Maternal Undernutrition Significantly Impacts Ovarian Follicle Number and Increases Ovarian Oxidative Stress in Adult Rat Offspring

Abstract

BackgroundWe have shown recently that maternal undernutrition (UN) advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress.Methodology/Principal FindingsOur study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone.ConclusionsWe propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of maternal UN potentially contributing to premature ovarian ageing in offspring.

Development of mammalian ovary

“…In cattle, ovaries from animals born following a gestational nutrition challenge have low numbers of antral follicles, low plasma AMH concentrations, and a low ovarian reserve (Mossa et al 2009). Similar results have been reported in rats (Bernal et al 2010), while in sheep there appears to be no difference in ovarian reserve, but fewer growing follicles (Rae et al 2001). The mechanisms underlying the development of these post-natal symptoms have been most fully studied in sheep, where it has been proposed that a delay in meiotic maturation is largely responsible (Rae et al 2001, Lea et al 2006.…”

Accelerated aging of reproductive capacity in male rat offspring of protein-restricted mothers is associated with increased testicular and sperm oxidative stress

“…In addition, the presence of an array of testicular antioxidant enzymes and free radical scavengers help protect this organ from the impact of OS (Aitken and Roman 2008). In this regard, several perinatal conditions such as maternal malnutrition, maternal obesity, or excessive exposure to glucocorticoids (a common fetal response to developmental programming challenges) (Zambrano et al 2014b) increase OS (Bernal et al 2010;Mutsaers and Tofighi 2012;Zambrano and Nathanielsz 2013). Tarry-Adkins et al have reported that maternal undernutrition using a lowprotein diet (8 %), similar to the one we used, is associated with increased OS and an impaired antioxidant defense capacity in the pancreas of male rat offspring at 3 and 15 months of age (Tarry-Adkins et al 2010).…”

Establishment of a Mouse Model of Premature Ovarian Failure Using Consecutive Superovulation

“…They were serially sectioned (6 μm), mounted on glass slides, and stained with H&E. All ovarian follicles were counted according to a previous study [29, 30]. In brief, every fifth ovary section was observed under a microscope.…”