ESR1 and Infertility: ,22,43,44,45 Infertility also occurred in tissue-specific, ERKOs, including uterine epithelial-specific ERKO mice that resulted in implantation failure,46 adipocyte and hypothalamic ERα female knockout mice that exhibited elevated serum E2,47 neuron-specific ERα female knockout mice that exhibited impaired LH secretion and GnRH neuron activation,48 and pituitary-specific female ERKO mice that exhibited a disrupted estrous cycle.49