title: Stress affects uterine receptivity through an ovarian-independent pathway.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Stress can cause decreased uterine receptivity through an ovarian-independent pathway.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kondoh
authors.forename: Takako
authors.initials: T
authors.lastname: Okamoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Keiji
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Kenji
authors.initials: K
authors.lastname: Takakura
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.forename: Shingo
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D010064:Embryo Implantation; D004624:Embryo Transfer; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007246:Infertility / Q000503:physiopathology; D053605:Leukemia Inhibitory Factor / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D023421:Models, Animal; D009622:Noise / Q000009:adverse effects; D020411:Oligonucleotide Array Sequence Analysis; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage; D013312:Stress, Physiological; D014599:Uterus / Q000502:physiology*
chemical_list: D017931:DNA Primers; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D011374:Progesterone; D004958:Estradiol