title: Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice.
abstract: Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear. In this study, we first demonstrated that ovarian stimulation using hCG alone impairs implantation, decidualization and fetal development of mice by generating abnormal ovarian hormone levels. We also showed that ovarian hormone levels were altered because of changes in the levels of the enzymes involved in their synthesis in the follicles and corpora lutea. Furthermore, we determined that anomalous ovarian hormone secretion induced by ovarian stimulation alters the spatiotemporal expression of progesterone receptors and their downstream genes, especially in the uterine epithelium. Epithelial estrogenic signaling and cell proliferation were promoted on the day of implantation in stimulated mice and these changes led to the failure of uterine transition from the prereceptive to the receptive state. Collectively, our findings indicate that ovarian stimulation using hCG induces an imbalance in steroid hormone secretion, which causes a failure of the development of uterine receptivity and subsequent implantation and decidualization by altering the expression of steroid receptors and their downstream signaling associated with embryo implantation.
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ezoe
authors.affiliation: Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors.forename: Takiko
authors.initials: T
authors.lastname: Daikoku
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan k-kato@towako.net a-yabuuchi@towako-kato.com.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yabuuchi
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Murata
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Kawano
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okuno
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Kato Ladies Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan k-kato@towako.net a-yabuuchi@towako-kato.com.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003656:Decidua / Q000187:drug effects*; D010064:Embryo Implantation / Q000187:drug effects*; D004967:Estrogens / Q000097:blood; D005260:Female; D008813:Mice, Inbred ICR; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D010062:Ovulation Induction; D011374:Progesterone / Q000097:blood; D012102:Reproductive Control Agents / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D006063:Chorionic Gonadotropin; D004967:Estrogens; D012102:Reproductive Control Agents; D011374:Progesterone
keywords: decidualization; embryo implantation; hCG; ovarian stimulation; steroid receptor