Maternal circadian disruption before pregnancy impairs the ovarian function of female offspring in mice

Abstract

Circadian disturbance brought on by shift employment, nighttime light pollution, and other factors is quite prevalent in contemporary culture. However, the effect of maternal circadian disruption before pregnancy on the reproduction of offspring in mice requires further research. Herein, we exposed female ICR mice to constant light to establish a model of preconceptional circadian disruption and then checked the ovarian function of female offspring (named the CLE group below). Our results revealed obesity, abnormal lipid metabolism and earlier puberty onset in the CLE group. Additionally, impaired ovarian follicle development, oocyte quality and preimplantation embryo development were shown in the CLE group. Moreover, the expression levels of Gnrh1 in the hypothalamus and Cyp17a1, Bmper, Bdnf and Lyve1 in ovaries, as well as circadian clock genes, including Clock, Cry1, Nr1d2 and Per2, were significantly downregulated in the CLE group. Mechanistically, immune responses, including the interleukin-17 (IL-17) signalling pathway, cytokine–cytokine receptor interaction and the chemokine signalling pathway, were altered in the CLE group, which may be responsible for the damaged ovarian function.