Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes.

Maternal transfer of IgA and IgG SARS-CoV-2 specific antibodies transplacentally and via breastfeeding

Although there have been many studies on antibody responses to SARS-CoV-2 in breastmilk, very few have looked at the fate of these in the baby. We carried out a study in 22 mother/baby pairs (mothers who breastfed and who were SARS-CoV-2 vaccinated before or after delivery) looking at mother blood, mother milk, baby blood, baby nose, and baby stool. Breastfed infants only acquired systemic anti-SARS-CoV-2 IgG antibodies if their mothers were vaccinated antepartum. None of the infants had SARS-CoV-2-specific IgA in the blood, but surprisingly, half of the infants in the Antepartum group had high titer SARS-CoV-2-specific IgA in the nose that exceeded titers found in breastmilk. Vaccination antepartum followed by breastfeeding appears to be the best way to provide systemic and local anti-SARS-CoV-2 antibodies for infants.

Ontogeny of the Hapuka (Polyprion oxygeneios) Immune System

<p>In this study the ontogeny of the hapuka (Polyprion oxygeneios) immune system was studied during larval development. In teleost fish, the head kidney, thymus, and spleen are generally regarded as important immune organs. The head kidney was observed at 4 days post hatch (dph), the spleen at 16 dph and lastly the thymus at 20 dph and all 3 lymphoid organs were relatively well developed by 45 dph. The immune genes CSF1R, C3, MHCIIα, TCRα, TCRβ, RAG1, IgM and IgZ were examined by RT-PCR to investigate the leucocyte development. Macrophages appear to be present from hatch with both CSF1R and MHCIIα expression from 1 dph, while IgM is expressed at 9 dph. T-cells appear later in hapuka with TCRβ expression first detected at 32 dph whereas TCRα was not expressed until after 63 dph. Immunostaining using a monoclonal antibody against fish IgM detected IgM in the head kidney at 12 dph, the spleen at 32 dph, the intestinal tract at 45 dph and lastly the thymus at 50 dph. Comparison of the leucocyte populations in juveniles and adults indicated that innate cell populations are late to develop, while the adaptive cells mature earlier in hapuka than expected. Finally, the maternal transfer of immunity was examined and while lysozyme and IgM appear to be transferred, complement does not. Overall this study provides insight into the developmental sequence of immune organs and cells and will be useful in understanding the timing of immune competence in juveniles and adult hapuka.</p>

Ontogeny of the Hapuka (Polyprion oxygeneios) Immune System

<p>In this study the ontogeny of the hapuka (Polyprion oxygeneios) immune system was studied during larval development. In teleost fish, the head kidney, thymus, and spleen are generally regarded as important immune organs. The head kidney was observed at 4 days post hatch (dph), the spleen at 16 dph and lastly the thymus at 20 dph and all 3 lymphoid organs were relatively well developed by 45 dph. The immune genes CSF1R, C3, MHCIIα, TCRα, TCRβ, RAG1, IgM and IgZ were examined by RT-PCR to investigate the leucocyte development. Macrophages appear to be present from hatch with both CSF1R and MHCIIα expression from 1 dph, while IgM is expressed at 9 dph. T-cells appear later in hapuka with TCRβ expression first detected at 32 dph whereas TCRα was not expressed until after 63 dph. Immunostaining using a monoclonal antibody against fish IgM detected IgM in the head kidney at 12 dph, the spleen at 32 dph, the intestinal tract at 45 dph and lastly the thymus at 50 dph. Comparison of the leucocyte populations in juveniles and adults indicated that innate cell populations are late to develop, while the adaptive cells mature earlier in hapuka than expected. Finally, the maternal transfer of immunity was examined and while lysozyme and IgM appear to be transferred, complement does not. Overall this study provides insight into the developmental sequence of immune organs and cells and will be useful in understanding the timing of immune competence in juveniles and adult hapuka.</p>

Maternal 3,3’-Diiodothyronine Sulfate Formation from Guinea Pig Placenta Perfused with 3,3’,5-Triodothyronine

Objective: Serum 3, 3’,5-triiodothyronine (T3) remains low in near-term fetus to prevent the growing fetus from undue exposure to its active catabolic effect in mammals. The present study was undertaken to gain insight in the role of placenta in T3 metabolism, fetal to maternal transfer of T3, and its metabolites by in situ placenta perfusion with outer-ring labeled [125I]-T3 in pregnant guinea pig, a species showing increased sulfated 3, 3’-diiodothyronine (T2S) levels in maternal serum in late pregnancy (term = 65 days), similarly to humans in pregnancy. Materials and Methods: One-pass placenta perfusions performed on pregnant guinea pigs were studied between 58 - 65 days of gestation. In two separate experiments, the umbilical artery of the guinea pig placenta was perfused in situ at 37°C with outer-ring labeled [125I]-T3. Maternal sera and umbilical effluents were obtained for analysis at the end of a 60-minute perfusion, when the steady-state levels of radioactivity were reached in the placenta effluent after 30-minute. Results: Sulfated [125I]-T2S was readily detected in the maternal serum as the major metabolite of T3 following the perfusion of placenta with [125I]-T3, suggesting that placental inner-ring deiodinase and sulfotransferase may play an important role in fetal T3 homeostasis and in the fetal to maternal transfer of sulfated iodothyronine metabolites. Conclusions: The expression of type 3 deiodinase (D3) and thyroid hormone sulfotransferase activity in placenta may play an important role to protect developing organs against undue exposure to active thyroid hormone in late gestation in the fetus. The combined activities of D3 and sulfotransferase promoted a placental transfer of T2S into maternal circulation. The maternal circulation of T2S is fetal T3 in origin and its role as a fetal thyroid function biomarker deserves further evaluations and studies.

Placental response to maternal SARS-CoV-2 infection

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.