Molecular characterization of physis tissue and hormonal profiles of female rats neonatally exposed to low-dose bisphenol A
Molecular characterization of physis tissue and hormonal profiles of female rats neonatally exposed to low-dose bisphenol A
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DOI：
10.1177/07482337231156666
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发表时间：
2023-02
影响因子：
1.9
通讯作者：
Chenyan Jiang;Guanglin Gao;Wen-yao Sun;Yan-yan Sun;Jian Yu
中科院分区：
文献类型：
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作者：
Chenyan Jiang;Guanglin Gao;Wen-yao Sun;Yan-yan Sun;Jian Yu
生长板是一种复杂的软骨结构，对纵向骨生长至关重要。作为一种内分泌干扰物，双酚A(BPA)可以通过破坏复杂的营养、细胞、旁分泌和内分泌因子网络来干扰生长板，从而影响骨的纵向生长，导致不同的生长结果。然而，这些现象背后的确切机制仍不清楚。因此，了解新生儿暴露于低剂量双酚A后生长板的分子通路可能有助于确定治疗的研究靶点，这可能有助于调节生长板关闭的过程。在本研究中，雌性SD大鼠从出生后第1天至第15天皮下注射双酚A和玉米油载体(−−1)0.0 5 mg·kg-1·d-1。对从生长板中分离的mRNA进行下一代RNA测序。在PND30上测定骨钙素(OC)、生长激素(GH)和胰岛素样生长因子-1(IGF-1)水平(BPA0.05 mg与赋形剂比较；每组n=5)。我们观察到，与载体组织相比，BPA0.05 mg组织中的基因集在统计学上显著丰富。对差异表达基因(DGs)的进一步分析确定了BPA0.05 mg分泌蛋白(LEP、NPY、AGT、ACE2、C4b和C4BPA)以及局部基质和蛋白酶蛋白(FBN2、LAMC2、ADAMTS16和ADAMTS19)的特异性网络。此外，BPA暴露对OC和GH水平也有影响。我们的结果揭示了双酚A污染植物种的分子特征，可能为植物种成熟、工业品和职业暴露的监管提供新的线索。
Physis is a complex cartilaginous structure that is critical for longitudinal bone growth. As one of the endocrine-disrupting chemicals, bisphenol A (BPA) can interfere with the physis by deranging the complex networks of nutritional, cellular, paracrine, and endocrine factors, and this affects longitudinal bone growth, leading to different growth outcomes. However, the exact mechanisms underlying these phenomena remain unclear. Therefore, understanding the molecular pathways involved in the physis after neonatal exposure to low-dose BPA may permit the identification of research targets for therapeutics, which may aid in modulating the process of growth plate closure. In the present study, female Sprague–Dawley rats were exposed to 0.05 mg·kg−1·day−1 of BPA and corn oil vehicle from postnatal day 1 (PND1) to 15 via subcutaneous injection. Next-generation RNA sequencing was performed for the mRNA isolated from the physis. The levels of osteocalcin (OC), growth hormone (GH), and insulin-like growth factor 1 (IGF-1) were measured on PND30 (BPA0.05mg vs. Vehicle; n = 5 for each group). We observed statistically significant enrichment of gene sets in the BPA0.05mg tissues compared with the Vehicle tissues. Further analysis of the differentially expressed genes (DEGs) identified BPA0.05mg-specific networks of secreted proteins (LEP, NPY, AGT, ACE2, C4B, and C4BPA) as well as those of local matrix and protease proteins (FBN2, LAMC2, ADAMTS16, and ADAMTS19). Furthermore, the levels of OC and GH were affected by BPA exposure. Our results revealed the specific molecular characteristics of physis contaminated with BPA and may provide new clues for physis maturation and supervision of industrial products and occupational exposure.