Disruptions in the hypothalamic-pituitary-gonadal axis in rat offspring following prenatal maternal exposure to lipopolysaccharide
Disruptions in the hypothalamic-pituitary-gonadal axis in rat offspring following prenatal maternal exposure to lipopolysaccharide
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DOI：
10.3109/10253890.2016.1149695
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发表时间：
2016-03-01
影响因子：
2.3
通讯作者：
Zakharova, Lyudmila A.
中科院分区：
文献类型：
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作者：
Izvolskaia, Marina S.;Tillet, Yves;Zakharova, Lyudmila A.
出生后用细菌内毒素脂多糖（LPS）处理改变了大鼠下丘脑-垂体-性腺（HPG）轴的活性和促性腺激素释放激素（GnRH）峰。在发育的关键时期暴露于免疫挑战对应激反应、免疫、代谢和生殖功能具有深远而持久的影响。产前LPS治疗延迟了GnRH神经元的迁移，这与母体和胎儿隔室中细胞因子释放增加有关。我们研究了单次母体暴露于LPS（18 g/kg，i. p.）妊娠第12天（胚胎（E）第12天）对大鼠后代生殖参数的影响。用RIA和ELISA法测定了出生后不同发育阶段雌雄仔鼠下丘脑GnRH含量、血浆促黄体生成素（LH）、睾酮和雌二醇浓度（每组n=10）。记录雌性动物的体重和阴道开放日（VO）。与对照组相比，产前暴露LPS的子代，雌雄仔鼠在P5和P30体重均下降，雌性仔鼠VO延迟，雌雄仔鼠在生后30-60天（P30-P60）下丘脑GnRH含量均下降，雌性仔鼠在P14-P60血浆LH浓度下降，雌性仔鼠在P14-P60血浆LH浓度下降，雌性仔鼠在P14-P60血浆LH浓度下降，雌性仔鼠在P14-P60血浆LH浓度下降。雌性动物在P14时血浆睾酮/雌二醇浓度升高，雄性动物在P14时血浆雌二醇浓度升高。因此，在产前关键时期通过LPS治疗激活母体免疫系统导致青春期前和青春期后生活中GnRH和LH水平降低，青春期前性类固醇失衡，以及雌性后代性成熟延迟。
Postnatal treatment with bacterial endotoxin lipopolysaccharide (LPS) changes the activity of the hypothalamic-pituitary-gonadal (HPG) axis and the gonadotropin-releasing hormone (GnRH) surge in rats. Exposure to an immune challenge in the critical periods of development has profound and long-lasting effects on the stress response, immune, metabolic, and reproductive functions. Prenatal LPS treatment delays the migration of GnRH neurons associated with increased cytokine release in maternal and fetal compartments. We investigated the effects of a single maternal exposure to LPS (18g/kg, i.p.) on day 12 (embryonic day (E)12) of pregnancy on reproductive parameters in rat offspring. Hypothalamic GnRH content, plasma luteinizing hormone (LH), testosterone, and estradiol concentrations were measured in both male and female offsprings at different stages of postnatal development by RIA and ELISA (n=10 each per group). Body weight and in females day of vaginal opening (VO) were recorded. In offspring exposed to LPS prenatally, compared with controls, body weight was decreased in both sexes at P5 and P30; in females, VO was delayed; hypothalamic GnRH content was decreased at postnatal days 30-60 (P30-P60) in both sexes; plasma LH concentration was decreased at P14-P60 in females; plasma concentrations of testosterone/estradiol were increased at P14 in females, and plasma estradiol was increased at P14 in males. Hence activation of the maternal immune system by LPS treatment at a prenatal critical period leads to decreased GnRH and LH levels in pre- and postpubertal life and sex steroid imbalance in the prepubertal period, and delayed sexual maturation of female offspring.