In light of the above findings, we decided to evaluate whether and how the estradiol alone or in combinations with GPER agonist and GPER and PPARs antagonists affect the protein expression of tumorigenic and angiogenic factors, TGF-β, COX-2, HIF-1α, and VEGF, in both ex vivo and in vitro models such as mouse testis explants and mouse tumor Leydig cells. The gene discussed is HIF1A; the disease is neoplasm.