Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice
Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice
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DOI：
10.1530/rep-11-0336
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发表时间：
2012-02-01
期刊：
影响因子：
3.8
通讯作者：
McNatty, Kenneth P.
中科院分区：
文献类型：
--
作者：
McIntosh, C. Joy;Lawrence, Steve;McNatty, Kenneth P.
转化生长因子β（TGFB）超家族蛋白质骨形态发生蛋白15（BMP 15）和生长分化因子9（GDF 9）对于哺乳动物生育力是必需的。最近的体外证据表明，小鼠BMP 15和GDF 9的前区在分泌后与它们的成熟蛋白相互作用。在这项研究中，我们积极免疫小鼠对这些proregions测试在生育力的潜在体内作用。用BMP 15或GDF 9的N-或C-末端前区肽或全长GDF 9前区蛋白免疫小鼠，每种前区肽均与钥孔血蓝蛋白（KLH）缀合。对于每个免疫组，在免疫后从10只小鼠收集卵巢用于组织学，同时允许另外20只小鼠繁殖并计数窝仔数。为了将这两个实验终点的排卵和生育力数据联系起来，在通过组织学鉴定为排卵期的时间段内将小鼠加入，从而对黄体（CL）进行计数。在整个研究期间，血清中的抗体滴度增加，在BMP 15和GDF 9血清和抗原之间没有观察到交叉反应性。与KLH对照组相比，用N-末端BMP 15前区肽免疫的小鼠具有更少的卵巢CL（P< 0.05），并且产生更小的窝数（P< 0.05）。相反，用全长GDF 9前区免疫的小鼠不仅具有更多的CL（P
The transforming growth factor beta (TGFB) superfamily proteins bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), are essential for mammalian fertility. Recent in vitro evidence suggests that the proregions of mouse BMP15 and GDF9 interact with their mature proteins after secretion. In this study, we have actively immunized mice against these proregions to test the potential in vivo roles on fertility. Mice were immunized with either N- or C-terminus proregion peptides of BMP15 or GDF9, or a full-length GDF9 proregion protein, each conjugated to keyhole limpet hemocyanin (KLH). For each immunization group, ovaries were collected from ten mice for histology after immunization, while a further 20 mice were allowed to breed and litter sizes were counted. To link the ovulation and fertility data of these two experimental end points, mice were joined during the time period identified by histology as being the ovulatory period resulting in to the corpora lutea (CL) counted. Antibody titers in sera increased throughout the study period, with no cross-reactivity observed between BMP15 and GDF9 sera and antigens. Compared with KLH controls, mice immunized with the N-terminus BMP15 proregion peptide had ovaries with fewer CL (P< 0.05) and produced smaller litters (P< 0.05). In contrast, mice immunized with the full-length GDF9 proregion not only had more CL (P