Xodo Serena, Londero Ambrogio P, Orsaria Maria, Marzinotto Stefania, Colussi Gianluca, Cagnacci Angelo, Mariuzzi Laura, Gri Giorgia
Clinic of Obstetrics and Gynecology, "Azienda Sanitaria Universitaria Integrata di Udine", DAME, University of Udine, 33100 Udine, Italy.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health, University of Genoa, 16132 Genova, Italy.
Life (Basel). 2023 Oct 26;13(11):2122. doi: 10.3390/life13112122.
Severe maternal and newborn morbidity and mortality associated with pre-eclampsia, which are caused partly by premature delivery, affect a factual proportion of pregnancies. Despite its prevalence, the underlying causes of pre-eclampsia remain elusive, with emerging evidence implicating the aryl hydrocarbon receptor (AhR) in its pathogenesis. This study sought to elucidate the involvement of the AhR and its associated pathway in pre-eclampsia by comparing placental components of the AhR pathway in pregnant individuals with and without pre-eclampsia. This case-control investigation was conducted at the University Hospital of Udine from May 2021 to February 2023. The AhR was assessed using immunohistochemistry and immunofluorescence, and its mRNA was evaluated using a Real-Time Quantitative Reverse Transcription PCR. Levels of mRNA expression were also estimated for other components of the AhR pathway (CYP1B1, IDO1, ARNT, TIPARP, S100A4, and AHRR). Our findings show decreased levels of expression of AhR, IDO1, ARNT, TiPARP, and S100A4 in the placental tissues of individuals with pre-eclampsia compared to controls ( < 0.05). The AhR exhibited a distinct localization within the syncytiotrophoblast (nuclei and cytoplasm) and CD45-positive cells (nuclei and cytoplasm). Furthermore, a significant positive correlation between the AhR and S100A4 (rho = 0.81) was observed in normal placentas, while CYP1B1 displayed a significant negative correlation with the AhR (rho = -0.72), within addition to its negative correlation with TiPARP (rho = -0.83). This study illuminates pre-eclampsia's molecular aberrations, suggesting new diagnostic, therapeutic, and mechanistic approaches. This study emphasizes the need for more research to validate and broaden these findings to improve the management of this complex pregnancy condition.
与先兆子痫相关的严重孕产妇和新生儿发病率及死亡率，部分由早产引起，影响了一定比例的妊娠。尽管先兆子痫很常见，但其潜在病因仍不清楚，新出现的证据表明芳烃受体（AhR）参与了其发病机制。本研究旨在通过比较有和没有先兆子痫的孕妇胎盘组织中AhR通路的成分，阐明AhR及其相关通路在先兆子痫中的作用。这项病例对照研究于2021年5月至2023年2月在乌迪内大学医院进行。使用免疫组织化学和免疫荧光评估AhR，并使用实时定量逆转录PCR评估其mRNA。还估计了AhR通路其他成分（CYP1B1、IDO1、ARNT、TIPARP、S100A4和AHRR）的mRNA表达水平。我们的研究结果表明，与对照组相比，先兆子痫患者胎盘组织中AhR、IDO1、ARNT、TiPARP和S100A4的表达水平降低（<0.05）。AhR在合体滋养层（细胞核和细胞质）和CD45阳性细胞（细胞核和细胞质）中表现出独特的定位。此外，在正常胎盘中观察到AhR与S100A4之间存在显著正相关（rho = 0.81），而CYP1B1与AhR之间存在显著负相关（rho = -0.72），此外它与TiPARP也存在负相关（rho = -0.83）。本研究揭示了先兆子痫的分子异常，提出了新的诊断、治疗和机制方法。本研究强调需要更多研究来验证和扩展这些发现，以改善对这种复杂妊娠状况的管理。
