Functional roles of m⁶A modification in reproductive physiology. (IMAGE)
Caption
Successful pregnancy requires coordinated physiological processes, with m⁶A participating in critical stages: i) Folliculogenesis: m⁶A dynamically regulates oocyte-granulosa cell crosstalk during follicular maturation from primordial follicles to metaphase II (MII) oocytes, mediated by key regulators including METTL3, METTL14, KIAA1429, FTO, YTHDC1, YTHDC2, and IGF2BP1. ii) Embryogenesis: Following fertilization, m⁶A governs epigenetic modulation of zygotic development from the 2-cell stage through blastocyst formation. iii) Embryo implantation: Endometrial receptivity, a pivotal determinant of implantation success, is enhanced by m⁶A-mediated homeostatic control of hormonal metabolic signaling, involving METTL3, METTL14, METTL16, WTAP, and IGF2BP2. iv) Immune microenvironment: Embryo-derived immunomodulatory factors recruit immune cells to coordinate developmental processes. m⁶A regulators such as METTL3, METTL14, IGF2BP2, ALKBH5, and YTHDF2 modulate T cell/NK cell activities during immune adaptation. METTL3/14/16, methyltransferase 3/14/16; ALKBH5, ALKB homologue 5; FTO, fat mass and obesity-associated protein; YTHDC1/2, YTH domain containing 1/2; WTAP, Wilms tumor 1-associated protein; KIAA1429, also called VIRMA, vir-Like m⁶A methyltransferase associated, VIRILIZER; IGF2BP1/2, insulin-like growth factor-2 mRNA-binding protein 1/2; YTHDF2, YTH domain family 2; NK, natural killer.
Credit
Jie Ding, Yalun He, Yangshuo Li, Shuai Sun, Wen Cheng, Jiami Huang, Chaoqin Yu
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CC BY-NC-ND