Stress affects uterine receptivity through an ovarian-independent pathway.
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.
Kondoh
Eiji
E
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto 606-8507, Japan.
Okamoto
Takako
T
Higuchi
Toshihiro
T
Tatsumi
Keiji
K
Baba
Tsukasa
T
Murphy
Susan K
SK
Takakura
Kenji
K
Konishi
Ikuo
I
Fujii
Shingo
S
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*
D017931:DNA Primers; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D011374:Progesterone; D004958:Estradiol