FUNCTIONAL RECOVERY OF THE DEVELOPING RAT OVARY AFTER TRANSPLANTATION - CONTRIBUTION OF THE EXTRINSIC INNERVATION
FUNCTIONAL RECOVERY OF THE DEVELOPING RAT OVARY AFTER TRANSPLANTATION - CONTRIBUTION OF THE EXTRINSIC INNERVATION
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DOI：
10.1210/endo-129-4-1849
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发表时间：
1991-10-01
期刊：
影响因子：
4.8
通讯作者：
OJEDA, SR
中科院分区：
文献类型：
--
作者：
LARA, HE;DEES, WL;OJEDA, SR
这些实验是为了确定移植到异位部位后卵巢功能恢复的神经内分泌机制。将23日龄大鼠的双侧卵巢移植到颈静脉旁的颈部区域。此后每隔一段时间测定血清促性腺激素和血浆免疫反应性抑制素-α水平。于移植后第1周测定血清雌二醇(E_2)。用免疫组织化学方法观察交感神经和感觉神经对卵巢的再支配。根据儿茶酚胺生物合成的限速酶酪氨酸羟化酶(TH)的存在，交感神经被认为是肾上腺素能的，而通过神经肽Y(NPY)或血管活性肠肽(VIP)的免疫反应，交感神经被认为是肽能的。通过P物质(SP)和降钙素基因相关肽(CGRP)免疫反应鉴定感觉神经。移植后48h内，血清黄体生成素和卵泡刺激素水平升高，血浆抑制素水平下降。这些变化与移植后血清E2水平的波动有关，移植后48h下降，第4天回升，第7天恢复到基础水平。摘除移植卵巢后第4天血清E2水平消失，从而证实卵巢移植物是E2的来源。与促黄体生成素相反，移植后至少3周，血清FSH显著升高，21天后下降至基础水平，与抑制素分泌增加相一致。虽然移植后48h发现大量卵泡丢失，但第4天的定量检查显示，大约40%的有腔卵泡没有坏死。移植后21d观察排卵和黄体形成情况。移植后7天，TH、VIP、NPY、SP和CGRP纤维首次检测到移植卵巢的再神经支配。虽然VIP的再支配很稀少，而且只有短暂的分布(7-21天)，但交感(TH，NPY)和感觉(SP，CGRP)纤维的密度在7-28天间增加了2-3倍，此后保持不变。由于这种神经再支配的明显完成恰逢黄体生成素和卵泡刺激素恢复正常水平，因此进行了另一项实验，以确定这两个事件是否存在因果关系。在新生儿期应用神经生长因子抗体阻止卵巢交感神经支配的发育，并照旧进行卵巢自体移植。移植后35天的卵巢检查显示交感神经再支配失败，感觉神经再支配减少。根据黄体的存在判断，虽然排卵能力保持不变，但基础血清中的黄体生成素和卵泡刺激素水平并没有恢复到移植前的水平，这表明卵巢未能完全重建对促性腺激素分泌的负反馈控制。
These experiments were undertaken to define the neuroendocrine mechanisms underlying the recovery of ovarian function after transplantation to an ectopic site. Both ovaries from 23-day-old rats were transplanted to the region of the neck, next to the jugular vein. Serum gonadotropin and plasma immunoreactive inhibin-alpha levels were determined at several intervals thereafter. Serum estradiol (E2) was measured during the first week posttransplantation. Reinnervation of the ovary by sympathetic and sensory nerves was monitored by immunohistochemistry. Sympathetic nerves were identified as adrenergic by the presence of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, and as peptidergic, by their neuropeptide-Y (NPY) or vasoactive intestinal peptide (VIP) immunoreactivity. Sensory nerves were identified by the presence of substance P (SP) and calcitonin-gene related peptide (CGRP) immunoreactivity. Serum LH and FSH increased, and plasma inhibin levels decreased, within 48 h after transplantation. Serum LH reached maximum levels on day 4, decreasing rapidly thereafter to basal values by day 6. These changes were functionally correlated with the posttransplantation fluctuations in serum E2, which decreased at 48 h, rebounded by day 4, and returned to basal values on day 7. Removal of the transplanted ovaries on day 3 resulted in the disappearance of serum E2 levels on day 4, thus confirming the ovarian graft as the source of E2. In contrast to LH, serum FSH remained significantly elevated for at least 3 weeks after transplantation, then decreased to basal levels after day 21, coinciding with the rise in inhibin secretion. Although a substantial loss of follicles was noted 48 h after transplantation, quantitative examination of the changes on day 4 revealed that approximately 40% of antral follicles were not necrotic. Ovulation and formation of corpora lutea were noted 21 days after transplantation. Reinnervation of the transplanted ovary by TH-, VIP-, NPY-, SP-, and CGRP-containing fibers was first detected 7 days after transplantation. Although VIP reinnervation was sparse and only transiently detected (days 7-21), the density of sympathetic (TH, NPY) and sensory (SP, CGRP) fibers increased 2- to 3-fold between days 7-28, remaining unchanged thereafter. Since apparent completion of this reinnervation coincided with reestablishment of normal levels of both LH and FSH, an additional experiment was performed to determine if the two events were causally related. Development of the sympathetic innervation of the ovary was prevented by administration of antibodies to nerve growth factor during neonatal life, and the ovaries were autotransplanted as before. Examination of the ovaries 35 days after transplantation revealed that sympathetic reinnervation had failed to occur and that sensory reinnervation was reduced. Although the capacity to ovulate was maintained, as judged by the presence of corpora lutea, basal serum LH and FSH levels did not return to pretransplantation levels, indicating failure of the ovary to fully reestablish negative feedback control on gonadotropin secretion.The results suggest that reinnervation contributes to the process by which the ovary recovers its functional competence after transplantation to an ectopic site.