Human placental PPAR‐γ and SOX‐2 expression in serologically proved toxoplasmosis

Abstract

To explore PPAR-γ and SOX-2 transcription factors expression in placenta according to maternal anti-Toxoplasma gondii serological profile during pregnancy and pregnancy outcome. The study included 240 placentas, grouped according to IgM and IgG serostatus and then subgrouped according to pregnancy outcome that varied between miscarriages, premature labour, stillbirth and giving birth to CNS anomaly or apparently healthy neonates. Samples were H&E stained and histopathologically scored blindly. PPAR-γ expression was measured by ELISA, while SOX-2-positive nuclei were stained immunohistochemically to be calculated by ImageJ. The mean pathological score was significantly higher in IgM+ve and IgG rising than IgG-ve and persistent low groups. Former groups showed significantly higher PPAR-γ (mean = 258.63, 227.11). However, PPAR-γ was higher in apparently healthy neonate subgroups. SOX-2 was significantly lower in IgM+ve and IgG rising groups (mean = 12.87, 43.13) and associated with obvious fibrosis. SOX-2 lowest count was in CNS anomaly subgroup. PPAR-γ and SOX-2 changes may give clues of how Toxoplasma induces pathogenesis during vertical transmission. Triggering PPAR-γ expression may be a tool to downregulate the inflammatory response and establish a metabolically permissive cellular environment for Toxoplasma persistence. Low SOX-2 is suspected to disturb placental mesenchymal stem cells pluripotency and neuroectoderm development.

Placental histopathology in preterm birth with confirmed maternal infection: A systematic literature review

“…The study characteristics, PTB definition, placental histopathology classification system, range of infective organisms, and sample size are summarized in Table 1 . The majority (56.5%, 13/23) of studies examined the association between bacterial infection and placental histopathology in PTB [ 30 , 31 , 35 – 39 , 41 , 44 , 46 – 49 ], six studies (26%) examined viral infection [ 29 , 32 , 33 , 42 , 45 , 50 ], and four studies (17%) examined studied parasites [ 28 , 34 , 40 , 43 ].…”

“…Of the included studies, 13 were cohort studies, seven were case-control studies and three were sub-analysis of randomised controlled trials. Most included studies (65%, 15/23) were conducted prospectively and 14 mentioned the blinding of the pathologist(s) to clinical data [ 29 – 31 , 34 – 37 , 39 , 40 , 43 – 45 , 47 , 50 ] ( Table 1 ). The gestational age assessment by ultrasound was clearly specified in 12 articles [ 28 , 29 , 31 , 36 , 37 , 39 , 40 , 42 , 43 , 45 , 47 , 50 ].…”

“…investigated an association between a Toxoplasma gondii infection and PTB by using the mean histopathological score based on abnormalities such as fibrin deposition, intervillous haemorrhage, villous degeneration and fibrosis, haemorrhage and nearby inflammatory cellular infiltrate and infarction [ 34 ]. They reported that the highest pathological score was observed in anti-toxoplasma IgM positive cases compared to anti-toxoplasma IgM/IgG negative cases [ 34 ]. No other studies on parasites such as soil transmitted helminths, Schistosomiasis , Trichomonas vaginalis , Giardia , Cryptosporidium were identified for this review.…”

“…Although the association between PTB and placental malaria remains inconclusive, it was significantly associated with other adverse birth outcomes such as SGA and miscarriage [ 28 , 40 , 43 ]. The only other study in the parasitic subgroup was of toxoplasmosis in which placental histopathological findings were more similar to acute and chronic inflammatory changes reported for bacteria, although the authors created their own detailed scoring system [ 34 ].…”

“…Contamination of the placenta and membranes can occur due to PPROM or during passage through the vagina, or skin during Caesarean section, and sequencing methods do not distinguish between viable and non-viable bacteria [ 74 , 75 ]. Some authors in this review indicated that the role of infection in PTB may be underestimated due to limitations in the diagnostic methods [ 31 , 47 , 49 ], the difficulty of distinguishing between colonisation and contamination [ 35 ], and decreased bacterial abundance due to antibiotic treatment prior to tissue sampling [ 32 , 34 , 35 ]. No manuscript in this review reached the ideal “gold standard” to link the pathogen and placental histopathology of “amniotic fluid culture/polymerase chain reaction (PCR) and placental pathology” [ 70 ].…”