Kondoh Eiji, Okamoto Takako, Higuchi Toshihiro, Tatsumi Keiji, Baba Tsukasa, Murphy Susan K, Takakura Kenji, Konishi Ikuo, Fujii Shingo
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan.
Hum Reprod. 2009 Apr;24(4):945-53. doi: 10.1093/humrep/den461. Epub 2008 Dec 20.
Although stress is known to disturb natural fertility through the inhibition of the hypothalamic-pituitary-gonadal (HPG) axis, the impact of stress on infertile women who receive exogenous gonadal hormones is not well defined. This is probably due to lack of experimental models for evaluating the impacts of stress through an ovarian-independent pathway. The objective of this study was to investigate the possible impact of stress on uterine receptivity, independent of HPG axis dysfunction, using a mouse implantation model maintained with hormone supplementation.
Blastocysts from donor mice were transferred into the uterine lumen of ovariectomized (OVX) Balb/c female recipient mice following supplementation with estradiol and progesterone. The recipients were divided into two groups: those exposed (stress group) or not exposed (control group) to intermittent sonic exposure prior to embryo transfer (ET). The number of implantation sites (IS) was compared between these groups. Microarray analysis was performed to elucidate stress-induced molecular alterations in uteri during the implantation period. Sequential gene expression of leukemia inhibitory factor (Lif), an estradiol-inducible gene, was also analyzed using real-time PCR.
A non-mating OVX model with satisfactory implantation rates was established. The number of IS in the stress group (n = 20) was significantly less than that in the control group (n = 18) (Mann-Whitney test, P = 0.0375). Implantation-related genes and ovarian-hormone-responsive genes were repressed in the stress group despite ovarian hormone supplementation. The expression of Lif was suppressed in the stress group.
Stress can cause decreased uterine receptivity through an ovarian-independent pathway.
尽管已知压力会通过抑制下丘脑-垂体-性腺（HPG）轴干扰自然生育能力，但压力对接受外源性性腺激素的不孕女性的影响尚不清楚。这可能是由于缺乏通过卵巢非依赖途径评估压力影响的实验模型。本研究的目的是使用补充激素维持的小鼠着床模型，研究压力对子宫容受性的可能影响，而不考虑HPG轴功能障碍。
在补充雌二醇和孕酮后，将供体小鼠的囊胚移植到去卵巢（OVX）的Balb/c雌性受体小鼠的子宫腔内。受体分为两组：在胚胎移植（ET）前接受间歇性声音暴露的（应激组）和未接受暴露的（对照组）。比较两组的着床部位（IS）数量。进行微阵列分析以阐明着床期子宫内压力诱导的分子变化。还使用实时PCR分析了雌二醇诱导基因白血病抑制因子（Lif）的序列基因表达。
建立了具有满意着床率的非交配OVX模型。应激组（n = 20）的IS数量明显少于对照组（n = 18）（Mann-Whitney检验，P = 0.0375）。尽管补充了卵巢激素，但应激组中与着床相关的基因和卵巢激素反应基因受到抑制。应激组中Lif的表达受到抑制。
压力可通过卵巢非依赖途径导致子宫容受性降低。
