Apoptosis caused by an inhibitor of NO production in the decidua of rat from mid-gestation

Abstract

We previously reported that nitric oxide (NO) is first detected in the uterus of a pregnant rat on gestational day 13.5 (GD13.5) and that NO levels peak on GD17.5. In addition, NO production in the uterus is mainly derived from the decidua and not the myometrium. The aim of the present study was to reveal the role of NO that peaked on GD17.5 of gestation in the decidua. To inhibit NO production, pregnant rats were continuously administered by an nitric oxide synthase inhibitor, N(G)-nitro-L-arginine-methyl ester (L-NAME) for 48 h. In the control group, saline was infused instead of L-NAME. After treatment, the decidua were obtained from GD13.5, GD17.5 and GD21.5 rats. Apoptosis and activated caspase-3-positive cells were observed by transferase-mediated dUTP nick-end labeling (TUNEL) assay and immunohistochemistry, respectively. The caspase-3 enzyme activity was also measured in the cell lysate from the decidua. The numbers of TUNEL-positive cells and activated caspase-3-positive cells each increased and the amount of caspase-3 activity also increased significantly in rats on GD17.5 than in rats in the control group, but no changes were observed in rats on GD13.5 and GD21.5. Furthermore, enzyme activity regarding the initiator caspases, caspase-8 and -9, upstream factors for caspase-3 in the caspase cascade, was measured simultaneously on GD17.5 under the same treatment. Caspase-8 and -9 enzyme activities increased significantly in the control group; an increment of caspase-8 activity was especially prominent. The present results indicate that an inhibitor of NO production caused apoptosis through typical apoptotic signals in the decidua on GD17.5, suggesting that an NO peak in the decidua is essential to cell survival and the maintenance of uterine formation.

The anandamide effect on NO/cGMP pathway in human platelets

“…For instance it may be one of the factors required for platelet survival and the elevation of endogenous NO can play an important role in these mechanisms, as NO can be considered a central effector in the regulation of both cell survival and apoptosis [Choi et al, 2002]. A key role of NO bioavailability in fatal arterial hypertension [Hu et al, 2010], in gestation [Suzuki et al, 2010], in liver fibrosis resolution [Mòdol et al, 2011], and in the regulation of erythrocytes survival was recently demonstrated [Nicolay et al, 2008; Chowdhury et al, 2010]. Varying kinases (PKA, AKT, calmodulin‐dependent kinase II or AMP‐activated protein kinase), dependent on the stimuli applied, appear to be involved in eNOS phosphorylation and activation.…”

Roles of Nitric Oxide and Asymmetric Dimethylarginine in Pregnancy and Fetal Programming

“…Consistent with these findings, increased vasoconstriction of human stem villous feto-placental arteries [47] and increased ovine umbilical vascular resistance [48] are caused by an NOS inhibitor, N G -monomethyl- l -arginine. Suzuki et al showed that N G -nitro- l -argininemethyl ester, an NOS inhibitor, caused apoptosis in the decidua, suggesting that NO in the decidua is essential to cell survival and the maintenance of uterine formation [49]. …”

Environmental Factors in the First Trimester and Risk of Oral-Facial Clefts in the Offspring

“…In the literature, ambient air pollutants have been associated with adverse obstetric outcome such as low birth weight, 21,22 intrauterine growth restriction, [23][24][25] preterm delivery, [25][26][27] and certain congenital anomalies such as the increase in mainly cardiovascular anomalies with exposure to elevated carbon monoxide (CO), O 3 , particulate matter <10 mmol/L (PM 10 ), and SO 2 levels. [28][29][30][31] For nonsyndromal oral-facial clefts, this relationship remains unclear, as it was reported to increase with increasing proximity to the municipal solid waste incinerator, 32 to have no relationship with traffic exposure 32 as well as being linked to outdoor O 3 . 33 Taken together, the most likely reason for the conflicting literature and the largely futile attempts in elucidating the underlying aetiological mechanisms for the formation of isolated oral-facial clefts is the permutation of and possibly sequential interactions in these factors that result in the ultimate occurrence of oral-facial clefts as well as the likelihood that isolated CL and isolated CP have different aetiologies.…”

“…37 Moreover, in an animal study, NO was found to peak in the decidua and thought to be essential for the maintenance of the cell survival. 30 The NO is also involved in the adjustment of the proper timing of blastocyst implantation and supporting fetal growth. 38 As well, it is protective against infection, but by the same token it can damage tissues, proteins, and DNA.…”