Competition for Materno-Fetal Resource Partitioning in a Rabbit Model of Undernourished Pregnancy

Abstract

The major goal of animal production is to obtain abundant and healthy meat for consumers. Maternal food restriction (MFR) is often applied in farms to reduce production costs. However, the suitability of MFR in livestock animals is questionable, as this management may compromise maternal fitness due to a severe negative energetic balance and can induce Intrauterine Growth Restriction (IUGR) and prenatal programming in the offspring. Here, we sought to determine, using pregnant rabbits, the consequences of MFR on maternal endocrine and metabolic status and conceptus development. Pregnant dams were distributed into three groups: CONTROL (ad libitum feeding throughout the entire pregnancy; mean pregnancy length being around 31 days), UNDERFED (50% MFR during the entire pregnancy) and EARLY-UNDERFED (50% MFR only during the preimplantation period, Days 0–7). Maternal leptin concentrations and glycemic and lipid profiles were determined throughout pregnancy, whilst conceptus development was assessed ex-vivo at Day 28. Placental parameters were determined by macroscopic and histological evaluations and apoptotic assessments (TUNEL and Caspase-3). The main results of the study showed that, despite MFR altered maternal plasma lipid concentration (P<0.05), there were no effects on maternal bodyweight, plasma leptin concentration or glycemic profile. Fetal crown-rump lengths were reduced in both undernourished groups (P<0.001), but a significant reduction in fetal weight was only observed in the UNDERFED group (P<0.001). Growth in both undernourished groups was asymmetrical, with reduced liver weight (P<0.001) and significantly increased brain: fetal weight-ratio (P<0.001) and brain: liver weight-ratio (P<0.001) when compared to the CONTROL group. A significant reduction in placental weight was only observed in the UNDERFED group (P<0.001), despite both undernourished groups showing higher apoptotic rates at decidua and labyrinth zone (P<0.05) than the CONTROL group. Thus, these groups evidenced signs of placental degeneration, necrosis and stromal collapse. In summary, MFR may encourage the mother to make strategic decisions to safeguard her metabolic status and fitness at the expense of growth reduction in the litter, resulting in enhanced apoptotic and pathological processes at placental level and IUGR.

Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model

“…Feed intake of underfed mothers increased during the last week of gestation, when feeding was re-established, according to Daoud et al [40] and Lopez Tello et al [4]. Probably, this compensatory feed intake during the last third of gestation was enough to promote recuperation of the maternal LBW and energetic body reserves, as shown in estimated body composition results.…”

“…Histological changes in placenta of undernourished females were found. Fewer vessels, with hyalinized and sclerotic walls, and lesser supporting stroma as well as necrosis were observed [4]. In addition, Fortun et al [49] also appreciated lower weight rates when does were restricted to 75% of their maintenance requirements during the entire pregnancy, but they observed a similar rate of embryo viability.…”

“…According to the Developmental Origins of Health and Disease hypothesis, maternal food restriction during the intrauterine developmental period can affect long-term metabolic health of offspring due to alterations of organ structures and epigenetic programming [1,2] Maternal malnutrition influences on placenta development and efficiency, and subsequently, the availability of nutrients for the fetuses can be compromised [3,4]. In addition, fetal energy homeostasis [5] and metabolism [6,7] are reprogrammed and, as a result, the fetus re-distributes the limited fuel in order to ensure the development of vital organs (such as the brain and heart) by decreasing energy consumption in secondary organs (such as the liver, gut, etc.)…”

Models of Intrauterine growth restriction and fetal programming in rabbits

“…In rabbits, maternal food restriction can also influence offspring outcomes, although the specific change depends on the timing, severity of the deprivation, and the resultant impacts on maternal body weight gain (summarized in Table ). In particular, ≤50% reduction in daily feed intake from early in gestation typically limits rabbit doe gestational weight gain and results in miscarriage, asymmetric IUGR, and fetal malformations, such as reduced bone ossification (Cappon, Fleeman, Chapin, & Hurtt, ; Clark et al, ; Flake, Villa, Adzick, & Harrison, ; López‐Tello et al, ; López‐Tello, Arias‐Álvarez, Jiménez‐Martínez, Barbero‐Fernández et al, ; López‐Tello, Arias‐Álvarez, Jimenez‐Martinez, Garcia‐Garciaet al, ; Matsuzawa, Nakata, Goto, & Tsushima, ; Petrere, ; Symeon et al, ). Offspring bone development is also impaired by malnutrition in other animal species, including rats that are exposed to a maternal low protein diet during gestation (Hanson & Gluckman, ; Hastings‐Roberts & Zeman, ; Wood, Stenson, & Embleton, ).…”

“…In response to a 50% reduction in maternal food intake, placental weight may be decreased or unchanged, depending on the timing of exposure in pregnant rabbits (from before or after implantation) (López‐Tello, Arias‐Álvarez, Jimenez‐Martinez, Garcia‐Garciaet al, ). Although, regardless of whether there is a change in placental weight, 50% maternal undernutrition compromises labyrinthine zone structure, with increased fibrosis, apoptosis and stromal collapse compared with control rabbit does (López‐Tello, Arias‐Álvarez, Jiménez‐Martínez, Barbero‐Fernández et al, ; López‐Tello, Arias‐Álvarez, Jimenez‐Martinez, Garcia‐Garciaet al, ).…”