Figure 8

Hypothetic model for Umodl1 function on ovarian ageing. This schematic diagram summarizes the reproductive defects caused by Umodl1 overexpression. Meanwhile, a putative stimulatory interplay of FSH/LH and Umodl1 on accelerating ovarian ageing is proposed based on the close correlation between the ovarian defects with the abnormal levels of circulating FSH in the mutants. At early reproductive age, the ‘defective’ ovaries intrinsic to Umodl1-overexpression send faulty signals to the hypothalamus-pituitary, thus resulting in elevated circulating FSH. Once the plasma FSH/LH reach the threshold levels as the ovarian deterioration proceeds, FSH/LH may act directly or indirectly on the over-expressed Umodl1. Consequently, the signaling pathway(s) mediated by Umodl1 is further amplified, imposing detrimental influences on the health of oocytes themselves. Fragmented oocytes fail to correctly instruct the proliferation and differentiation of GCs, resulting in increased apoptosis and cell-fate alteration. Collectively, these adverse impacts lead to the eventual collapse of ovarian function.