Neurobehavioral effects of maternal triphenyl phosphite exposure: A comparative experimental study using the valproic acid model

Petek Bilim; Kübra Çelik; Gurur Garip; Ahmet Giray Yardımcı; Buket Şura Yardımcı; Meral Baka

doi:10.19161/etd.1686034

TR EN

Maternal trı̇fenı̇l fosfı̇t maruzı̇yetı̇nı̇n nörodavranışsal etkı̇lerı̇: valproı̇k ası̇t modelı̇ ile karşılaştırmalı deneysel bir çalışma

Öz

Amaç: Nörogelişimsel bozukluklar, embriyonik dönemde ortaya çıkan ve yaşam boyunca devam eden bir veya daha fazla gelişimsel alandaki bozukluklarla karakterize edilmektedir. Nörogelişimsel bozukluklardan biri olan otizm, hayvan modellerinde valproik asit (VPA) ile indüklenebilmektedir. Bu çalışma, nörotoksik bir organofosfor bileşiği olan trifenil fosfit (TPP) ve VPA'ya maternal maruziyetin sonuçlarını nörodavranışsal değişiklikler açısından karşılaştırmak amacıyla planlanmıştır. Gereç ve Yöntem: Gebe sıçanlar randomize şekilde üç gruba ayrılmıştır: VPA (n=3), TPP (n=3) ve kontrol (n=3). Her gruba embriyonik 12.5. günde intraperitoneal VPA, TPP veya salin (kontrol grubu için) enjeksiyonu yapılmıştır. Erkek yavrular (grup başına n=10) doğum sonrası 33-34. günlerde Üç Odacıklı Sosyal Etkileşim Testi ve Mermer Gömme Testi kullanılarak değerlendirilmiştir. Hayvanlar immünohistokimyasal (IHC) analiz için postnatal 35. günde perfüze edilmiştir. Bulgular: Üç Odacıklı Sosyal Etkileşim Testi sonuçları; VPA ve TPP gruplarında kontrol grubuna kıyasla sosyal etkileşimde anlamlı bozulmalar olduğunu göstermiştir (p<0.05). Ayrıca, TPP grubunda bilye gömme davranışında anlamlı bir artış saptanmıştır (p<0.05). Histolojik analizler ile kontrol grubunun subgranüler zonunda (SGZ) VPA ve TPP gruplarına göre daha yüksek nestin-pozitif hücre yoğunluğu tespit edilmiştir (p<0.05). Connexin-43 ekspresyonunda, TPP grubunun CA1 bölgesinde kontrol grubuna kıyasla artış bulunmuş (p<0.05) ancak VPA grubunda ise anlamlı bir değişiklik olmamıştır. Sinaptofizin (SYN) ise CA3 bölgesinde kontrol grubunda, VPA ve TPP gruplarına kıyasla daha yüksek eksprese edilmiştir (p<0.05). Sonuç: Araştırmanın bulguları, TPP'nin maternal maruziyetinde yavruların nörogelişimsel bozukluklar açısından özellikle otizm için riskli olarak değerlendirilebileceğini ortaya koymuştur.

Anahtar Kelimeler

Neurobehavioral effects of maternal triphenyl phosphite exposure: A comparative experimental study using the valproic acid model

Abstract

Aim: Neurodevelopmental disorders are characterized by impairments in one or more developmental domains originating in the embryonic period and persisting throughout life. Autism, experimentally induced by valproic acid (VPA) in animal models, is a neurodevelopmental disorder. This study aimed to compare the outcomes of maternal exposure to triphenyl phosphite (TPP), a neurotoxic organophosphorus compound, and VPA in terms of neurobehavioral alterations. Materials and Methods: Pregnant rats were randomly assigned to three groups: VPA (n=3), TPP (n=3), and control (n=3). Each group received an intraperitoneal injection of either VPA, TPP, or saline (for the control group) on embryonic day 12.5. Male offspring (n=10 per group) were evaluated on postnatal days 33–34 using the Marble Burying Test and the Three-Chambered Social Interaction Test. Animals were perfused on postnatal day 35 for immunohistochemical (IHC) analysis. Results: TPP group exhibited a significant increase in marble burying behavior (p<0.05). Also, Three-Chamber Social Interaction Test revealed significant impairments in social interaction in the VPA and TPP groups compared to the control (p<0.05). Histologic evaluation revealed higher nestin-positive cell density in the subgranular zone of the control group compared to VPA and TPP groups (p<0.05). Synaptophysin expression in the CA3 region was higher in the control group than in the VPA and TPP groups (p<0.05). Connexin-43 expression increased in the CA1 region of the TPP group compared to controls (p<0.05), while no significant change was observed in the VPA group. Conclusion: Maternal TPP exposure may be regarded as a risk factor for autism-related neurodevelopmental disorders.

Keywords

Destekleyen Kurum

This work was supported by the Scientific Research Project Coordination of Ege University, İzmir, TURKEY

Proje Numarası

18-SBE-003

Etik Beyan

Approval of the experimental protocol was granted by the Local Ethics Committee for Animal Experiments affiliated with Ege University (Approval No: 2017-081).

Teşekkür

The authors gratefully acknowledge the support provided by the Scientific Research Projects Coordination Unit (BAP) of Ege University, İzmir, Turkey.

Kaynakça

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Ayrıntılar

Birincil Dil

İngilizce

Konular

Hücresel Sinir Sistemi , Merkezi Sinir Sistemi , Sinirbilim (Diğer)

Bölüm

Araştırma Makalesi

Yazarlar

Petek Bilim ^*
0000-0003-2043-6699
Türkiye

Kübra Çelik
0000-0002-0161-6179
Türkiye

Gurur Garip
0000-0002-2999-477X
Türkiye

Ahmet Giray Yardımcı
0000-0003-0337-1803
Türkiye

Buket Şura Yardımcı
0000-0003-0184-3774
Türkiye

Meral Baka
0000-0003-0497-5254
Türkiye

Yayımlanma Tarihi

10 Haziran 2025

Gönderilme Tarihi

28 Nisan 2025

Kabul Tarihi

14 Mayıs 2025

Yayımlandığı Sayı

Yıl 2025 Cilt: 64 Sayı: 2

DOI

https://doi.org/10.19161/etd.1686034

IZ

https://izlik.org/JA78TG87YD

Kaynak Göster

RIS / Bibtex

Vancouver

1.Petek Bilim, Kübra Çelik, Gurur Garip, Ahmet Giray Yardımcı, Buket Şura Yardımcı, Meral Baka. Neurobehavioral effects of maternal triphenyl phosphite exposure: A comparative experimental study using the valproic acid model. ETD. 01 Haziran 2025;64(2):381-9. doi:10.19161/etd.1686034