Expression of insulin-like growth factor binding protein-1 (IGFBP-1) mRNA in the ovine uterus throughout the oestrous cycle and early pregnancy

Abstract

Insulin-like growth factors (IGFs) are thought to be important regulators of embryonic and fetal development. The half life, distribution and action of IGFs are modulated by a family of IGF-binding proteins (IGFBP). This study investigated the pattern of IGFBP-1 expression in the ovine uterus during the oestrous cycle and early pregnancy by in situ hybridisation. Uteri were collected from 46 non-pregnant ewes throughout the oestrous cycle and from 12 pregnant ewes between days (D)13 and 22 of gestation. Samples were also obtained on D16-17 from both horns of 5 ewes with unilateral pregnancies following uterine transection. IGFBP-1 expression was quantified as optical density (OD) units from autoradiographs using a Seescan image analysis system. IGFBP-1 mRNA was confined to the luminal epithelium, with a highly significant variation in concentration according to the stage of the cycle. In non-pregnant uteri, IGFBP-1 concentrations were high throughout the late luteal phase and oestrous period, peaking at an OD of 0.76 ± 0.119, but concentrations fell below the detection limit (OD<0.01) by D5 before starting to increase again between D7 and 9. During early pregnancy there was no difference in expression between non-pregnant and pregnant ewes on D13 (OD 0.76 ± 0.065, n=6 vs 0.71 ± 0.070, n=3). As pregnancy progressed there was a significant steady decline in IGFBP-1 expression to 0.04 ± 0.02 on D22. In the transected uteri on D16-17, IGFBP-1 mRNA expression was significantly higher in the pregnant than in the non-pregnant horn (0.44 ± 0.04 vs 0.10 ± 0.02, n=5, P<0.01). In conclusion, the location of the IGFBP-1 suggests that it may play a role in regulating the transfer of IGFs between the endometrium and the uterine lumen. The conceptus may enhance IGFBP-1 expression during early pregnancy. Oestrogen and progesterone may regulate IGFBP-1 expression during the cycle but this requires further investigation.