (SLPI), whey acidic protein four-disulfide core domain 2 (WFDC2), syncytin, and HLA-B associated transcript 2 (BAT2). The objective of the present study was to analyze the expression of these genes during inadequate secretory phases (low serum progesterone (P), cannot support implantation). Simulated inadequate cycles were created in ovariectomized rhesus monkeys by appropriate temporal insertion and removal of silastic implants containing either estradiol or P as in adequate cycles except that a single small P implant was used to achieve secretory phase serum P levels typical of such cycles. RNA was prepared from endometrial tissue (n=3) harvested on days 17-23 of inadequate cycles and converted to temporal cDNA populations. None of the above 4 gene products showed elevated temporal expression between days 13-26 during inadequate cycles. Indeed, secretory leucocyte protease inhibitor (SLPI), WFDC2, syncytin, and BAT2 were decreased in inadequate cycles by 2.8, 4.8, 2.3, and 3.0-fold respectively compared to adequate cycles (day 23). Using laser capture microdissection (LCM), we also compared the endometrial cell-type and regional expression during adequate cycles. SLPI and BAT2 showed an increased expression primarily in the stromal compartment of the functionalis whereas WFDC2 displayed elevated expression in both stroma and epithelia of the functionalis compared to the basalis. No detectable differences for syncytin were observed with these LCM samples. These studies demonstrate a differential expression of several known genes during the window of receptivity that appears to be primarily localized in the functionalis of the primate endometrium, a primary target for blastocyst invasion. Further studies are needed to analyze the molecular and cellular actions of these gene products during this critical period for potential implantation. Supported by HD-31620 from the NICHD (WCO).

KEY WORDS: endometrium, gene expression, secretory phase, rhesus monkey