Age-related uterine and ovarian hypertrophy in FSH receptor knockout and FSHβ subunit knockout mice
Age-related uterine and ovarian hypertrophy in FSH receptor knockout and FSHβ subunit knockout mice
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DOI：
10.1530/reprod/125.2.165
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发表时间：
2003-02-01
期刊：
影响因子：
3.8
通讯作者：
Charlton, HM
中科院分区：
文献类型：
--
作者：
Abel, MH;Huhtaniemi, I;Charlton, HM
编码促卵泡激素FSH受体（FSHR）敲除（KO）或其配体（FSHbetaKO）的基因被破坏的雌性小鼠是不育的。这些小鼠的卵巢显着小于杂合子同窝出生的小鼠，但显着大于相同年龄的性腺功能减退的小鼠。所有三种突变体的子宫质量均< 6 mg，与杂合小鼠相比显着减少。在1岁时，63%的FSHRKO雌性和88%的FSHbetaKO雌性的子宫质量增加到>12 mg。尽管子宫大小增加，但无收缩性证据：子宫松弛，对电刺激或药物刺激无反应。在发生子宫生长的大多数雌性动物中，有证据表明卵巢生长伴间质组织肥大，出现卵巢囊肿以及上皮和管状内含物。在任何年龄的性腺功能减退（hpg）小鼠中或在FSH突变与hpg背景交配的1岁雌性中，均无子宫或卵巢肥大的证据。在1岁的突变型子宫肥大女性中，血浆LH浓度与子宫质量呈负相关。子宫较大的FSHRKO和FSHbetaKO雌性动物的卵巢切除术导致子宫质量降低和LH血浆浓度升高。FSHbetaKO小鼠中卵巢病理学的小鼠数量（令人想起在人类中发现的浆液性卵巢腺癌）显著更多，表明FSHbetaKO雌性动物卵巢细胞上存在完整的FSH受体可能允许卵巢的组成性基础刺激，这在缺乏FSH受体的小鼠中不存在。
Female mice in which the gene encoding the follicle-stimulating hormone FSH receptor (FSHR) knockout (KO) or its ligand (FSHbetaKO) have been disrupted were infertile. Ovaries of these mice were significantly smaller than those of heterozygous littermates but significantly larger than those of hypogonadal mice of the same age. Uterine masses in all three mutants were < 6 mg, significantly reduced compared with heterozygous mice. At 1 year of age uterine mass had increased to >12 mg in 63% of FSHRKO females and 88% of FSHbetaKO females. Despite the increase in uterine size there was no evidence of contractility: uteri were flaccid and unresponsive to electrical or pharmacological stimulation. In most females in which uterine growth had occurred there was evidence of ovarian growth with hypertrophy of the interstitial tissue, occurrence of ovarian cysts and epithelial and tubular inclusions. There was no evidence of uterine or ovarian hypertrophy in hypogonadal (hpg) mice at any age or in 1 year old females in which the FSH mutations were bred onto the hpg background. There was an inverse correlation of plasma LH concentrations and uterine mass in 1 year old mutant females with uterine hypertrophy. Ovariectomy of both FSHRKO and FSHbetaKO females with large uteri resulted in decreased uterine mass and increased plasma concentration of LH. The number of mice with ovarian pathology, reminiscent of the serous ovarian adenocarcinomas found in humans, was significantly greater in the FSHbetaKO mice, indicating that the presence of an intact FSH receptor on ovarian cells of FSHbetaKO females may allow constitutive basal stimulation of the ovary, which is absent in mice lacking FSH receptors.