Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

AIM: Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. MAIN METHODS: Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. KEY FINDINGS: Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. SIGNIFICANCE: A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.

Hepatic lipid metabolism in adult rats using early weaning models: sex-related differences.

Non-pharmacological early weaning (NPEW) induces liver damage in male progeny at adulthood; however, pharmacological early weaning (PEW) does not cause this dysfunction. To elucidate this difference in liver dysfunction between these two models and determine the phenotype of female offspring, de novo lipogenesis, ß-oxidation, very low-density lipoprotein (VLDL) export, and gluconeogenesis in both sexes were investigated in the adult Wistar rats that were weaned after a normal period of lactation (control group) or early weaned either by restriction of access to the dams' teats (NPEW group) or by reduction of dams' milk production with bromocriptine (PEW group). The offspring received standard diet from weaning to euthanasia (PN180). NPEW males had higher plasma triglycerides and TyG index, liver triglycerides, and cholesterol by de novo lipogenesis, which leads to intracellular lipids accumulation. As expected, hepatic morphology was preserved in PEW males, but they showed increased liver triglycerides. The only molecular difference between PEW and NPEW males was in acetyl-CoA carboxylase-1 (ACC-1) and stearoyl-CoA desaturase-1 (SCD-1), which were lower in PEW animals. Both early weaning (EW) females had no changes in liver cholesterol and triglyceride contents, and the hepatic cytoarchitecture was preserved. The expression of microsomal triglyceride transfer protein was increased in both the female EW groups, which could constitute a protective factor. The changes in hepatic lipid metabolism in EW offspring were less marked in females. EW impacted in the hepatic cytoarchitecture only in NPEW males, which showed higher ACC-1 and SCD-1 when compared to the PEW group. As these enzymes are lipogenic, it could explain a worsened liver function in NPEW males.

Short and long-term effects of bisphenol S (BPS) exposure during pregnancy and lactation on plasma lipids, hormones, and behavior in rats.

Bisphenol S (BPS) has replaced bisphenol A (BPA), a known non-persistent endocrine disrupting chemical, in several products. Considering that little is known regarding BPS effects, especially during critical windows of ontogenetic development, and that BPA, which is quite similar to BPS, is know to be transferred to the offspring via the placenta and milk, in the present study we investigated the behavioral, biochemical and endocrine profiles of Wistar rats born from dams that were BPS-exposed [groups: BPS10 (10 µg/kg/day), BPS50 (50 µg/kg/day)] during pregnancy and lactation. Due to the non-monotonic dose-response effect of bisphenol, the data of both BPS groups were directly compared with those of the controls, not to each other. Males and females were analyzed separately. At weaning, male BPS50 offspring had hypotriglyceridemia and hyperthyroxinemia, whereas BPS50 females showed higher 25(OH)D levels. At adulthood, BPS offspring of both sexes had lower food intake. BPS males showed lower visceral adiposity. BPS50 females had smaller fat droplets in brown adipocytes. BPS males showed higher anxiety and higher locomotor activity, while BPS10 females showed lower exploration. During a food challenge test at adulthood, BPS males consumed more high-fat diet at 30 min. BPS10 females initially (at 30 min) consumed more high-fat diet but, after 12 h, less of this diet was consumed. BPS50 males had hypertriglyceridemia and lower plasma T3, while BPS females showed lower plasma T4. BPS10 females had lower progesterone, whereas BPS50 females had higher plasma 25(OH)D. Maternal BPS exposure has adverse effects on the triacylglycerol, hormones levels and behavior of the progeny. Furthermore, the increased preference for the fat-enriched diet suggests an increased risk for obesity and its health consequences in the long term.