Danforth Douglas R, Arbogast Laura K, Friedman Chad I
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio 43210, USA.
Fertil Steril. 2005 May;83(5):1333-8. doi: 10.1016/j.fertnstert.2004.12.030.
To examine the effects of GnRH antagonists on preantral follicle survival in vivo and to investigate whether GnRH antagonist use during cyclophosphamide treatment would protect the ovary and preserve primordial follicle survival in a murine model.
Prospective basic research study.
Research laboratory in an academic medical center.
ANIMAL(S): Adult C57Bl/6 mice (5 to 6 weeks old).
INTERVENTION(S): Mice received either a single injection of GnRH agonist (leuprolide acetate) on study day -10 or injections of the GnRH antagonist (antide or cetrorelix) on study days -3 and 0. Some animals also received the chemotherapeutic agent cyclophosphamide on day 0. All animals were killed by CO2 asphyxiation on day 7. To examine direct vs. indirect effects, some mice received GnRH antagonist under the bursa of one ovary, with the contralateral ovary receiving vehicle. Ovaries were fixed in Kahle's solution; 7-mum tissue sections were stained with Lillie's allochrome, and preantral follicles were counted on every fifth section.
MAIN OUTCOME MEASURE(S): Numbers of primordial, primary, and secondary follicles.
RESULT(S): Systemic administration of both GnRH antagonists caused a significant destruction of primordial follicles compared with control mice. Similar results were obtained whether the antagonists were administered systemically or directly to the ovary. Gonadotropin-releasing hormone agonist had no effect on primordial follicle numbers by itself but reduced the follicular depletion caused by cyclophosphamide.
CONCLUSION(S): In contrast to the effects of GnRH agonists to reduce chemotherapeutic destruction of primordial follicles, GnRH antagonists do not protect the ovary from the damaging effects of cyclophosphamide. More importantly, GnRH antagonists alone deplete primordial follicles in this murine model, likely through a direct effect on the ovary. Whether these observations apply to other species requires further study.
研究促性腺激素释放激素（GnRH）拮抗剂对体内窦前卵泡存活的影响，并探讨在环磷酰胺治疗期间使用GnRH拮抗剂是否能在小鼠模型中保护卵巢并维持原始卵泡的存活。
前瞻性基础研究。
学术医学中心的研究实验室。
成年C57Bl/6小鼠（5至6周龄）。
小鼠在研究第-10天接受单次促性腺激素释放激素激动剂（醋酸亮丙瑞林）注射，或在研究第-3天和第0天接受促性腺激素释放激素拮抗剂（安体舒通或西曲瑞克）注射。一些动物在第0天还接受了化疗药物环磷酰胺。所有动物于第7天通过二氧化碳窒息处死。为了研究直接与间接作用，一些小鼠在一侧卵巢的囊下接受促性腺激素释放激素拮抗剂，对侧卵巢接受赋形剂。卵巢用卡勒氏溶液固定；7微米厚的组织切片用利利氏异染剂染色，每第五张切片计数窦前卵泡。
原始卵泡、初级卵泡和次级卵泡的数量。
与对照小鼠相比，两种促性腺激素释放激素拮抗剂的全身给药均导致原始卵泡的显著破坏。无论拮抗剂是全身给药还是直接注射到卵巢，都得到了类似的结果。促性腺激素释放激素激动剂本身对原始卵泡数量没有影响，但减少了环磷酰胺引起的卵泡耗竭。
与促性腺激素释放激素激动剂减少化疗对原始卵泡破坏的作用相反，促性腺激素释放激素拮抗剂不能保护卵巢免受环磷酰胺的损害作用。更重要的是，在该小鼠模型中，促性腺激素释放激素拮抗剂单独使用会耗尽原始卵泡，可能是通过对卵巢的直接作用。这些观察结果是否适用于其他物种需要进一步研究。
