The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.

The theory of \"Developmental Origins of Health and Disease (DOHaD)\" espouses that environmental exposures to toxicants during critical developmental stages can affect health outcomes in adulthood. Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that can be transferred to developing organisms via the placenta and breast milk as an environmental endocrine disruptor. We herein implemented a cross-fostering model to decipher the contributions of prenatal vs. postnatal exposure to low or high dose DEHP (30 or 500 mg/kg-bw•d) on reproductive outcomes in male offspring and the underlying mechanism of action. Unexpectedly, we observed that postnatal DEHP exposure programmed weight gain in a dose-dependent manner, in-utero exposure to high dose DEHP appeared to constitute a significant factor in the weight loss of male offspring. Moreover, in the low dose group, offspring of control that were suckled by DEHP dams (CC-DE) generated a considerable number of adverse reproductive outcomes compared with the offspring of DEHP that were suckled by control dams (DE-CC), based on histopathologic alterations in the testis, blockage of sex hormone secretion, and transcriptional inhibition of steroid-hormone-related factors in the hypothalamic-pituitary-testicular (HPT) axis. However, DE-CC group affected reproductive dysfunction in male offspring more so than CC-DE in the high dose group. Mechanistically, DEHP contributed to the inhibition of steroidogenesis by perturbing the Wnt/β-catenin-signaling pathway. These studies confirm the sensitivity window in which future reproductive outcomes in offspring are influenced following developmental exposure to DEHP at two different dosages, and reveals a critical role for the Wnt/β-catenin signaling pathway in DEHP-induced male reproductive disorders.

BACKGROUND: Nursing mom can regulate the gut microbiome succession in offspring. However, it remains unclear whether these effects are long-term and what effect it has on the growth performance of piglets. This study aimed to develop a cross-fostering model of piglets and investigate the effect of maternal environment on gut microbiota, even the growth performance of the offspring, and if this effect could be maintained in the long term.
RESULTS: Four groups of piglets were generated as follows (n = 12): Duroc piglets nursed by their birth mom (Dd) or Yorkshire sows (Yd), Yorkshire piglets nursed by Duroc sows (Dy) or their birth mom (Yy). The study found that cross-fostering improved the growth performance of piglets for a long time. The gut microbiota of piglets was mainly determined by the breeds of nursing moms before weaning, and it was more and more influenced by their breeds after weaning, but the influence of birth mom breeds still existed. The linear discriminant analysis (LDA) effect size (LEfSe) analysis and Spearman correlation analysis showed that Sutterella, Butyricimonas and Alistipes, which were affected by nursing mom before weaning, had a strong positive correlation with the growth performance of piglets before weaning. Candidatus_Soleaferrea and Treponema, which were affected by both nursing mom and piglet breed after weaning, were significantly negatively correlated with the growth performance of piglets long after weaning.
CONCLUSIONS: Our results revealed that both the breeds of piglets and their birth moms influence the gut microbiota of piglets for a long time, even after weaning. Additionally, this effect might be related to the growth performance of piglets. © 2022 Society of Chemical Industry.

Previous studies have shown that prenatal stress (PS) can potentially contribute to depression-like behavior in offspring and that this effect may be moderated by cross-fostering. However, the underlying mechanism of this effect remains to be determined. This study aimed to determine the effect of cross-fostering on the expression of EAAT2 and the SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats and to demonstrate functional effects on depression-like behavior. The impacts of cross-fostering were functionally assessed using the sucrose preference test (SPT), the forced swimming test (FST) and the elevated plus maze (EPM). Quantitative real-time PCR was used to determine changes in the expression of EAAT2 and SNAREs mRNA in the hippocampus and the prefrontal cortex of offspring rats. PS offspring rats showed significantly decreased sucrose preference and prolonged immobility time, while cross-fostering effectively increased sucrose preference and shorten the time of immobility. The expression of EAAT2 mRNA in PS offspring rats was markedly reduced, whilst the core mRNA expression of the SNARE complex increased. Our results provide strong evidence demonstrating that cross-fostering can alleviate depression-like behavior and regulate the abnormal expression levels of EAAT2 mRNA and SNARE complex in the hippocampus and the prefrontal cortex of PS offspring rats. Our findings contribute to further understanding of the pathogenesis of PS-induced depression and may help to inform the future development of novel treatment approaches.

