生命早期的免疫应激对雌鼠青春期生殖功能的影响  

Influence on pubertal reproductive function in female rats by immune challenge in early life

作　　者：吴雪清[1] 李晓峰[1] 叶碧绿[1] 

机构地区：[1]温州医学院附属第一医院妇产科,325000

出　　处：《中华妇产科杂志》2011年第6期441-445,共5页Chinese Journal of Obstetrics and Gynecology

基　　金：温州市科技计划（H20100071）

摘　　要：目的研究生命早期的免疫应激对雌鼠青春期生殖功能的影响。方法雌性Sprague—Dawley大鼠在出生后第3、5天行腹腔注射脂多糖（50μg/kg）和生理盐水作为实验组和对照组。每周测体质量，生后30d开始监测青春期启动（即阴道口初开放）时间和卵巢周期的变化。生后6周行卵巢切除术，观察卵巢组织形态学的变化（卵泡内膜厚度和各种类型卵泡的数目）；用免疫组化方法测定卵巢交感神经兴奋性的改变[以低亲和力的神经生长因子受体（p75NGFR）的免疫染色强度表示]。结果生命早期的免疫应激（暴露于脂多糖），能延迟阴道口初开放的时间，实验组大鼠为生后（40．6±0．7）d，对照组为生后（38．6±0．6）d，两组比较，差异有统计学意义（P〈0．05）；降低卵巢正常周期的比例，实验组为26．1％，对照组为66．8％，两组比较，差异有统计学意义（P〈0．05）；减少各种类型卯泡的数目，实验组大鼠原始卵泡（610±47）个、初级卵泡（624±41）个、窦前卵泡（183±16）个、窦卯泡（32±4）个，对照组分别为（1181±57）、（960±30）、（260±14）、（79±7）个，分别比较，差异均有统计学意义（P〈0．05）；增加卵泡内膜厚度，实验组及对照组分别为（15．8±0．4）、（11．4±0．3）μm，两组比较，差异有统计学意义（P〈0．05）。实验组大鼠的卵巢p75NGFR免疫染色强度较对照组明显增高（P〈0．05）。结论雌鼠生命早期的免疫应激对其青春期的生殖功能有明显的影响。生命早期的免疫应激可能通过上调卵巢交感神经兴奋性而推迟青春期发育，并减少卵巢正常周期的比例和卯泡储备，使卯泡内膜增厚。Objective To investigate the long-term programming effects on pubertal reproductive function by immunological challenge in early life. Methods Female Sprague-Dawley rats were administered by endotoxin （lipopolysaccharide, LPS） at a dosage of 50 μg/kg and saline intraperitoneally on postnatal day 3 and 5. Body weight was measured weekly. Puberty onset （vaginal opening） and oestrous cyelicity were monitored from postnatal day 30. At the age of 6 weeks, bilateral ovariectomy was performed. The histological and morphological change of the ovaries （ the thickness of the theca interna and the number of different kinds of follicles） were observed and the immunoreactivity of the ovarian sympathetic nerve markers （ low affinity receptor of nerve growth factor, p75NGFR） was evaluated by immune staining. Results Immunological challenge （exposed to LPS） in early life delayed vaginal opening significantly [ LPS-treated （40. 6 ±0. 7 ） days versus controls （38.6±0. 5） days, P 〈 0. 05 ] , decreased the percentage of normal oestrous cyclicity （LPS-treated 26. 1% versus controls 66. 8% , P 〈 0.05 ） , decreased the total number of different types of follicles （ primordial follicles ： LPS-treated 610 ±47 versus controls 1181 ±57, P 〈 0. 05 ; primary follicles ： LPS-treated 624 ±41 versus controls 960 ±30, P 〈0.05; preantral follicles：LPS-treated 183 ±16 versus controls 260 ±14, P 〈 0. 05 ; antra/ follicles ： LPS-treated 32 ±4 versus controls 79 ±7, P 〈 0.05 ） and increased the thickness of the theca interna [ LPS-treated （ 15. 8 ±0. 4） gm versus controls （ 11.4 ±0. 3 ） μm, P 〈 0. 05 ]. The immunostaining of p75NGFR was obviously enhanced in the LPS-treated ovaries when compared with that of controls （ P 〈 0. 05 ） . Conclusions Immunological stress during early critical developmental windows could have long dysfunctional effects on the pubertal reproductive function. It delayed puberty onset, reduced the percentage of the normal oestrous cycles, dec

关 键 词：内毒素类 青春期 生殖 月经周期 卵巢 交感神经系统 大鼠 

分 类 号：R392.1[医药卫生—免疫学]