Pregnancy at Advanced Maternal Age Affects Behavior and Hippocampal Gene Expression in Mouse Offspring

Abstract

There is growing evidence that advanced maternal age is a risk factor for neurological and neuropsychiatric disorders in offspring. However, it remains unclear whether the altered brain programming induced by advanced maternal age is mediated by pre- or postnatal factors. Here, a mouse model was used to investigate whether pregnancy at advanced age may provoke behavioral and brain gene expression changes in offspring. Swiss Albino mice conceived by 3-month-old males and either 15–18-month-old (n = 11) or 3-month-old control females (n = 5), were delivered by cesarean section, fostered after birth by 3-month-old dams and subjected to a battery of behavioral tests. Furthermore, genome-wide mRNA expression was analyzed in the hippocampi of 4-month-old males offspring using microarrays. Offspring conceived by old mothers exhibited increased ultrasound vocalization activity during separation from the foster mother, increased anxiety-like behaviors in adult life, and altered patterns of hippocampal gene expression, compared to controls. These effects were not reversed by the postnatal maternal care provided by the young foster mothers, suggesting that the altered brain programming is already established at birth, consistent with prenatal effects related to maternal aging.

Preconceptional Resveratrol Supplementation Partially Counteracts Age-Related Reproductive Complications in C57BL/6J Female Mice

“…Previous studies indicated that C57 female mice display a reproductive decline starting at 6-8 months, which results in decreased pregnancy rate, increased fetal resorption and diminished litter size [27]. Such effects of ageing were also observed by us in an outbred strain [28] and in inbred C57 and BTBR T+ Itpr3tf/J mice [29]. In the present study, one-year-old females supplemented with RES were mated faster than controls.…”

Maternal Age at Childbirth and Parental Reports of Attention-Deficit/Hyperactivity Disorder and Learning Disability, Ages 4 to 15 Years

“…Some existing mechanistic studies have con rmed that the spatial learning capacity of mice at 32-35 weeks is lower than that of mice at 9-12 weeks, which may be related to the decrease in the expression of vitamin D receptor (VDR) in the early embryogenesis process [47]. In addition, compared with 3-month-old mice, 15-18-month-old mice showed anxiety-like behavior, and the gene expression pattern of the hippocampus also changed [48]. We also speculated that late production age may be related to the egg quality [49].…”

Delayed parenthood and its influence on offspring health: what have we learned from the mouse model

“…Decline of female reproductive functions over time is characterized by a decrease in oocyte reservoir, low oocyte quality and high risk of pregnancy loss or complications, as widely described in several mammalian species [31][32][33][34][35][36][37][38][39][40]. Mouse models showed that aged females (> 10 months old) are able to produce progeny, however pregnancies are characterized by smaller litter size and increased rate of complications/pregnancy lost when compared to pregnancy outcome in young females [32][33][34].…”

“…Regarding post implantation development, an association between AMA and increased risk of pregnancy complications (such as pregnancy loss and fetal malformations, impaired placental development, difficulties in spontaneous parturition, and low birth weight) has been widely described [33,34,[38][39][40]. For example, Woods et al [40] showed that at least two-thirds of fetuses conceived by aged mothers were characterized by fetal growth retardation, cardiac edema, brain and neural tube defects, as well as vascular defects (e.g., dilated dorsal aorta and/or major brain artery).…”