Abstract
SummaryMaternal malnutrition has important developmental consequences for the foetus. Indeed, adverse fetal ovarian development could have lifelong impact, with potentially reduced ovarian reserve and fertility of the offspring. This study investigated the effect of maternal protein restriction on germ cell and blood vessel development in the fetal sheep ovary. Ewes were fed control (n = 7) or low protein (n = 8) diets (17.0 g vs 8.7 g crude protein/MJ metabolizable energy) from conception to day 65 of gestation (gd65). On gd65, fetal ovaries were subjected to histological and immunohistochemical analysis to quantify germ cells (OCT4, VASA, DAZL), proliferation (Ki67), apoptosis (caspase 3) and vascularisation (CD31). Protein restriction reduced the fetal ovary weight (P < 0.05) but had no effect on fetal weight (P > 0.05). The density of germ cells was unaffected by maternal diet (P > 0.05). In the ovarian cortex, OCT4+ve cells were more abundant than DAZL+ve (P < 0.001) and VASA+ve cells (P < 0.001). The numbers, density and estimated total weight of OCT4, DAZL, and VASA+ve cells within the ovigerous cords were similar in both dietary groups (P > 0.05). Similarly, maternal protein restriction had no effect on germ cell proliferation or apoptotic indices (P > 0.05) and the number, area and perimeter of medullary blood vessels and degree of microvascularisation in the cortex (P > 0.05). In conclusion, maternal protein restriction decreased ovarian weight despite not affecting germ cell developmental progress, proliferation, apoptosis, or ovarian vascularity. This suggests that reduced maternal protein has the potential to regulate ovarian development in the offspring.Lay summaryVariations in a mother’s diet during pregnancy can influence her offspring’s growth and might cause fertility problems in the offspring in later life. We investigated whether reducing the protein fed to sheep during early pregnancy affects their daughters’ ovaries. We then compared our findings to the offspring of sheep on a complete diet. We measured ovary size and estimated the number of germ cells (cells that become eggs) they contained. We used cell markers to assess potential changes in the pattern of germ cell growth, division, and death, and how the ovarian blood supply had developed. We found that protein restriction reduced ovary size. However, the pattern of germ cell development, growth, or death was not altered by poor diet and blood vessels were also unaffected. This suggests that maternal diet can change ovarian development by an unknown mechanism and might reduce future fertility in their offspring.
Highlights
Malnutrition poses a significant health burden, with over 400 million adults suffering from underweight worldwide (WHO 2020a)
Using periodic acid-Schiff staining, the basement membrane was evident in the vascular components and intense in the envelopes that surrounded the egg nests within the ovarian cortex (Fig. 2C and D) and this was present in both dietary groups
This study investigated whether a 50% reduction in maternal gestational protein from conception adversely affected the structure and development of the sheepfetal ovary at gd65 (i.e. 0.44 term in sheep)
Summary
Malnutrition poses a significant health burden, with over 400 million adults suffering from underweight worldwide (WHO 2020a). Since maternal malnutrition is associated with adverse pregnancy and birth outcomes, improved maternal nutrition is acknowledged as a fundamental global health target (WHO 2020b). Gestational dietary restriction has been shown to impact ovarian development in a range of species including pigs (Sui et al 2014b), sheep (Rae et al 2001, Lea et al 2006), cattle (Mossa et al 2013) and rodents (Sloboda et al 2009, Bernal et al 2010) These dietary regimes have included reduced total rations, calories, or protein and have varied widely by the degree, timing and duration of restriction imposed, plus time point of assessment. The provision of inadequate protein in the maternal diet is thought to have a greater impact upon fetal development than a balanced reduction in energy intake, as the deficit in amino acids requires a more substantial shift in maternal metabolism (Dunford et al 2014)
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