Abstract. The present study was undertaken to investigate whether withdrawal of estrogen and progesterone (EP-withdrawal) stimulates prostaglandin F2α (PGF2α) production through oxygen radical (ROS)-induced NF-κB activation in human endometrial stromal cells (ESC). To study the EPwithdrawal, ESC that had been treated with estradiol (E, 10 -8 M) and medroxyprogesterone acetate (MPA, 10 -6 M) for 12 days were then incubated with or without E+MPA for a further 11 days. PGF2α concentrations in the medium and cyclooxygenase-2 (COX-2) mRNA levels were significantly increased after EP-withdrawal, while they were unchanged by the continuous treatment with E+MPA. When ESC were incubated with N-acetyl-L-cysteine (Nac, 50 mM), an antioxidant, during EP-withdrawal, Nac blocked the increases in PGF2α production and COX-2 mRNA expression caused by EPwithdrawal. Next, we examined whether ROS generated in response to EP-withdrawal acted through NF-κB activation. Electrophoretic mobility shift assay revealed that EP-withdrawal caused marked increases in NF-κB DNA binding activity, which was completely suppressed by Nac. Furthermore, when ESC were incubated with MG132 (3 µM), which inhibits NF-κB activation, during EPwithdrawal, MG132 blocked the increases in PGF2α production and COX-2 mRNA expression caused by EP-withdrawal. In conclusion, EP-withdrawal stimulates COX-2 expression and PGF2α production through ROS-induced NF-κB activation, suggesting a possible mechanism for menstruation. Key words: Endometrial stromal cell, Prostaglandin F2α, NF-κB, Superoxide dismutase, Superoxide radical (J. Reprod. Dev. 50: [215][216][217][218][219][220][221][222][223][224][225] 2004) eactive oxygen species (ROS), including superoxide radicals, cause cell damage, whereas superoxide dismutase (SOD) is an enzyme specific to scavenging superoxide radicals and protects cells from oxygen radical cytotoxicity. Oxidative stress and its defense system have been reported to play important roles in the regulation of reproductive function [1][2][3][4][5][6][7]. In the human endometrium, SOD activities decrease and ROS levels increase in the late secretory phase, just before menstruation, suggesting that these changes in SOD and ROS may be involved in endometrial breakdown [8]. Recently, much attention has been focused on the reports that ROS act as second messengers in the regulation of cellular function [9-

The change in Ang expression is closely associated with angiogenesis, blood vessel stabilization, and blood vessel regression during the divergent phases of luteal formation, luteal regression, and luteal rescue by pregnancy.

Invasive cervical carcinoma is thought to arise from cervical intraepithelial neoplasm (CIN). Genetic changes that occur during progression of CIN to cervical carcinoma are poorly understood, although they appear to be directly involved in this process. We used comparative genomic hybridization (CGH) with precise microdissection and degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR) to detect genetic alterations in normal epithelial, CIN, and invasive carcinoma tissues colocalized in tumors from 18 patients with squamous cell carcinoma of the uterine cervix. Gains on chromosome 1 and on 3q and losses on 2q, 3p, 4, 6p, 11q, and 17p were frequent alterations found in CIN and invasive carcinoma lesions. Interestingly, several of these genetic changes were observed in preinvasive carcinoma lesions. The frequency and average number of genetic alterations corresponded directly to the extent to which the cervical carcinoma had progressed. Frequent alterations were found in more than 90% of CIN III lesions. Gains on 3q and losses on 11q were the most prevalent genetic alterations found in association with uterine cervix carcinogenesis. The common regions of alteration were 3q26.1-q28 and 11q23-qter. The majority of tumor samples showed variability in genetic alterations across lesion types within a single specimen.

To clarify if migraine-associated vertigo (MAV) and Meniere's disease (MD) share a common pathophysiology, vestibular-evoked myogenic potentials (VEMP) were measured in 11 patients with MAV, 11 with unilateral MD and eight healthy subjects. As acoustic stimuli, tone bursts (TB; 250, 500, 1000 and 2000 Hz) were presented. In healthy subjects, 500-Hz TB evoked the largest amplitude. To quantify this tendency, 500-1000 VEMP slope was calculated, and 500-1000 VEMP slope was the smallest on the affected side of MD patients. Among the 11 MD patients, five had significantly decreased 500-1000 VEMP asymmetry (shift of the tuning to 1000 Hz). Three of the 11 MAV patients also showed a significantly decreased 500-1000 VEMP slope. This finding suggests that MAV might share a common pathophysiology with MD. In addition to this finding, four of the other eight MAV patients showed prolonged p13 latencies. This suggests that MAV could consist of patients with different lesion sites.

Apoptosis contributes to luteal regression in many species. In the postpartum rat, there are two different types of corpora lutea (CL) in the ovary: CL of pregnancy (CLP) and newly formed CL (NCL). To investigate the regulation of apoptosis in the two different types of CL during luteal regression, apoptosis and caspase-3 activity were examined in the CL obtained on Days 7, 15, and 21 of pregnancy and Days 0, 1, 3, 5, 7, and 9 postpartum. Furthermore, the effect of lactation on apoptosis in the CL was examined in two groups of postpartum rats: lactating rats that nurse more than 10 pups, and nonlactating rats that nurse no pups. Apoptotic cells were detected after Day 21 of pregnancy. In the CLP, remarkable increases in the number of apoptotic cells on Days 5 and 9 postpartum were observed in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the CLP were not consistent with those in number of apoptotic cells. In the NCL, an increase in apoptosis was found only on Day 5 postpartum in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the NCL were consistent with those in number of apoptotic cells. In conclusion, apoptosis is, at least in part, involved in luteal regression after parturition, and lactation appears to inhibit apoptosis. This study also suggests the presence of a caspase-3-independent mechanism for apoptosis in CLP regression in the rat.