Research Article: Gestational diabetes promotes germ cell cCyst breakdown and primordial follicle formation in newborn mice via the AKT signaling pathway

Date Published: April 11, 2019

Publisher: Public Library of Science

Author(s): Junjun Xu, Jiaojiao Huang, Qingjie Pan, Miao Du, Zhen Li, Huansheng Dong, Meijia Zhang.

http://doi.org/10.1371/journal.pone.0215007

Abstract

Type 1 diabetes (T1D) is a common disease in which pancreatic β cells are impaired due to auto-immunity, pregnancy in women with it is associated with increased risk of neonatal morbidity, mortality. However, the effects of gestational diabetes on the reproduction of newborn offspring are still poorly understood. Here, we determined the cyst breakdown and primordial follicle formation in neonatal offspring born by streptozotocin (STZ)-induced diabetic or non-diabetic female mice, and found that the germ cell cyst breakdown was promoted in neonatal offspring of STZ -induced diabetic mice at postnatal Day 1, which sequentially accelerated the primordial follicle formation. Further investigation revealed that, the expression level of PI3K and p-AKT were significantly increased in ovaries of offspring born by T1D mice. These results indicated that STZ -induced gestational diabetes promotes germ cell cyst breakdown and primordial follicle formation by regulating the PI3K/AKT signaling pathway in the newborn offspring. In addition, this effect can be rescued by an insulin supplement. Taken together, our results uncover the intergenerational effects of gestational diabetes on neonatal offspring folliculogenesis, and provide an experimental model for treating gestational diabetes and its complications in neonatal offspring.

Partial Text

Type 1 diabetes (T1D) is a common disease in which pancreatic β cells are impaired due to auto-immunity [1], accounts for 5–10% of all diabetes, and typically occurs in children and adolescents especially in developed countries [2]. T1D has recently been on the rise globally. Nearly half of pregnant women are either overweight or obese at conception [3]. These adverse conditions significantly increase the risk of gestational diabetes in pregnant women [4]. The occurrence and development of pregnancy complications are closely related to the blood glucose levels in women with T1D [5]. Pregnant women with T1D display a higher incidence of reproductive problems, such as infertility, miscarriage, and their offspring are more likely to develop congenital malformations and show a higher rate of fetal death than those of nondiabetic mothers [6–8].

In this study, we provided new insights into the effect of gestational diabetes on the early stages of mammalian folliculogenesis. Previous studies have demonstrated that maternal diabetes adversely affects pregnancy outcomes, such as infertility, miscarriage, offspring with congenital malformations and fetal death [6]. Our results which are consistent with the previous studies in addition demonstrate that gestational diabetes adversely affects the development of the newborn offspring. The average number of offspring was reduced, and the average body length was significantly larger in the STZ-treated group compared to the control. Moreover, we found that offspring glucose and serum insulin level were significantly higher, but returned to normal levels in two weeks. The glucose from pregnant diabetic mice can be transferred into the offspring, resulting in the increase of offspring glucose level. The high glucose level in offspring may stimulate the growth of the pancreas, which in turn generates more insulin to decrease glucose level.

Our data supported that the PI3K/AKT signaling pathway regulates the early stage of folliculogenesis, resulting in promoting cyst breakdown and primordial follicle formation in newborn mice caused by STZ-induced gestational diabetes. These delirious effects can be rescued by insulin supplement. Our study suggested therapeutic potential of insulin to treat developmental defects in newborns suffering from gestational diabetes.

 

Source:

http://doi.org/10.1371/journal.pone.0215007

 

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