Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse

Jun-Jie Wang,Ya-Peng Li,Jing Liu,Shu-Hua Zou,Xiao-Wei Yu,Wei Ge,Massimo De Felici,Wei Shen,Shun-Feng Cheng,Xiao-Feng Sun,Rui-Ying Wu,Jing-Cai Liu

doi:10.1038/s41419-018-0492-2

Abstract

Although it is becoming increasingly evident that maternal starvation during pregnancy can have permanent effects on a range of physiological processes in the offspring, scant information is available about the consequence of such condition for oogenesis and hence for lifetime reproductive success of progeny in mammals. In the present study, we address this topic by starving pregnant mice at the time of ovarian differentiation (12.5 days post coitum (dpc)) for three consecutive days and analyzed the consequence first on the survival of the fetal oocytes and their capability to progress throughout the stages of meiotic prophase I (MPI) and then on the postnatal folliculogenesis of the offspring. The results showed that maternal starvation increased apoptosis in the fetal ovaries, resulting in reduction of the oocyte number. Moreover, MPI progression was slowed down in the surviving oocytes and the expression of DNA repair players in the starved ovaries increased. Transcriptome analysis identified 61 differentially expressed genes between control and starved ovaries, the most part of these being involved in metabolic processes. A significant decrease in the percentage of oocytes enclosed in primordial follicles and the expression of oocyte genes critically involved in folliculogenesis such as Nobox, Lhx8 and Sohlh2 in the 3 days post partum (dpp) starved ovaries were found. Finally, at the time of juvenile period (21 dpp), the number of oocytes and antral follicles resulted significantly lower in the ovaries of the offspring from starved mothers in comparison to controls. Our findings support the notion that maternal starvation can affect ovary development in the offspring that could adversely affect their reproductive success in the adult life.

Highlights

Adequate and correct diet during pregnancy are critical for the health of mother and newborns[1,2,3]
We recently found that starvation at birth impairs germ cell cyst breakdown and increases autophagy and apoptosis in mouse oocytes[21]
We recently found that nutrient deficiency at birth could generate a number of adaptive metabolic and oxidative responses in the ovaries causing increased apoptosis and autophagy in both the somatic cells and oocytes, leading to a delay of germ cell cyst breakdown and follicle assembly[21,28]

Summary

Results and discussion

Many animals alter their reproductive strategies in response to environmental stress. In female Drosophila and Caenorhabditis elegans, starvation activates apoptotic checkpoints and autophagy in oogenesis and reduces the production of mature oocytes[26,27]. In this regard, we recently found that nutrient deficiency at birth could generate a number of adaptive metabolic and oxidative responses in the ovaries causing increased apoptosis and autophagy in both the somatic cells and oocytes, leading to a delay of germ cell cyst breakdown and follicle assembly[21,28]. The body weight of the surviving fetuses was significantly lower in the starved (0.43 ± 0.008 g) compared to control (0.47 ± 0.007 g) groups (Fig. 1f, g, P < 0.01). The Bax/Bcl-2 ratio, evaluated at both the messenger RNA (mRNA) and protein levels, resulted significantly higher

Cholesterol

A Leptotene

Materials and methods

A Control