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氟维司群消除产前脂多糖诱导的雄性大鼠后代生殖障碍

Abolition of prenatal lipopolysaccharide-induced reproductive disorders in rat male offspring by fulvestrant.

作者信息

Izvolskaia Marina S, Sharova Victoria S, Ignatiuk Vasilina M, Voronova Svetlana N, Zakharova Liudmila A

机构信息

Koltsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.

Moscow State University, Moscow, Russia.

出版信息

Andrologia. 2019 Apr;51(3):e13204. doi: 10.1111/and.13204. Epub 2018 Nov 26.

DOI:10.1111/and.13204
PMID:30474158
Abstract

During prenatal and early postnatal periods of development, multiple environmental factors have profound and long-lasting effects on the immune and reproductive functions. The aim of this study was to investigate the effects of maternal lipopolysaccharide (LPS) exposure (50 mg/kg, i.p.) at day 12 of pregnancy and estradiol antagonist treatment (fulvestrant, 1.5 mg/kg, s.c. in neck) at postnatal days 5-14 (PND5-14) with high estradiol levels on reproductive parameters in adult rat males. Serum steroid concentrations were measured in male offspring at PND80 by ELISA. Body, testis weights and ano-genital distance (AGD) were recorded at different stages of postnatal development. Testis was also processed to cytohistological studies at PND80. Our results demonstrate that body weight was decreased from PND14 to 30 after prenatal LPS treatment and was increased after fulvestrant treatment. AGD was decreased after prenatal LPS treatment and was increased after fulvestrant injections. Testis weight, testosterone level, seminiferous tubule diameter, and number of Sertoli and spermatid cells were also decreased in rats exposed prenatally to LPS and were restored to the normal control level after fulvestrant treatment. According to results, we can conclude that the development of sexual disorders in males after prenatal immune stress is potentiated by estradiol during the pre-pubertal period.

摘要

在产前和产后早期发育阶段,多种环境因素对免疫和生殖功能具有深远且持久的影响。本研究的目的是调查孕期第12天母体暴露于脂多糖(LPS,50毫克/千克,腹腔注射)以及产后第5 - 14天(PND5 - 14)在雌二醇水平较高时给予雌二醇拮抗剂治疗(氟维司群,1.5毫克/千克,颈部皮下注射)对成年雄性大鼠生殖参数的影响。在PND80时通过酶联免疫吸附测定法(ELISA)测量雄性后代的血清类固醇浓度。在产后发育的不同阶段记录体重、睾丸重量和肛门生殖器距离(AGD)。在PND80时还对睾丸进行细胞组织学研究。我们的结果表明,产前LPS处理后,从PND14到30体重下降,而氟维司群处理后体重增加。产前LPS处理后AGD减小,氟维司群注射后AGD增加。产前暴露于LPS的大鼠的睾丸重量、睾酮水平、曲细精管直径以及支持细胞和精子细胞数量也减少,氟维司群处理后恢复到正常对照水平。根据结果,我们可以得出结论,产前免疫应激后雄性性功能障碍的发展在青春期前受到雌二醇的增强作用。

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