Emergence of uterine pathology during accelerated biological aging in FSH receptor-haploinsufficient mice
Emergence of uterine pathology during accelerated biological aging in FSH receptor-haploinsufficient mice
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DOI：
10.1210/en.2001-211402
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发表时间：
2002-09-01
期刊：
影响因子：
4.8
通讯作者：
Sairam, MR
中科院分区：
文献类型：
--
作者：
Danilovich, N;Roy, I;Sairam, MR
一个功能齐全的FSH受体(FSHR)是卵泡发育和生育所必需的。FSHR缺失的女性由于卵泡成熟、排卵失败和雌激素缺乏而不育。由于FSHR单倍体不足的雌性也开始表现出与年龄相关的生殖缺陷，模拟生物衰老，我们调查了这些小鼠子宫中发生的变化。12个月大的FSHR+/-小鼠的子宫重量增加了2倍，大多数退休饲养者(那些比我们的野生型雌性更早停止繁殖的人)出现了单侧子宫肿块，看起来类似于几种也发生在女性身上的异常，并与不孕不育有关。奇怪的是，大多数异常都发生在右角。高达25%的处女FSHR单倍体缺陷小鼠也出现了病理改变。这些转变在任何年龄的野生型小鼠和雌激素缺乏FSHR缺失的雌性小鼠中都不存在。在单倍体不足的女性中，雌激素和孕酮降低，而睾酮在循环中升高1岁。FSHR单倍体缺陷小鼠在子宫中出现孕激素受体A和B亚型的失衡。这种孕激素受体的改变和子宫中促黄体生成素受体的增加可能是导致子宫病变高发的原因之一。血管生成、血管异常和子宫腺肌病在子宫角出现病理性肿块。FSHR单倍体缺陷小鼠可能有助于理解诱导子宫病理和组织模式的分子基础。
A fully functional FSH receptor (Fshr) is required for ovarian follicular development and fertility. Fshr null females are sterile because of failure of follicular maturation, ovulation, and estrogen deficiency. Because Fshr-haploinsufficient females also begin to show age-dependent reproductive deficits that mimic biological aging, we have investigated the changes that occur in the uterus of these mice. The uterine weight in 12-month-old Fshr +/- mice increased 2-fold, and most retired breeders (those that stopped breeding earlier than our wildtype females) developed unilateral uterine masses that appeared similar to several abnormalities that also occur in women and associated with infertility. Curiously, there was a tendency for most of the abnormality to occur in the right horn. Up to 25% of the virgin Fshr-haploinsufficient mice also developed pathology. These transformations were not present in either wild-type mice or the estrogen-deficient Fshr null females at any age. In haploinsufficient females, estrogen and progesterone were reduced and testosterone was elevated in circulation by 1 yr. Fshr-haploinsufficient mice developed an imbalance of progesterone receptor isoforms A and B in the uterus. This alteration of progesterone receptors along with an increase in LH receptors in the uterus may contribute to the induction of high frequency of uterine pathology. Angiogenesis, vascular abnormality, and adenomyosis appeared to be increased in the uterine horn bearing pathological mass. The Fshr-haploinsufficient mice might help in understanding the molecular basis of induction of uterine pathology and tissue patterning.