Andreu C, Parborell F, Vanzulli S, Chemes H, Tesone M
Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
Mol Reprod Dev. 1998 Nov;51(3):287-94. doi: 10.1002/(SICI)1098-2795(199811)51:3<287::AID-MRD8>3.0.CO;2-L.
The purpose of this study was to evaluate the effects of GnRH-analog (Leuprolide acetate, LA) administration on follicular luteinization in equine chorionic gonadotropin plus human chorionic gonadotropin (eCG + hCG)-superovulated prepubertal treated rats. Results indicate that LA treatment decreases circulating levels of progesterone (P) and P accumulation in collagenase-dispersed ovarian cell cultures, though estradiol (E2) production is increased. These data suggest that cells from the LA group may be less luteinized following gonadotropin treatment. Studies performed on histological ovarian sections after different times of eCG administration showed that LA injections produce lower amounts of corpora lutea and antral follicles, and a greater number of atretic and preantral follicles. The basal and LH-stimulated P and progestagen accumulations are decreased in incubations of corpora lutea isolated from the LA group. In addition, the mitochondrial cholesterol side-chain cleavage (P450SCC) levels in corpora lutea from LA-treated rats are reduced, indicating that the decrease in P production observed is due in part to an alteration in the steroidogenic luteal capability. Immunocytochemical localization of nuclei exhibiting DNA fragmentation by the technique of terminal deoxynucleotidyl transferase end-labeling showed that LA treatment causes an increase in the number of apoptotic cells in preantral and antral follicles at all times studied (1, 2, 4, or 7 days of LA administration). A similar effect, though less pronounced, was observed in corpora lutea. It is concluded that LA treatment produces a failure in the steroidogenic luteal capability and an increase of apoptotic mechanisms in the ovary, producing as a consequence an interference in the follicular recruitment, growth, and luteinization induced by gonadotropins.
本研究的目的是评估给予促性腺激素释放激素类似物（醋酸亮丙瑞林，LA）对经马绒毛膜促性腺激素加人绒毛膜促性腺激素（eCG + hCG）超排处理的青春期前大鼠卵泡黄素化的影响。结果表明，LA处理可降低孕酮（P）的循环水平以及胶原酶分散的卵巢细胞培养物中P的积累，不过雌二醇（E2）的产生增加。这些数据表明，LA组的细胞在促性腺激素处理后可能黄素化程度较低。对给予eCG不同时间后的卵巢组织切片进行的研究表明，注射LA可使黄体和窦状卵泡数量减少，闭锁卵泡和窦前卵泡数量增多。从LA组分离的黄体在孵育时，基础及促黄体生成素刺激的P和孕激素积累均减少。此外，LA处理大鼠的黄体中线粒体胆固醇侧链裂解酶（P450SCC）水平降低，表明观察到的P产生减少部分归因于黄体类固醇生成能力的改变。通过末端脱氧核苷酸转移酶介导的缺口末端标记技术对显示DNA片段化的细胞核进行免疫细胞化学定位，结果表明，在研究的所有时间点（LA给药1、2、4或7天），LA处理均导致窦前卵泡和窦状卵泡中凋亡细胞数量增加。在黄体中也观察到类似的效应，不过不太明显。结论是，LA处理导致黄体类固醇生成能力受损，卵巢中凋亡机制增加，从而干扰了促性腺激素诱导的卵泡募集、生长和黄素化。
