Telleria C M, Mezzadri M R, Deis R P
Laboratorio de Reproducción y Lactancia, Consejo Nacional de Investigaciones Científicas (LARLAC-CONICET), Mendoza, Argentina.
Contraception. 1997 Oct;56(4):267-74. doi: 10.1016/s0010-7824(97)00137-6.
Accumulated evidence indicates that the antigestagen mifepristone affects the reproductive axis acting on hypothalamic, pituitary, ovarian, and uterine tissues. The purpose of this study was to further investigate which reproductive functions are impaired by the antagonist, critically compromising the reproductive process, leading to unsuccessful pregnancy. Circulating pituitary and ovarian hormones, sexual receptivity, ovulation, and implantation rates were studied in cycling rats receiving a single dose of mifepristone (1 or 10 mg/kg subcutaneously) at 12:00 proestrus, before luteinizing hormone (LH) stimulation of the ovulatory process. Mifepristone-treated rats had decreased preovulatory surges of LH and prolactin (PRL), and hypersecretion of LH, PRL, and progesterone at estrus. The sexual receptivity was dramatically affected by the antagonist as indicated by the profound decrease in the lordosis response evaluated on the night of proestrus. The number of ovulating animals and the number of oocytes recovered from the oviduct on the morning of estrus were not affected by mifepristone. The low number of rats that succeeded in mating with potent males became pregnant. However, they delivered an average of only two pups at parturition, indicating a failure in the implantation of the fertilized ova, as ovulation was not affected by the antagonist at the dose used. We conclude that a dramatic inhibition of the sexual receptivity and unsuccessful implantation, preceded by a reduction on LH and PRL secretion, are the major components leading to fertility impairment after a single dose of mifepristone administered before the preovulatory surge of LH.
越来越多的证据表明，抗孕激素米非司酮通过作用于下丘脑、垂体、卵巢和子宫组织来影响生殖轴。本研究的目的是进一步探究该拮抗剂会损害哪些生殖功能，严重影响生殖过程，导致妊娠失败。在排卵前促黄体生成素（LH）刺激排卵过程之前，于动情前期12:00给处于发情周期的大鼠皮下注射单剂量米非司酮（1或10 mg/kg），然后研究循环中的垂体和卵巢激素、性接受能力、排卵及着床率。经米非司酮处理的大鼠，LH和催乳素（PRL）的排卵前峰值降低，发情期LH、PRL和孕酮分泌过多。如在动情前期夜间评估的脊柱前凸反应显著降低所示，性接受能力受到该拮抗剂的显著影响。排卵动物的数量以及在发情期早晨从输卵管回收的卵母细胞数量不受米非司酮影响。与强壮雄性成功交配的大鼠数量较少，且成功怀孕。然而，它们在分娩时平均仅产下两只幼崽，表明受精卵着床失败，因为在所使用的剂量下，排卵不受该拮抗剂影响。我们得出结论，在LH排卵前峰值之前单次给予米非司酮后，导致生育能力受损的主要因素是性接受能力受到显著抑制和着床失败，在此之前LH和PRL分泌减少。
