Abstract: 579

A CRITICAL PERIOD OF PROGESTERONE WITHDRAWAL EXISTS FOR ENDOMETRIAL MMPS AND MENSTRUATION IN MACAQUES.

Ov Slayden^{1 *}, Kunie Mah¹ , Robert M Brenner^{1 *}
Division of Reproductive Sciences, Oregon Regional Primate Research Ctr. Beaverton OR. ¹

At the end of the menstrual cycle, progesterone (P) withdrawal induces endometrial matrix metalloproteinases (MMPs) and menstruation. To examine P withdrawal temporal events, we treated 23 spayed pigtailed macaques with estradiol and P to induce artificial menstrual cycles. After one cycle, the P implants were removed and either a blank (control) or a P implant was replaced at 12, 24, 36, 48, 60, or 72 hours (h) after P withdrawal. Menses occurred in controls 72h after P withdrawal. P replacement at 12 and 24h blocked menses completely (n=7), replacement at 36h blocked menses in 3 out of 4 animals, and replacement at 48, 60 and 72h failed to block menses(n=12). The 36h period after P withdrawal is therefore a critical period for menses induction. To evaluate control of MMPs during and after the critical period, P was withdrawn at time 0 and replaced 12, 24, or 48h later. Uteri from control and P-replaced animals were collected 36, 48 and 72h after P withdrawal (n=3/interval). Strong immunocytochemical staining for MMP1 and MMP2 was evident in controls at 36, 48 and 72h. P replacement during the critical period, which blocked menses, blocked expression of both MMPs. This confirms a role for both MMP1 and MMP2 in the initiation of menses. However, P replacement after the critical period, which failed to suppress menses, suppressed MMP1 but not MMP2. Therefore MMP1 may be more important for initiating menses than for sustaining menstrual breakdown, and MMP2 may be more important than MMP1 in sustaining the menstrual breakdown process. We conclude that a critical period of P withdrawal is essential for menstrual breakdown and that during and after this period, different MMPs vary in both their sensitivity to P suppression and their role in menses.

    This abstract is being presented on Tuesday, August 3 at 4:45 PM at Todd 130.