Maternal undernutrition during pregnancy and lactation increases transcription factors, ETV5 and GDNF, and alters regulation of apoptosis and heat shock proteins in the testis of adult offspring in the rat

Abstract

We tested whether changes in Sertoli cell transcription factors and germ cell heat shock proteins (HSPs) are linked to the effects of maternal undernutrition on male offspring fertility. Rats were fed ad libitum with a standard diet (CONTROL) throughout pregnancy and lactation or with 50% of CONTROL intake throughout pregnancy (UNP) or lactation (UNL) or both periods (UNPL). After postnatal Day 21, 10 male pups per group were fed a standard diet ad libitum until postnatal Day 160 when testes were processed for histological, mRNA and immunohistochemical analyses. Compared with CONTROL: caspase-3 was increased in UNP and UNPL (P=0.001); Bax was increased in UNL (P=0.002); Bcl-2 (P<0.0001) was increased in all underfed groups; glial cell line-derived neurotrophic factor (P=0.002) was increased in UNP and UNL; E twenty-six transformation variant gene 5 and HSP70 were increased, and HSP90 was diminished in all underfed groups (P<0.0001). It appears that maternal undernutrition during pregnancy and lactation disrupts the balance between proliferation and apoptosis in germ cells, increasing germ cell production and perhaps exceeding the support capacity of the Sertoli cells. Moreover, fertility could be further compromised by changes in meiosis and spermiogenesis mediated by germ cell HSP90 and HSP70.

Maternal high-fat diet during pregnancy and lactation affects factors that regulate cell proliferation and apoptosis in the testis of adult progeny

“…It is of interest to compare the outcomes of the present study with those from our recent work on the effects of maternal undernutrition during pregnancy or lactation. Notably, undernutrition evoked an opposite effect by increasing IGF-I production, whereas both dietary treatments evoked a decrease in GDNF (Pedrana et al 2020(Pedrana et al , 2021.…”

“…This apparent contradiction can be explained by the well-established post-transcriptional modification of Bcl-2 protein (Greenbaum et al 2003;Ramazi and Zahiri 2021). Indeed, we had previously shown that immunoexpression of Bcl-2 protein caspase-3 increase in parallel (Pedrana et al 2021), consistent with Bcl-2 preventing apoptosis by blocking the release of cytochrome C from the mitochondria. In turn, pores induced by Bax permit the release of mitochondrial cytochrome C into the cytosol, subsequently activating the caspase cascade that leads to apoptosis (Singh et al 2019).…”

“…An adverse maternal environment during fetal life would also be expected to alter germ cell production and thus compromise the fertility of the next generation (Vautier and Cadaret 2022). Indeed, recent studies in the rat by our group (Pedrana et al 2020(Pedrana et al , 2021 have shown that maternal undernutrition significantly impacts on several molecular factors that control testis function in developing male offspring.…”

Frontiers in sheep reproduction - making use of natural responses to environmental challenges to manage productivity

“…The proliferation of Sertoli cells is an obvious target for DOHAD because Sertoli cell number is fixed at puberty, and adult fertility is largely determined by the ratio of Sertoli cells to germ cells. Indeed, as shown by studies in rats, maternal undernutrition changes the balance between cell proliferation and apoptosis in the developing testes, an essential aspect of the regulation of spermatogenesis (Pedrana et al, 2021).…”

Balancing nutrition for successful reproduction in ruminants

“…4 It appears that maternal undernutrition during pregnancy and lactation impairs the balance between germ cell proliferation and cell death in rats, and this equilibrium is critical for spermatogenesis. 10 Maternal low protein diet also delays the time of puberty in rats and leads to reduced sperm count. [11][12][13] These findings clearly demonstrated the negative impact of maternal undernutrition on male reproduction.…”