Oxidative Stress Experienced during Early Development Influences the Offspring Phenotype.

AbstractOxidative stress (OS) experienced early in life can affect an individual's phenotype. However, its consequences for the next generation remain largely unexplored. We manipulated the OS level endured by zebra finches (Taeniopygia guttata) during their development by transitorily inhibiting the synthesis of the key antioxidant glutathione ("early-high-OS"). The offspring of these birds and control parents were cross fostered at hatching to enlarge or reduce its brood size. Independent of parents' early-life OS levels, the chicks raised in enlarged broods showed lower erythrocyte glutathione levels, revealing glutathione sensitivity to environmental conditions. Control biological mothers produced females, not males, that attained a higher body mass when raised in a benign environment (i.e., the reduced brood). In contrast, biological mothers exposed to early-life OS produced heavier males, not females, when allocated in reduced broods. Early-life OS also affected the parental rearing capacity because 12-day-old nestlings raised by a foster pair with both early-high-OS members grew shorter legs (tarsus) than chicks from other groups. The results indicate that environmental conditions during development can affect early glutathione levels, which may in turn influence the next generation through both pre- and postnatal parental effects. The results also demonstrate that early-life OS can constrain the offspring phenotype.

Adaptive downregulation of pheomelanin-related Slc7a11 gene expression by environmentally induced oxidative stress.

Pheomelanin is a sulphur-containing yellow-to-reddish pigment whose synthesis consumes the main intracellular antioxidant (glutathione; GSH) and its precursor cysteine. Cysteine used for pheomelanogenesis cannot be used for antioxidant protection. We tested whether the expression of Slc7a11, the gene regulating the transport of cysteine to melanocytes for pheomelanogenesis, is environmentally influenced when cysteine/GSH are most required for antioxidant protection. We found that zebra finches Taeniopygia guttata developing pheomelanin-pigmented feathers during a 12-day exposure to the pro-oxidant diquat dibromide downregulated the expression of Slc7a11 in feather melanocytes, but not the expression of other genes that affect pheomelanogenesis by mechanisms different from cysteine transport such as MC1R and Slc45a2. Accordingly, diquat-treated birds did not suffer increased oxidative stress. This indicates that some animals have evolved an adaptive epigenetic lability that avoids damage derived from pheomelanogenesis. This mechanism should be explored in human Slc7a11 to help combat some cancer types related to cysteine consumption.

The level of an intracellular antioxidant during development determines the adult phenotype in a bird species: a potential organizer role for glutathione.

Life-history traits are often involved in trade-offs whose outcome would depend on the availability of resources but also on the state of specific molecular signals. Early conditions can influence trade-offs and program the phenotype throughout the lifetime, with oxidative stress likely involved in many taxa. Here we address the potential regulatory role of a single intracellular antioxidant in life-history trade-offs. Blood glutathione levels were reduced in a large sample of birds (zebra finch Taeniopygia guttata) during development using the synthesis inhibitor buthionine sulfoximine (BSO). Results revealed several modifications in the adult phenotype. BSO-treated nestlings showed lower glutathione and plasma antioxidant levels. In adulthood, BSO birds endured greater oxidative damage in erythrocytes but stronger expression of a sexual signal. Moreover, adult BSO females also showed weaker resistance to oxidative stress but were heavier and showed better body condition. Results suggest that low glutathione values during growth favor the investment in traits that should improve fitness returns, probably in the form of early reproduction. Higher oxidative stress in adulthood may be endured if this cost is paid later in life. Either the presence of specific signaling mechanisms or the indirect effect of increased oxidative stress can explain our findings.