Sibug R M, Datson N, Tijssen A M I, Morsink M, de Koning J, de Kloet E R, Helmerhorst F M
Division of Medical Pharmacology, Leiden Amsterdam Center for Drug Research/Leiden University Medical Center, The Netherlands.
Hum Reprod. 2007 Jan;22(1):75-82. doi: 10.1093/humrep/del363. Epub 2006 Oct 19.
Controlled ovarian stimulation (COS) with urinary gonadotrophins but not recombinant gonadotrophins, adversely affect the implantation process. In this study, we investigated the effects of urinary and recombinant gonadotrophins on gene expression profiles at implantation sites during the mouse peri-implantation period and the possible molecular mechanisms involved in the detrimental effects of urinary gonadotrophins using microarray technology.
Adult female CD1 mice were treated with (i) urinary human FSH (hFSH) and urinary HCG, (ii) recombinant hFSH and recombinant human LH or (iii) saline. Gene expression profiling with GeneChip mouse genome 430 2.0 arrays, containing 45 101 probe sets, was performed using implantation sites on embryonic day 5. Data were statistically analysed using Significance Analysis of Microarrays. Ten genes from the microarray analysis were selected for validation using quantitative RT-PCR (qRT-PCR). A parallel group of pregnant mice was allowed to give birth to study the effect of gonadotrophins on resorption.
Urinary gonadotrophins differentially up-regulated the expression of 30 genes, increased resorption and reduced litter size, whereas recombinant gonadotrophins did not. Nine of the 10 genes were confirmed by qRT-PCR.
Urinary gonadotrophins, but not recombinant gonadotrophins, exerted differential effects on gene expression during the murine peri-implantation period. These findings might contribute to improve protocols for COS, leading to higher successful pregnancy rates.
使用尿促性腺激素而非重组促性腺激素进行控制性卵巢刺激（COS）会对植入过程产生不利影响。在本研究中，我们利用微阵列技术研究了尿促性腺激素和重组促性腺激素对小鼠植入前期植入部位基因表达谱的影响，以及尿促性腺激素产生有害作用可能涉及的分子机制。
成年雌性CD1小鼠分别接受以下处理：（i）尿源性人促卵泡激素（hFSH）和尿源性人绒毛膜促性腺激素（HCG）；（ii）重组hFSH和重组人促黄体生成素（LH）；或（iii）生理盐水。在胚胎第5天使用植入部位，通过包含45101个探针组的基因芯片小鼠基因组430 2.0阵列进行基因表达谱分析。使用微阵列显著性分析对数据进行统计学分析。从微阵列分析中选择10个基因，使用定量逆转录聚合酶链反应（qRT-PCR）进行验证。另一组怀孕小鼠分娩以研究促性腺激素对吸收的影响。
尿促性腺激素使30个基因的表达差异上调，增加了吸收并减少了窝产仔数，而重组促性腺激素则没有。10个基因中的9个通过qRT-PCR得到证实。
尿促性腺激素而非重组促性腺激素在小鼠植入前期对基因表达产生了不同影响。这些发现可能有助于改进COS方案，从而提高成功妊娠率。
