MAPK signaling is a master regulator of oogenesis during reproductive aging.

The success of human reproduction is highly dependent on maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte quality due to meiotic segregations failures, a major contributor to aneuploidy. This results in fewer pregnancies and increased occurrence of birth defects. C. elegans is an excellent model to study how oocyte quality is regulated during aging. Unlike mammals, in the adult worm all oogonial stages are present, from the stem cells to the mature oocyte. Moreover, oocytes in the worm show, after several days of arrest, defects similar to those found in human oocytes arrested for decades. However, factors that specifically control germline aging remain to be deciphered. Here we show that functions involving oogenesis progression and meiotic chromosome dynamics are altered with age. Germlines of older animals presents (1)impaired meiotic progression as shown by nuclei that progressed from a premeiotic appearance to an early pachytene appearance, (2)defects in double-strand break repair as well as in crossover formation and (3)early disassembly of the synaptonemal complex. Our previous results pointed toward the MAPK signaling pathway as a master regulator of oogenesis. Indeed, we observed a deregulation of this pathway in the germline of aged worms as indicated by a change in the oogonial stages in which the MAPK terminal member ERK/MPK1 is phosphorylated. We further demonstrate that reducing MAPK signaling at specific stages delays reproductive aging by maintaining oocyte and germline quality. Our study opens possibilities for improving oocyte quality by pharmacologically manipulating MAPK signaling.