Effect of insulin-like growth factor system on luteinising angiogenesis

by Selleckchem | Jun 21 2023

Preovulatory follicle growth and the luteal transition requires intense angiogenesis. This enables progesterone production to increase sufficiently to support a pregnancy. Inadequate follicular or luteal vascularisation can lead to reduced ovarian function and thus compromise fertility. Insulin-like growth factor 1 (IGF1) and IGF2 regulate multiple ovarian processes and are key links between an animal's reproductive and metabolic status. This study investigated the role that the IGF system plays in regulating luteinising follicular endothelial cell (EC) networks and progesterone production in vitro. Bovine luteinising follicular angiogenesis cultures were treated with 1) LR3-IGF1 (10 or 100ng/ml) under basal and angiogenic-stimulated conditions or 2) IGF1 receptor inhibitor (picropodophyllin (PPP); 1µM) in the presence or absence of LR3-IGF1, IGF2, or combined LR3-IGF1+IGF2 (10ng/ml). EC networks were quantified by von Willebrand factor immunohistochemistry. Progesterone production was analysed by ELISA and cell proliferation was determined by MTT assay. LR3-IGF1 had limited effects on EC growth parameters, whilst PPP (p<0.001) markedly reduced EC growth parameters (by 60-70%). Cell proliferation was slightly increased (by 3-5%) by LR3-IGF1 (p<0.001). LR3-IGF1 had variable effects on progesterone production, whilst PPP reduced progesterone concentration (p<0.001) with or without LR3-IGF1 or IGF2 alone or in combination. IGF1 was detected in cell conditioned media and was increased by LH (50ng/ml) (p<0.001). In conclusion, exogenous IGF1 and IGF2 had minimal effects on luteinising follicular angiogenesis and progesterone production, but the inhibitory effect of the IGFR1 inhibitor (PPP) suggests that IGF1 receptor signalling is critical for the development of EC networks and progesterone production in luteinising follicular cells.

Comments:

The study investigated the role of the insulin-like growth factor (IGF) system in regulating luteinizing follicular endothelial cell (EC) networks and progesterone production in vitro using bovine luteinizing follicular angiogenesis cultures. The researchers aimed to understand the importance of the IGF system in supporting the intense angiogenesis required for preovulatory follicle growth and the luteal transition, which are crucial for adequate progesterone production and fertility.

The researchers treated the angiogenesis cultures with LR3-IGF1 (at concentrations of 10 or 100 ng/ml) under both basal conditions and angiogenic-stimulated conditions. They also used an IGF1 receptor inhibitor called picropodophyllin (PPP) at a concentration of 1 µM, either alone or in combination with LR3-IGF1, IGF2, or combined LR3-IGF1+IGF2 (all at a concentration of 10 ng/ml). They assessed EC network formation using von Willebrand factor immunohistochemistry, measured progesterone production through enzyme-linked immunosorbent assay (ELISA), and evaluated cell proliferation using the MTT assay.

The study findings revealed that LR3-IGF1 had limited effects on EC growth parameters. However, the IGF1 receptor inhibitor (PPP) significantly reduced EC growth parameters by 60-70%. LR3-IGF1 slightly increased cell proliferation by 3-5%. LR3-IGF1 showed variable effects on progesterone production, while PPP reduced progesterone concentration with or without LR3-IGF1 or IGF2 alone or in combination.

The researchers also detected the presence of IGF1 in the conditioned media of the cells, and its levels were increased by luteinizing hormone (LH) at a concentration of 50 ng/ml.

In conclusion, the study suggests that exogenous IGF1 and IGF2 have minimal effects on luteinizing follicular angiogenesis and progesterone production. However, the inhibitory effect of the IGF1 receptor inhibitor (PPP) indicates that IGF1 receptor signaling plays a critical role in the development of EC networks and progesterone production in luteinizing follicular cells.