Oktay K, Newton H, Mullan J, Gosden R G
Centre for Reproduction, Growth & Development, School of Medicine, University of Leeds, West Yorkshire, UK.
Hum Reprod. 1998 May;13(5):1133-8. doi: 10.1093/humrep/13.5.1133.
In contrast to the many detailed studies of Graafian follicles, the biology of small follicles in the human ovary is poorly understood and the trigger for follicular growth initiation remains unknown. No practical model exists to study preantral follicle growth in the human because of their slow growth rate and lack of an effective culture system. We therefore tested ovarian xenografts as a new strategy to study the early stages of ovarian follicular growth in vivo. Mice homozygous for severe combined immunodeficiency (SCID) and hypogonadism (hpg) received human ovarian xenografts under their kidney capsules. Follicle growth was assessed by morphology and proliferating cell nuclear antigen (PCNA) immunostaining. The grafts were recovered after 11 (short-term) and 17 weeks (long-term), and serially sectioned. During the last 6 weeks of long-term grafting, mice were randomized to receive either placebo or 1 IU of purified follicle stimulating hormone (FSH) s.c. on alternating days. After 11 weeks of grafting, the most advanced follicles had a maximum of two granulosa cell layers. In the absence of FSH administration, follicles did not progress beyond the two-layer stage even after 17 weeks of grafting, and the oestradiol levels remained undetectable. In the FSH-treated long-term grafts, follicles had grown to antral stages and resulted in oestradiol levels as high as 2070 pmol/l. Growth initiation indices did not differ between control and FSH-treated grafts. This study demonstrates that follicles can survive and grow in human ovarian tissue grafted under the renal capsules of immunodeficient mice for at least 17 weeks, and indicate that xenograft models are potentially useful for studying human follicle development. Using this physiological model, we showed that FSH is required for follicle growth beyond the two-layer stage, although growth initiation is independent of gonadotrophin stimulation.
与对格拉夫卵泡的众多详细研究形成对比的是，人类卵巢中小卵泡的生物学特性了解甚少，卵泡生长启动的触发因素仍然未知。由于人类窦前卵泡生长速度缓慢且缺乏有效的培养系统，目前尚无用于研究其生长的实用模型。因此，我们测试了卵巢异种移植作为一种在体内研究卵巢卵泡生长早期阶段的新策略。严重联合免疫缺陷（SCID）和性腺功能减退（hpg）的纯合子小鼠在其肾包膜下接受了人类卵巢异种移植。通过形态学和增殖细胞核抗原（PCNA）免疫染色评估卵泡生长。在11周（短期）和17周（长期）后取出移植物，并进行连续切片。在长期移植的最后6周，将小鼠随机分组，隔天皮下注射安慰剂或1 IU纯化促卵泡激素（FSH）。移植11周后，最先进的卵泡最多有两层颗粒细胞。在未给予FSH的情况下，即使移植17周后，卵泡也未超过两层阶段，雌二醇水平仍无法检测到。在接受FSH治疗的长期移植物中，卵泡已生长至窦状阶段，雌二醇水平高达2070 pmol/l。对照移植物和接受FSH治疗的移植物之间的生长启动指数没有差异。这项研究表明，卵泡可以在免疫缺陷小鼠肾包膜下移植的人类卵巢组织中存活并生长至少17周，这表明异种移植模型可能有助于研究人类卵泡发育。使用这种生理模型，我们表明卵泡生长超过两层阶段需要FSH，尽管生长启动独立于促性腺激素刺激。
