Interleukin-1β-stimulated PGE2 production from early first trimester human decidual cells is inhibited by dexamethasone and progesterone

Prasad

Journal of Medical Microbiology

et al. 2016

A study was undertaken to quantify the expression of prostaglandin (PG) receptors and find the effect of gestational age on expression of PG receptor genes in Chlamydia trachomatis-infected recurrent spontaneous aborters (RSA). Endometrial curettage tissue (ECT) was collected from 130 RSA (Group I) and 100 age-matched controls (Group II) at the Department of Obstetrics and Gynecology, Safdarjung Hospital, New Delhi (India). PCR was performed for diagnosis of C. trachomatis cryptic plasmid; mRNA expression of PG receptor genes was assessed by real-time PCR (q-PCR), while serum progesterone/estrogen levels were determined by respective commercial kits. Data were evaluated statistically. A total of 15.4 % RSA (GroupI) were diagnosed as C. trachomatis-positive (200 bp), whereas controls were uninfected. q-PCR showed significant upregulation (P<0.0001) of PGE2 (EP-1, EP-2, EP-3, EP-4), PGF2a (FP) and PGI2 (IP) receptors in Group I versus Group II. The expression of PG receptors increased significantly with advanced gestational age (P<0.002); however, only contractile receptors, EP-1, EP-3 and FP, were positively correlated with gestational age in Group-I. In infected RSA, mean serum progesterone level was significantly low (P<0.0001) while serum oestrogen was high (P<0.0001). Overall, the data suggest that increased expression of PG receptors, particularly contractile gene receptors (EP-1, EP-3, FP), with advanced gestational age and altered steroid levels could be a possible risk factor for abortion in Chlamydia-infected RSA.

Section: Discussionsupporting

confidence: 64%

Expression of prostaglandin receptors in Chlamydia trachomatis-infected recurrent spontaneous aborters

Prasad

Journal of Medical Microbiology

et al. 2016

Journal of Reproduction and Development

“…Studies have shown that inflammatory cytokines increase PGE2 and PGF2α production by gestational tissues [36,37]. In support of these observations, intra-amniotic inoculation of pregnant rhesus monkeys with group B Streptococci increased amniotic fluid cytokine concentrations (TNFα IL-1, β and IL-6) followed by sequential increased production of prostaglandins (PGE2 and PGF2α) prior to increases in uterine contractions [18,36].…”

Section: Discussionsupporting

confidence: 52%

Hormonal Profiles of Late Gestation Ewes Following Intra-uterine Inoculation With and Without Lux-modified Escherichia coli

Moulton

Ryan

Christiansen

et al. 2009

Abstract. The objectives of these investigations were to develop an ovine model for Escherichia coli (E. coli)-induced preterm delivery, and monitor ewe hormonal response. EXP 1: Ewes (105 ± 13 days of gestation) were allotted to the following intra-uterine inoculations: Saline-(CON; n=5); 1 × 10 6 CFU/ml (Low Treatment, LT; n=6); or 1 × 10 7 CFU/ml (High Treatment, HT; n=6) E. coli. Twenty-four h after inoculation, the HT ewes had increased (P<0.05) cortisol compared to LT and CON ewes, and HT and LT ewes had increased (P<0.05) progesterone compared to CON ewes. Preterm delivery was 33% for LT ewes and 0% for HT and CON ewes. EXP 2: Ewes (124 ± 18 days of gestation) were allotted to the following intra-uterine inoculations using lux-modified E. coli: Trial-1: Luria Broth (LB; CT1; n=5); 4.0 × 10 6 CFU (n=5), 20.0 × 10 6 CFU (n=5); and Trial-2: LB (CT2; n=5), 1.2 × 10 6 CFU (n=5), and 5.6 × 10 6 CFU (n=5) E. coli-lux. Preterm delivery occurred between 48 and 120 h post-inoculation in 60, 25, 60 and 75% of ewes infected with 1.2, 4.0, 5.6, and 20 × 10 6 CFU, respectively. Serum cortisol and progesterone did not differ (P>0.05) between CT1 or CT2 and inoculated ewes. In summary, 25 to 75% of ewes inoculated preterm delivered. However, variable results in cortisol and progesterone profiles between Control and inoculated ewes were observed between the two studies. Key words: Cortisol, Escherichia coli, Pregnant, Progesterone, Sheep (J. Reprod. Dev. 55: [55][56][57][58][59][60][61][62] 2009) eproductive efficiency of livestock is reduced in response to non-specific uterine infections and ultimately causes a decline in profit potential of sheep farms. Of the 66,100 sheep operations with a total national flock of 6,965,000 head, 18.3 ± 0.5 percent of ewes in the flocks were culled in 2000. Of the culled ewes 5.5 ± 0.4 percent were due to failure to lamb [1].In dairy cows, uterine infections reduce reproductive efficiency; with infections reported to be associated with changes in progesterone and estrogen concentrations during the estrous cycle [2]. In a retrospective study from 1999 to 2006 on a total of 434 reproductive cases involving dairy farms and beef cow-calf farms in Finland; inflammatory lesions suggesting bacterial infection were detected in 30% (85/286) of fetuses and in 14% (20/148) of stillbirths. Significant bacteriological load was isolated from 26% of fetuses and 10% of stillbirths [3]. In swine, a reduction in ability of the uterus to resist infections occurred with endogenous and exogenous progesterone [4]. Similarly in the ewe, the uterus is rendered resistant to bacterial infection when progesterone levels are low, while the uterus becomes susceptible to post partum infections with progesterone supplementation [5]. In goats, low estrogen levels with low progesterone probably enhanced the uterine immune system post partum [6]. Thus resistance to uterine infections have been reported among livestock when concentrations of progesterone are basal, yet when concentrations of progesterone are increased...

“…C O X -1 i s a constitutive enzyme involved in housekeeping functions, whereas COX-2 is an inducible enzyme that plays a role in va rio u s p hy si ol og ic a l conditions. It has been reported that COX-2 is involved in differentiation of human ESC [18][19][20] and that COX-2 is the main enzyme controlling the synthesis of prostaglandins by human decidual cells [21]. From these findings, there seems to be a possibility that withdrawal of ovarian steroids causes the decrease in Cu,Zn-SOD and the increase in ROS, which in turn induce menstruation by stimulating PGF2α production via COX-2.…”

mentioning

confidence: 73%

Withdrawal of Ovarian Steroids Stimulates Prostaglandin F2.ALPHA. Production Through Nuclear Factor-.KAPPA.B Activation via Oxygen Radicals in Human Endometrial Stromal Cells: Potential Relevance to Menstruation

et al. 2004

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-