Evidence of Increased Oxidative Stress in the Placental Tissue of Women Who Suffered an Episode of Psychosis during Pregnancy

Abstract

Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT–qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients.

Assessment of Tissue Expression of the Oxytocin–Vasopressin Pathway in the Placenta of Women with a First-Episode Psychosis during Pregnancy

“…However, the pathogenic mechanisms connecting FEP with adverse obstetric and neonatal outcomes are poorly understood. Previous studies have found that the placentas of FE-PW show evidence of increased cell death, hypoxia, ferroptosis, and oxidative stress [ 14 , 15 , 16 ], suggesting a possible link between this organ and suffering from FEP during pregnancy. In this work, we have demonstrated abnormal expression of OXT and AVP and their main receptors (OXTR and AVPR1A) in the chorionic villi as well as in the decidual cells of placenta of FEP women during pregnancy, gaining further insights into the pathogenic implications of this condition in the placenta.…”

“…To achieve this, the placenta fulfills pleiotropic functions including maternofetal exchange, endocrine activity, mechanical, chemical, and immunological barrier, and determining maternofetal programming, even beyond gestation [ 13 ]. Our previous research has uncovered different structural changes in the placental tissue of women with FEP, such as increased oxidative stress [ 14 ], increased lipid peroxidation with evidence of ferroptosis [ 15 ], and Tenney–Parker changes related to enhanced hypoxia and apoptosis [ 16 ]. These changes in the structure of the placenta may be a consequence of the psychotic process and could lead to an impairment of fetal neurodevelopment [ 17 ], so its analysis may lead to protective measures of maternofetal wellbeing.…”

Exploring the Role of Mediterranean and Westernized Diets and Their Main Nutrients in the Modulation of Oxidative Stress in the Placenta: A Narrative Review

“…During pregnancy, a set of hemodynamical and cardiovascular changes takes place, increasing the risk of suffering from CVD, especially in the third trimester. Our investigations have revealed increases in oxidative stress and inflammatory markers in the placenta, umbilical cord, and blood of pregnant women with CVD [102][103][104]. Using RT-qPCR and immunohistochemistry, we determined an increase in oxidative stress markers NOX1, NOX2, iNOS, PARP, and ERK in the placental tissue of women with CVD in comparison to healthy pregnant women, as well as malondialdehyde (MDA) plasma levels [104].…”

“…We previously demonstrated significant histopathological changes in the placentas of women who suffered first-episode psychosis (FEP) during pregnancy, such as an increase in the number of placental villi, bridges, syncytial knots, and syncytial knots/villi, as well as hypoxic marker HIF-1α and apoptotic markers BAX and Bcl-2 [107]. Moreover, the gene and protein expressions of oxidative stress markers NOX-1, NOX-2, iNOS, and PARP were found to be upregulated, suggesting a direct link between FEP and oxidative stress in the placenta [103]. In parallel with this fact, we observed an increase in lipid peroxidation (MDA levels) and ferroptosis, a special type of cell death linked with ROS generation and oxidative stress [108].…”

A Review: Integrative Perspectives on the Features and Clinical Management of Psychotic Episodes in Pregnancy

“…On the other hand, the standard treatment of patients with bipolar disorder is based on the use of lithium, which completely crosses the placenta, highlighting how the risk of teratogenicity can be up to double compared to that among healthy controls, mainly those with cardiac conditions, such as Ebstein’s malformation, alterations in the right ventricle, coarctation of the aorta and mitral atresia; in addition to the fact that at birth, the adverse effects of lithium generate apnea, bradycardia and seizures, among other adverse effects [ 24 , 25 , 26 ]. It should be mentioned that in these patients, the treatment of choice is based on the use of first-generation antipsychotics such as haloperidol, with the use of second-generation antipsychotics such as risperidone, quetiapine or olanzapine according to different authors [ 27 , 28 ]. In patients with bipolar disorder who do not respond to previous therapies, lithium could be used according to different guidelines, despite the possible adverse and teratogenic effects described [ 29 ].…”