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围产期同时接触毒死蜱和高脂饮食对 kisspeptin 和 GnRHR 的存在及生殖器官的影响

Impact of Perinatal Coexposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs.

作者信息

Lahimer Marwa, Djekkoun Narimane, Tricotteaux-Zarqaoui Sophian, Corona Aurélie, Lafosse Isabelle, Ali Habib Ben, Ajina Mounir, Bach Véronique, Benkhalifa Moncef, Khorsi-Cauet Hafida

机构信息

PERITOX-(UMR-I 01), UPJV/INERIS, UPJV, CURS, Chemin du Thil, 80025 Amiens, France.

ART and Reproductive Biology Laboratory, University Hospital and School of Medicine, CHU Sud, 80025 Amiens, France.

出版信息

Toxics. 2023 Sep 19;11(9):789. doi: 10.3390/toxics11090789.

DOI:10.3390/toxics11090789
PMID:37755799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10534599/
Abstract

Emerging evidence has indicated the involvement of extrahypothalamic Kisspeptin and GnRHR in reproductive function. In this study, we evaluate if maternal exposure to the pesticide chlorpyrifos (CPF) and/or a high-fat diet (HFD) has an impact on the expression of Kisspeptin and GnRHR in the reproductive organs of rats' offspring. A total of 16 pregnant rats are divided into four groups: a control group ( = 4), CPF group (4 rats exposed daily to 1/mg/kg/day), HFD group (4 rats randomly fed a 5.25 kcal/g HFD), and coexposed group (4 rats exposed to CPF and HDF). At postnatal development postnatal day (PND) 60, male and female offspring were sacrificed. The reproductive organs (ovary and testis) were removed, and histological and immunohistological analysis and in silico quantification (TissueGnostics software 6.0.1.102, TissueFAXS, HistoQuest) were applied to investigate the impact of different treatments on Kisspeptin and GnRHR expression in reproductive organs. The main outcomes of the study showed a significant decrease in rat offspring's body weight in the CPF group from PND30 and PND60 ( < 0.05 and < 0.01, respectively). Histological analysis showed a significant increase in the atretic follicle and abnormal testis structure with germ cell desquamation in the CPF-exposed group. The immunodetection quantification of protein shows a significant decrease in GnRHR and Kisspeptin in the HFD and CPF exposed groups, respectively, in testis rat offspring. Perinatal exposure to CPF and HFD exposure affect the reproduction function of rat offspring.

摘要

新出现的证据表明，下丘脑外的 kisspeptin 和促性腺激素释放激素受体（GnRHR）参与生殖功能。在本研究中，我们评估母体暴露于农药毒死蜱（CPF）和/或高脂饮食（HFD）是否会对大鼠后代生殖器官中 kisspeptin 和 GnRHR 的表达产生影响。总共 16 只怀孕大鼠被分为四组：对照组（n = 4）、CPF 组（4 只大鼠每天暴露于 1mg/kg/天）、HFD 组（4 只大鼠随机喂食 5.25kcal/g 的高脂饮食）和共同暴露组（4 只大鼠同时暴露于 CPF 和 HFD）。在出生后第 60 天（PND60），对雄性和雌性后代实施安乐死。取出生殖器官（卵巢和睾丸），应用组织学和免疫组织学分析以及计算机定量分析（TissueGnostics 软件 6.0.1.102、TissueFAXS、HistoQuest）来研究不同处理对生殖器官中 kisspeptin 和 GnRHR 表达的影响。该研究的主要结果显示，CPF 组大鼠后代的体重从出生后第 30 天到第 60 天显著下降（分别为 P < 0.05 和 P < 0.01）。组织学分析显示，CPF 暴露组的闭锁卵泡显著增加，睾丸结构异常，伴有生殖细胞脱落。蛋白质的免疫检测定量显示，在大鼠睾丸后代中，HFD 组和 CPF 暴露组的 GnRHR 和 kisspeptin 分别显著降低。围产期暴露于 CPF 和 HFD 会影响大鼠后代的生殖功能。

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