The effect of different cross-fostering strategies on the growth performance, stress and immunity of piglets was investigated in this study. In the first experiment, a total of 20 litters (i.e., 20 sows) and 120 piglets were classified into one of six treatments in a 2 × 3 factorial arrangement. The treatments consisted of piglets without or with cross-fostering and different birth weights (low birth weight, LBW; intermediate birth weight, IBW; high birth weight, HBW). The weaning weight (WW) and average daily gain (ADG) of LBW piglets and IBW piglets were not significantly different between the not cross-fostered (NC-F) group and the cross-fostered (C-F) group. There was a higher (p < 0.05) ADG in the control piglets compared with the cross-fostered piglets. This effect on ADG was only seen in the HBW piglets. In the second experiment, six sows with a similar body condition and farrowed on the same day were selected. Three female piglets with a birth weight of 0.6-0.85 kg were selected from each litter as experimental piglets. Eighteen piglets were grouped into three treatments: (1) not cross-fostered (NC-F1), (2) cross-fostered at 36-48 h after birth (C-F1), (3) cross-fostered at day 7 after birth (C-F2). The growth performance of NC-F1 and C-F1 piglets was higher than C-F2 piglets (p < 0.05), and the suckling positions of NC-F1 and C-F1 piglets on days 8, 12, 16 and 20 were more forward than the C-F2 piglets (p < 0.05). Plasma cortisol (COR) concentrations of NC-F1 and C-F1 piglets were lower than C-F2 piglets (p < 0.05). A significant negative correlation was observed between BW at day 21 and plasma COR concentration. In conclusion, cross-fostering within 24 h of birth has adverse influences on the ADG of HBW piglets, while it has no negative effect on the ADG of LBW and IBW piglets. Moreover, for IBW piglets, late cross-fostering (i.e., on day 7 after farrowing) has negative impacts on the growth performance and teat order of piglets, and it increases the cortisol level of piglets.

Nursing mother and breed can differently regulate early-life microbiota succession in pigs. However, it remains unclear whether they affect gastrointestinal microbiota and immune status, which are critical for early-life gut health. Here, an interspecific cross-fostering piglet model was employed by fostering neonatal Yorkshire and Meishan piglets to the same or another breed of sows. Jejunal and colonic microbiotas and mucosal immune parameters were analyzed at postnatal days 14 (preweaning) and 49 (postweaning). Nursing mother affected 10 genera in the colon and 3 minor genera in the jejunum. At day 14, Meishan sow-nursed piglets had lower Streptococcus suis and higher Cloacibacillus counts in the colonic digesta and larger amounts of interleukin 10 and Foxp3-positive cells in the colonic mucosa than did Yorkshire sow-nursed piglets. At day 49, nursing mother had no significant effects on cytokine expression. Breed effects were observed; Meishan piglets had lower relative abundances of Prevotella and lower gene expression of tumor necrosis factor alpha (TNF-α) than those of Yorkshire piglets at days 14 and 49. Collectively, nursing mother mainly affected preweaning colonic microbiota and immune status, while breed effects persisted after weaning. Piglets nursed by Meishan sows had different microbiota compositions and inflammatory cytokine profiles in the colon compared with those of piglets nursed by Yorkshire sows. These results highlight the different role of nursing mother and breed in affecting early gut microenvironment.IMPORTANCE Early-life gut microbiota and immune status are pivotal for postnatal growth. By using an interspecific cross-fostering piglet model, we find that change in nursing mother transiently reshapes preweaning colon microbiota and immune status, while breed shows persistent effects both pre- and postweaning. Piglets nursed by Meishan sows had lower Streptococcus suis counts and higher anti-inflammatory cytokine expression. These results highlight the significance of nursing mother in regulating early-life gut health.

Maximal sustained energy intake (SusEI) appears limited, but the factors imposing the limit are disputed. We studied reproductive performance in two lines of mice selected for high and low food intake (MH and ML, respectively), and known to have large differences in thermal conductance (29% higher in the MH line at 21°C). When these mice raised their natural litters, their metabolisable energy intake significantly increased over the first 13 days of lactation and then reached a plateau. At peak lactation, MH mice assimilated on average 45.3% more energy than ML mice (222.9±7.1 and 153.4±12.5 kJ day(-1), N=49 and 24, respectively). Moreover, MH mice exported on average 62.3 kJ day(-1) more energy as milk than ML mice (118.9±5.3 and 56.6±5.4 kJ day(-1), N=subset of 32 and 21, respectively). The elevated milk production of MH mice enabled them to wean litters (65.2±2.1 g) that were on average 50.2% heavier than litters produced by ML mothers (43.4±3.0 g), and pups that were on average 27.2% heavier (9.9±0.2 and 7.8±0.2 g, respectively). Lactating mice in both lines had significantly longer and heavier guts compared with non-reproductive mice. However, inconsistent with the \'central limit hypothesis\', the ML mice had significantly longer and heavier intestines than MH mice. An experiment where the mice raised litters of the opposing line demonstrated that lactation performance was not limited by the growth capacity of offspring. Our findings are consistent with the idea that the SusEI at peak lactation is constrained by the capacity of the mothers to dissipate body heat.