Maternal protein restriction affects fetal ovary development in sheep

Abstract

Maternal malnutrition has important developmental consequences for the fetus. 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 (17.0g versus 8.7g crude protein.MJ-1 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 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 potential to regulate ovarian development in the offspring.

Potential factors result in diminished ovarian reserve: a comprehensive review

“…Studies in animal models have suggested that maternal undernutrition results in a smaller ovary in the fetus and an increased testosterone concentration [ 83 , 84 ]. In addition, protein restriction in mothers has been shown to impair germ cell and blood vessel development in the fetal ovaries of sheep and the number of primordial follicles in mice [ 85 , 86 ]. The second study also found that primordial follicles were significantly depleted by 37% at PN21 and 51% at 24-week mice with statistical significance.…”

Prostaglandins as local regulators of ovarian physiology in ruminants

“…In recent years, the important role of locally produced mediators (paracrine actions) such as growth factors, cytokines and various peptides in modulating folliculogenesis and ovulation has been established (Hunter et al, 2004; Mishra et al, 2017; Nwachukwu et al, 2023; Rawlings et al, 2003; Scaramuzzi et al, 2011; Schams et al, 2009). During the ovulation process, the LH peak stimulates molecular mechanisms and different locally produced factors, which support the effect of gonadotropins in the completion of the ovulation process and the formation of the CL (Berisha & Schams, 2005; Juengel et al, 2021).…”

“…Growth factors like IGF system members can stimulate either the proliferation or the differentiation and differentiated functions of granulosa cells, depending on the follicle's development stage (Scaramuzzi et al, 2011). While the last publication of Nwachukwu et al (2023) highlights the importance of IGF signalling in regulating luteal angiogenesis and function in the cow. In addition, some research groups have demonstrated the importance of adipokines system members like adiponectin, resistin, chemerin, visfatin and apelin in the regulation of bovine ovarian function (Juengel et al, 2021; Kurowska et al, 2021; Thaqi et al, 2023).…”

“…In addition to endocrine factors, the optimal luteal function also depends on the activity of many paracrine factors locally produced in the CL. Of the numerous family members that have been identified, the most important appear to be the group of growth factors, peptides, steroids and prostaglandins that stimulate cell growth, differentiation and survival of luteal cells (Gabler et al, 2004; Nwachukwu et al, 2023; Richards et al, 2002). These factors are not only necessary for the establishment of the capillary system (angiogenesis) in the tissues of the CL, but they are also important mediators for the stimulation of progesterone and other hormones that enable the optimal functioning of the CL during the oestrous cycle and pregnancy (Kobayashi et al, 2001; Levy et al, 2000; Neuvians et al, 2003a; Pate, 1988).…”

Developmental Programming of Fertility in Cattle—Is It a Cause for Concern?

“…Another study reported that primordial follicles from fetal sheep ovaries collected on day 135 of gestation following a 60% nutrient restriction from day 50 of gestation onwards had a decreased cellular proliferation rate compared with those from fetal ovaries of adequately fed ewes [ 89 ]. Nwachukwu et al [ 90 ] fed ewes low protein diets for the first half of gestation. Ovarian weight in the fetuses was again reduced compared with the controls, but in this case there were no apparent differences in germ cell development at mid gestation.…”