How does daily treatment with human chorionic gonadotropin induce superovulation in the cyclic hamster?
How does daily treatment with human chorionic gonadotropin induce superovulation in the cyclic hamster?
复制标题
人绒毛膜促性腺激素的日常治疗如何诱导周期性仓鼠超数排卵？
DOI：
10.1095/biolreprod48.1.133
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发表时间：
1993
影响因子：
3.6
通讯作者：
Greenwald,GS
中科院分区：
文献类型：
--
作者：
Greenwald,GS
每日皮下注射从周期第1天（发情期）开始，每天注射2.0 IU hCG，导致仓鼠排卵20.7 ± 0.7个卵，而不是正常的13.3 ± 0.5个卵（SEM）。这与卵泡闭锁率降低有关，因此通常在周期第1天招募的每个卵巢（大腔前阶段）的10个发育卵泡中有更多成熟并继续排卵。hCG处理的卵泡比对照卵泡大，但含有类似数量的DNA/卵泡;窦腔的大小增加占其更大的尺寸。此外，在第2天和第4天，hCG卵泡中的DNA合成显著减少。通过卵泡膜中保留的红细胞数量或卵泡微球摄取判断的卵泡膜血管分布表明，在第2天，hCG治疗动物的卵泡膜血流量显著低于对照组。另一方面，在第1天开始hCG治疗后，血清水平和单个卵泡的体外孵育显示，在第2天及以后，雄烯二酮（A）和雌二醇（E2）水平升高。hCG治疗后，血清E2升高与第3天和第4天血清LH降低相关，而FSH不受影响。为了研究体外类固醇蓄积，从对照组和hCG处理组动物的交替左右卵巢中解剖10个最大的卵泡（发育中的卵泡），并单独孵育，然后将其组织学与类固醇特征进行比较。在基础孵育1小时和添加50 ng LH后，hCG处理的卵泡中A和E2的积累显著高于对照组。孕酮的积累通常没有不同的控制和hCG治疗的卵泡。早期阶段1闭锁卵泡（由组织学判断）仍然能够产生A和E2在体外，与对照卵泡，但是，随着闭锁的进展，卵泡只合成孕酮。这与先前在仓鼠诱导卵泡闭锁模型中观察到的时间模式一致[Greenwald，Biol Reprod 1989; 40：175-181]。由此得出结论，hCG注射导致的超数排卵是由于卵泡膜产生的雄激素通常注定闭锁。对于未处理的周期性仓鼠，卵泡膜雄激素产生的关键时间是周期的前2天。芳香化雄激素然后转化为雌激素，雌激素反过来可以维持窦腔的微环境，这对颗粒细胞的活力至关重要。据推测，在啮齿类动物中，未分化卵泡膜产生的雄激素比正常卵泡膜少，是诱发有腔卵泡闭锁的促发因素，尽管不能排除其他可能性。
Daily s.c. injection of 2.0 IU hCG per day, begun on Day 1 of the cycle (estrus), results in hamsters ovulating 20.7 ± 0.7 eggs instead of the normal number of 13.3 ± 0.5 (SEM). This is associated with a reduced rate of follicular atresia so that more of the 10 developing follicles per ovary (large preantral stages) normally recruited on Day 1 of the cycle mature and go on to ovulate. The hCG-treated follicles were larger than control follicles, but contained similar amounts of DNA/follicle; increased size of the antral cavity accounted for their greater size. Moreover, DNA synthesis was significantly reduced in the hCG follicles on Days 2 and 4. Thecal vascularity as judged by the number of red blood cells retained in the theca or microsphere uptake by follicles indicates that on Day 2, thecal blood flow was significantly lower in the hCG-treated animals than in controls. On the other hand, after hCG treatment begun on Day 1, serum levels and in vitro incubation of individual follicles revealed that on Day 2 and beyond, androstenedione (A) and estradiol (E2) levels were elevated. After hCG treatment, the elevated serum E2correlated with reduced serum LH on Days 3 and 4 whereas FSH was unaffected. To study in vitro steroid accumulation, the 10 largest follicles (the developing follicles) were dissected from alternate left and right ovaries from control and hCG-treated animals and incubated individually, and their histology was then compared with the steroid profiles. Accumulation of A and E2was significantly greater in the hCG-treated follicles than in controls in a 1-h basal incubation and after the addition of 50 ng LH. Progesterone accumulation usually did not differ between the control and hCG-treated follicles. Early stage 1 atretic follicles (judged by histology) were still capable of producing A and E2in vitro, comparable to control follicles; but, as atresia progressed, the follicles synthesized only progesterone. This is consistent with the temporal pattern previously observed in a model of induced follicular atresia in the hamster [Greenwald, Biol Reprod 1989; 40:175–181]. It is concluded that superovulation resulting from hCG injections is due to thecal production of androgens from follicles normally destined for atresia. For the untreated cyclic hamster, the critical time for thecal androgen production is the first 2 days of the cycle. The aromatizable androgens are then converted into estrogens, which in turn may maintain the microenvironment of the antral cavity, which is essential for viability of the granulosa cells. It is postulated that in rodents the undifferentiated theca producing less androgen than normal is the precipitating factor in inducing atresia of antral follicles, although other possibilities cannot be discounted.