Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway

Table 1 Changes in gene expression in the OSE induced by 5 μg/ml insulin or 5 μg/ml IGF-I

Gene symbol	Insulin	IGF	Gene symbol	Insulin	IGF
Insulin-Receptor associated proteins			MAPK Pathway
Dok1	−1.24	−4.22	Braf	−1.24	−3.76
Dok2	−2.17	−1.13	Fos	−1.22	2.36
Dok3	−1.79	−14.41	Hras1	−1.04	−2.26
Eif4ebp1	1.63	2.21	Kras	−1.85	3.09
Gab1	−1.17	−2.71	Nos2	−2.11	−21.53
Grb10	1.44	2.73	Rps6ka1	−1.55	−4.44
Igf1r	−2.00	−2.08	Rras	2.07	2.65
Igf2	−2.37	−4.01	Rras2	−1.58	2.55
Igfbp1	1.01	−2.13	Sos1	−1.09	2.80
Insl1	2.31	1.18
Insl3	4.38	−2.89	Metabolism
Irs2	−1.73	−7.06	Cebpa	1.25	−5.08
Nck1	−1.41	−2.15	Cebpb	1.21	2.48
Ppp1ca	−1.18	−2.83	Fbp1	−2.08	1.10
Ptpn1	−1.05	−3.25	Gpd1	−1.03	−6.32
PI3K Pathway			Gsk3b	1.19	2.59
Akt1	−1.26	−4.65	Ldlr	2.67	3.81
Akt2	−1.16	−3.19	Lep	2.14	1.09
Dusp14	−1.93	−3.11	Pparg	1.26	2.25
G6pc	2.31	1.18	Slc27a4	−1.14	−4.55
Hk2	1.75	2.38
Mtor	−1.38	−3.62	Other Pathways
Pik3ca	−1.21	−2.66	Cfd	1.02	3.10
Pik3r1	−1.49	−3.16	Retn	1.14	−20.16
Pik3r2	−1.16	−3.23	Npy	−1.52	−2.98
Serpine1	3.02	2.66
Ucp1	2.31	1.18

Organoids were cultured for 3d in basal media or supplemented with insulin or IGF. RNA was isolated from collected OSE and reverse transcribed for analysis by cDNA transcription array. Data shown represent fold changes relative to insulin (n=2) after normalization to housekeeping genes.

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