Gestational zinc deficiency impairs brain astrogliogenesis in rats through multistep alterations of the JAK/STAT3 signaling pathway.

We previously showed that zinc (Zn) deficiency affects the STAT3 signaling pathway in part through redox-regulated mechanisms. Given that STAT3 is central to the process of astrogliogenesis, this study investigated the consequences of maternal marginal Zn deficiency on the developmental timing and key mechanisms of STAT3 activation, and its consequences on astrogliogenesis in the offspring. This work characterized the temporal profile of cortical STAT3 activation from the mid embryonic stage up to young adulthood in the offspring from dams fed a marginal Zn deficient diet (MZD) throughout gestation and until postnatal day (P) 2. All rats were fed a Zn sufficient diet (control) from P2 until P56. Maternal zinc deficiency disrupted cortical STAT3 activation at E19 and P2. This was accompanied by altered activation of JAK2 kinase due to changes in PTP1B phosphatase activity. The underlying mechanisms mediating the adverse impact of a decreased Zn availability on STAT3 activation in the offspring brain include: (i) impaired PTP1B degradation via the ubiquitin/proteasome pathway; (ii) tubulin oxidation, associated decreased interactions with STAT3 and consequent impaired nuclear translocation; and (iii) decreased nuclear STAT3 acetylation. Zn deficiency-associated decreased STAT3 activation adversely impacted astrogliogenesis, leading to a lower astrocyte number in the early postnatal and adult brain cortex. Thus, a decreased availability of Zn during early development can have a major and irreversible adverse effect on astrogliogenesis, in part via multistep alterations in the STAT3 pathway.

Associations of Maternal Weight Status Before, During, and After Pregnancy with Inflammatory Markers in Breast Milk.

OBJECTIVE: The goal of this study was to examine the associations of maternal weight status before, during, and after pregnancy with breast milk C-reactive protein (CRP) and interleukin 6 (IL-6), two bioactive markers of inflammation, measured at 1 and 3 months post partum. METHODS: Participants were 134 exclusively breastfeeding mother-infant dyads taking part in the Mothers and Infants Linked for Health (MILK) study, who provided breast milk samples. Pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) were assessed by chart abstraction; postpartum weight loss was measured at the 1- and 3-month study visits. Linear regression was used to examine the associations of maternal weight status with repeated measures of breast milk CRP and IL-6 at 1 and 3 months, after adjustment for potential confounders. RESULTS: Pre-pregnancy BMI and excessive GWG, but not total GWG or postpartum weight loss, were independently associated with breast milk CRP after adjustment (ß = 0.49, P < 0.001 and ß = 0.51, P = 0.011, respectively). No associations were observed for IL-6. CONCLUSIONS: High pre-pregnancy BMI and excessive GWG are associated with elevated levels of breast milk CRP. The consequences of infants receiving varying concentrations of breast milk inflammatory markers are unknown; however, it is speculated that there are implications for the intergenerational transmission of disease risk.