To understand the effect of fetal thyroid gland disruption on development in swine, we evaluated thyroid hormone levels, growth and developmental characteristics, and gene expression associated with thyroid hormone metabolism in late gestation fetuses exposed to methimazole (MMI). Pregnant gilts were given either oral MMI or equivalent sham from gestation day 85–106 (n = 4/group), followed by intensive phenotyping of all fetuses (n = 120). Samples of liver (LVR), kidney (KID), fetal placenta (PLC) and the corresponding maternal endometrium (END) were collected from a subset of fetuses (n = 32). Fetuses exposed to MMI in utero were confirmed hypothyroid, with a significant increase in thyroid gland size, goitrous thyroid histology, and dramatically suppressed thyroid hormone in serum. In the dams, no differences in temporal measurements of average daily gain, thyroid hormone, or rectal temperatures relative to controls suggest that MMI had little effect on maternal physiology. However, fetuses from MMI treated gilts exhibited significant increases in body mass, girth, and vital organ weights, but no differences in crown-rump length or bone measurements suggest non-allometric growth. The PLC and END showed a compensatory decrease in expression of inactivating deiodinase (DIO3). Similar compensatory gene expression was observed in fetal KID and LVR with a downregulation of all deiodinases (DIO1, DIO2, DIO3). Minor alterations in the expression of thyroid hormone transporters (SLC16A2 and SLC16A10) were observed in PLC, KID and LVR. Collectively, MMI crosses the fetal placenta of the late gestation pig, resulting in congenital hypothyroidism, alterations in fetal growth, and compensatory responses within the maternal fetal interface.
Porcine reproductive and respiratory syndrome virus (PRRSV) in late gestation causes a profound suppression of circulating maternal and fetal thyroid hormone during a critical window of development. To understand this relationship, we evaluated thyroid hormone metabolism at the maternal–fetal interface and within fetal tissues, along with hormone metabolite levels in serum. Fetuses were classified using an established model based on viral load in serum and thymus, and preservation status, including uninfected (UNIF), high-viral load viable (HV-VIA), and high-viral load meconium-stained (HV-MEC), with additional controls from sham-inoculated gilts (CON). Expression of three iodothyronine deiodinases, five sulfotransferases, sulfatase, and two solute carriers known to transport thyroid hormone were evaluated in maternal endometrium and fetal placenta, liver, and kidney. Serum thyroxin (T4), reverse triiodothyronine (rT3), and diiodothyronine (T2) were evaluated via liquid chromatography tandem mass spectrometry. Significant changes in gene expression were observed in all four tissues, with the liver being the most severely impacted. We observed local and fetal specific regulation of maternal tissues through significant upregulation of DIO2 and DIO3 expression in the endometrium corresponding to infected but viable fetuses relative to uninfected and control fetuses. Expression levels of DIO2 and DIO3 were significantly higher in the resilient (HV-VIA) fetuses relative to the susceptible (HV-MEC) fetuses. A substantial decrease in serum T4 was confirmed, with no corresponding increase in rT3 or T2. Collectively, these results show that thyroid hormone metabolism is altered at the maternal–fetal interface and within the PRRSV infected fetus and is associated with fetal viability.
Perinatal nutrition affects future milk production. The number of mammary epithelial cells affect milk production capacity. Therefore, it was hypothesized that the level of colostrum intake affects the proliferation rate and the total number of mammary epithelial cells in the gland. The ratio of newly synthesized protein to newly synthesized DNA reflects the relative amount of cellular differentiation to cell division. The study objective was to determine the relationship between the level of colostrum intake and 24 h-level of circulating amino acid, glucose and insulin with mammary parenchyma histological features, cell division and protein synthesis over the first week postnatal. One of two standardized doses of a homogenate colostrum sample, 10% (n = 8) and 20% (n = 8) of birth bodyweight, was fed to gilts over the first 24 h postnatal. Gilts were administered deuterium oxide immediately after birth and daily to label newly synthesized DNA and proteins. Gilts were euthanized on postnatal day seven, and DNA and protein were isolated from mammary parenchyma. DNA and protein fractional synthesis (f) and fractional synthetic rate (FSR) were calculated using mass isotopomer distribution analysis. The ratio of protein f and FSR to DNA f and FSR were calculated and used to indicate the relative amounts of differentiation to cell division. Mammary morphological development was also analyzed by measuring the parenchymal epithelial area and the stromal and epithelial proliferation index on postnatal day seven. Colostrum dose was not related to any of the variables used to evaluate mammary development. However, plasma lysine levels at 24 h postnatal were positively related to average daily gain (ADG; r = 0.54, p = 0.05), DNA f (r = 0.57; p = 0.03) and DNA FSR (r = 0.57; p = 0.03) in mammary parenchyma. Plasma lysine was inversely related to the ratio of protein to DNA f and FSR (r = −0.56; p = 0.04). ADG was related to the parenchymal epithelial area and DNA and protein f and FSR (p < 0.05). These relationships support the idea that the nutritional environment affects early mammary development and that higher lysine levels in the perinatal period favored a greater degree of cell division versus differentiation in mammary of neonatal pigs and thus, warrant further investigations.
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