In contrast, 49 downregulated genes (Extended Data Fig. 2j) included several with established roles in ovarian function and premature aging, such as Lars2 (mutations cause Perrault syndrome with ovarian failure51), Gpr3 (loss leads to premature ovarian aging and early meiotic resumption in mice52), Lamc1 (associated with premature ovarian failure in human cohorts53), and Drosha (polymorphisms associated with idiopathic POI risk54). Here, LAMC1 is linked to primary ovarian failure.