Lack of accelerated ovarian aging in a follicle-stimulating hormone receptor haploinsufficiency model.
Lack of accelerated ovarian aging in a follicle-stimulating hormone receptor haploinsufficiency model.
复制标题
促卵泡激素受体单倍体不足模型中缺乏加速卵巢老化。
DOI：
10.1016/j.tma.2023.01.001
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发表时间：
2023
影响因子：
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通讯作者：
Benayoun,BéréniceA
中科院分区：
文献类型：
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作者：
Mehalko,Kristen;Kim,Minhoo;Paye,Sanjana;Koh,Kelly;Lu,RyanJ;Benayoun,BéréniceA
卵泡刺激素 (FSH) 和 FSH 受体 (FSHR) 信号传导对于女性终生卵巢和内分泌功能至关重要。此前的研究报道称，雌性小鼠的Fshrhaplo不足导致卵巢加速衰老，包括预期的生育力进行性下降、发情周期不规律、卵泡闭锁增加以及7-9月龄时卵巢早衰。有趣的是，这些表型类似于人类更年期的关键特征，因此 Fshrhaploinsufficiency 被提议作为一种有前途的更年期研究小鼠模型。然而，Fshrhaploinsufficiency 模型尚未得到充分探索，特别是在分子水平上。在这项研究中，我们表征了 aFshr 杂合性敲除等位基因的卵巢和内分泌功能，该等位基因是在 C57BL/6 遗传背景上生成的，作为敲除小鼠计划 (KOMP) 的一部分。根据我们使用繁殖测定、卵巢组织组织学和血清激素定量（即 FSH、AMH、INHA）分析对这些小鼠的分析，KOMPFshr 杂合基因敲除雌性小鼠在生育力和内分泌功能方面并未显示出预期的卵巢衰老表型。我们进一步证实，与野生型相比，KOMPFshr杂合敲除动物的卵巢中Fshris的表达没有改变。总之，我们的数据表明，KOMPFshr 杂合性敲除菌株并不能重现先前报道的与另一种 Fshr 单倍体不足模型相关的卵巢衰老表型。
Follicle-stimulation hormone (FSH) and FSH receptor (FSHR) signaling is essential for lifelong ovarian and endocrine functions in females. Previous studies have reported thatFshrhaploinsufficiency in female mice led to accelerated ovarian aging, including anticipated progressive fertility decline, irregular estrus cycles, increased follicular atresia and premature ovarian failure at 7–9 months of age. Interestingly, these phenotypes resemble key characteristics of human menopause and thusFshrhaploinsufficiency was proposed as a promising research mouse model of menopause. However, theFshrhaploinsufficiency model had not been fully explored, especially at the molecular level. In this study, we characterized the ovarian and endocrine functions of aFshrheterozygous knockout allele that was generated on the C57BL/6 genetic background as part of the Knockout Mouse Project (KOMP). Based on our analyses of these mice using a breeding assay, ovarian tissue histology and serum hormone quantifications (i.e.FSH, AMH, INHA) analyses, the KOMPFshrheterozygous knockout female mice do not show the anticipated phenotypes of ovarian aging in terms of fertility and endocrine function. We further confirmed that the expression ofFshris unaltered in the ovaries of the KOMPFshrheterozygous knockout animals compared to wild-type. Together, our data suggests that the KOMPFshrheterozygous knockout strain does not recapitulate the previously reported ovarian aging phenotypes associated to another model ofFshrhaploinsufficiency.