Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice
Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice
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DOI：
10.1210/me.15.1.172
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发表时间：
2001-01-01
影响因子：
--
通讯作者：
Huhtaniemi, I
中科院分区：
文献类型：
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作者：
Zhang, FP;Poutanen, M;Huhtaniemi, I
为了进一步研究促性腺激素在生殖功能中的作用，我们通过同源重组使LHR基因第11外显子失活，产生了LHR基因敲除小鼠。LuRKO雄性和雌性出生时表型正常，睾丸、卵巢和生殖器结构与它们的野生型(WT)后代难以区分。出生后，LuRKO雄鼠的睾丸生长和下降、外生殖器和附性器官成熟受阻，精子发生受阻于圆形精细胞期。间质细胞的数量和数量均显著减少。LuRKO雌鼠出生后外生殖器和子宫也不发达，阴道开放年龄推迟5-7天。卵巢(-/-)较小，组织学分析显示卵泡发育至有腔早期，但未见排卵前卵泡或黄体。两性性腺激素分泌减少，这也反映在附性器官重量受到抑制和促性腺激素水平升高上。LuRKO配对小鼠睾丸生殖细胞减数分裂的完成与其他低促性腺激素/隐睾鼠模型不同，提示FSH在这一过程中发挥了作用。在女性中，FSH似乎从腔前到腔早期刺激卵泡发育，而促黄体生成素是这一阶段之后的刺激物。因此，在每个性别中，宫内性分化独立于促黄体生成素的作用，但它在出生后对达到性成熟具有至关重要的作用。LuRKO小鼠是最近特征的具有失活LHR突变的人类患者的近表型，尽管LuRKO雄性缺乏假两性，表明该物种的宫内性分化不依赖于促黄体生成素的作用。
To study further the role of gonadotropins in reproductive functions, we generated mice with LH receptor (LHR) knockout (LuRKO) by inactivating, through homologous recombination, exon 11 on the LHR gene. LuRKO males and females were born phenotypically normal with testes, ovaries, and genital structures indistinguishable from their wild-type (WT) littermates. Postnatally, testicular growth and descent, and external genital and accessory sex organ maturation, were blocked in LuRKO males, and their spermatogenesis was arrested at the round spermatid stage. The number and sire of Leydig cells were dramatically reduced. LuRKO females also displayed underdeveloped external genitalia and uteri postnatally, and their age of vaginal opening was delayed by 5-7 days. The (-/-) ovaries were smaller, and histological analysis revealed follicles up to the early antral stage, but no preovulatory follicles or corpora lutea. Reduced gonadal sex hormone production was found in each sex, as was also reflected by the suppressed accessory sex organ weights and elevated gonadotropin levels. Completion of meiosis of testicular germ cells in the LuRKO mates differs from other hypogonadotropic/cryptorchid mouse models, suggesting a role for FSH in this process. In females, FSH appears to stimulate developing follicles from the preantral to early antral stage, and LH is the stimulus beyond this stage. Hence, in each sex, the intrauterine sex differentiation is independent of LH action, but it has a crucial role postnatally for attaining sexual maturity. The LuRKO mouse is a close phenocopy of recently characterized human patients with inactivating LHR mutations, although the lack of pseudohermaphroditism in LuRKO males suggests that the intrauterine sex differentiation in this species is not dependent on LH action.