title: In vivo infusion of interleukin-1beta and chorionic gonadotropin induces endometrial changes that mimic early pregnancy events in the baboon.
abstract: Both human chorionic gonadotropin (hCG) and IL-1beta induce changes in the endometrium that are associated with the establishment of pregnancy. We investigated the synergistic effect of these two embryonic signals on endometrial function using a baboon model of simulated pregnancy. Recombinant hCG (30 IU/d) was infused between d 6 and 10 post ovulation (PO) to mimic blastocyst transit. On the expected day of implantation (d 10 PO), IL-1beta (12 ng/d) or IL-1 receptor antagonist (IL-1Ra; 12 ng/d) was infused for an additional 5 d. Endometria were harvested on d 15 PO. Both hCG and hCG plus IL-1beta induced marked differences in the distribution of alpha-smooth muscle actin, proliferation marker Ki67, decidualization marker IGF-binding protein-1, and cyclooxygenase-1. The most marked effect of IL-1beta was the induction of IGF-binding protein-1 protein in stromal cells close to the apical surface, whereas cyclooxygenase-1 was down-regulated in the glandular epithelium. Protein arrays of uterine flushings showed significant suppression of death receptors, Fas and TNF receptor 1, in the hCG- with or without IL-1beta-treated groups, suggesting an inhibition of apoptosis. Additionally, cytotoxic T lymphocyte antigen-4, matrix metalloproteinase-3, and IL-4 were suppressed in treated animals compared with controls. However, no differences were observed in cytokine profile between hCG-treated and hCG- plus IL-1beta-treated baboons. This study confirms that in preparation for pregnancy, the primate endometrium undergoes both morphological and functional changes, which are modulated by hCG and IL-1beta, that lead to the inhibition of apoptosis and the development of an immunotolerant environment. These changes suggest that infusion of IL-1beta at the time of implantation into the nonpregnant baboon treated with hCG synergizes with hCG and mimics the early endometrial events associated with the presence of an embryo.
authors.affiliation: Department of Obstetrics and Gynecology, University of Illinois, 820 South Wood Street (M/C 808), Chicago, Illinois 60612-7313, USA. zstrakov@uic.edu
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Strakova
authors.forename: Patricia
authors.initials: P
authors.lastname: Mavrogianis
authors.forename: Xuemei
authors.initials: X
authors.lastname: Meng
authors.forename: Julie M
authors.initials: JM
authors.lastname: Hastings
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Jackson
authors.forename: Paula
authors.initials: P
authors.lastname: Cameo
authors.forename: Allison
authors.initials: A
authors.lastname: Brudney
authors.forename: Oluwatoyin
authors.initials: O
authors.lastname: Knight
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D023421:Models, Animal; D010215:Papio; D011388:Prolactin / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011555:Pseudopregnancy / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000199:Actins; D006063:Chorionic Gonadotropin; D016207:Cytokines; D018970:Insulin-Like Growth Factor Binding Protein 1; D007375:Interleukin-1; D019394:Ki-67 Antigen; D011388:Prolactin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases