In vivo infusion of interleukin-1beta and chorionic gonadotropin induces endometrial changes that mimic early pregnancy events in the baboon.
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.
Strakova
Zuzana
Z
Department of Obstetrics and Gynecology, University of Illinois, 820 South Wood Street (M/C 808), Chicago, Illinois 60612-7313, USA. zstrakov@uic.edu
Mavrogianis
Patricia
P
Meng
Xuemei
X
Hastings
Julie M
JM
Jackson
Kevin S
KS
Cameo
Paula
P
Brudney
Allison
A
Knight
Oluwatoyin
O
Fazleabas
Asgerally T
AT
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*
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