Pregnancy, Viral Infection, and COVID-19.

Pregnancy comprises a unique immunological condition, to allow fetal development and to protect the host from pathogenic infections. Viral infections during pregnancy can disrupt immunological tolerance and may generate deleterious effects on the fetus. Despite these possible links between pregnancy and infection-induced morbidity, it is unclear how pregnancy interferes with maternal response to some viral pathogens. In this context, the novel coronavirus (SARS-CoV-2) can induce the coronavirus diseases-2019 (COVID-19) in pregnant women. The potential risk of vertical transmission is unclear, babies born from COVID-19-positive mothers seems to have no serious clinical symptoms, the possible mechanisms are discussed, which highlights that checking the children's outcome and more research is warranted. In this review, we investigate the reports concerning viral infections and COVID-19 during pregnancy, to establish a correlation and possible implications of COVID-19 during pregnancy and neonatal's health.

Natural Killer Cell Reduction and Uteroplacental Vasculopathy.

Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth.

Maternal immune responses to conceptus signals during early pregnancy in ruminants

Pregnancy is an immunological paradox created by the hospitable interaction between the maternal immune system and the allogeneic concept us in the gravid uterus. The mother is not immune - suppressed during early pregnancy, nor is the conceptus immune-privileged, shielding itself from maternal immune detection by an immunologically inert placenta. Rather, what is becoming clear is that the conceptus and other endocrine mediators, including progesterone, actively shape the maternal immune response during early pregnancy to facilitate growth and development of a functioning placenta. In this regard, conceptual thinking derived from immune cell–pathogen interactions inadequately describe the unique homeorhetic mechanisms mediating early conceptus-maternal interactions. Nonetheless, evidence is mounting that conceptus signals induce a tolerogenic (Th2) bias in immune cell function at the fetal-maternal interface. This is accompanied by tissue remodeling and angiogenesis facilitated by tissue-resident immune cells that sets the trajectory for placental growth and, ultimately, fetal growth. Perturbations in these interactions, including systemic inflammation and various stressors at the earliest stages of pregnancy can interfere with communication between the conceptus and uterus , reducing conception rates and resulting in poor pregnancy outcomes.

Maternal immune responses to conceptus signals during early pregnancy in ruminants

Pregnancy is an immunological paradox created by the hospitable interaction between the maternal immune system and the allogeneic concept us in the gravid uterus. The mother is not immune - suppressed during early pregnancy, nor is the conceptus immune-privileged, shielding itself from maternal immune detection by an immunologically inert placenta. Rather, what is becoming clear is that the conceptus and other endocrine mediators, including progesterone, actively shape the maternal immune response during early pregnancy to facilitate growth and development of a functioning placenta. In this regard, conceptual thinking derived from immune cell–pathogen interactions inadequately describe the unique homeorhetic mechanisms mediating early conceptus-maternal interactions. Nonetheless, evidence is mounting that conceptus signals induce a tolerogenic (Th2) bias in immune cell function at the fetal-maternal interface. This is accompanied by tissue remodeling and angiogenesis facilitated by tissue-resident immune cells that sets the trajectory for placental growth and, ultimately, fetal growth. Perturbations in these interactions, including systemic inflammation and various stressors at the earliest stages of pregnancy can interfere with communication between the conceptus and uterus , reducing conception rates and resulting in poor pregnancy outcomes. (AU)

Maternal immunization with ovalbumin prevents neonatal allergy development and up-regulates inhibitory receptor Fc gamma RIIB expression on B cells.

BACKGROUND: Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. RESULTS: Maternal immunization with OVA showed increased levels of Fc gamma RIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-gamma-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specific IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced Fc gamma RIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. CONCLUSION: Maternal immunization upregulates the inhibitory Fc gamma RIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.

Efectos mnemónicos maternos prenatales sobre el sexo psíquico humano: insuficiencia del mecanismo inmunitario: nueva propuesta desde la tolerancia-rechazo materno-fetal / Prenatal maternal mnemonic effects on the human neuro-psychic sex: a new proposition from fetus-maternal tolerance-rejection

In approximately 15 percent of homosexual men, their phenotype is associated to the fraternal birth order. Older biological brothers induce in their mothers anti-male factors (antibodies) that interfere the brain maleness development ofyounger fetuses. This effect is seldom seen in non-right-handed men and is not seen in women. The influence of older siblings is seen in their sex ratio (SR). In contradiction with previous hypothesis, significant heterogeneities of SR have been found among older siblings of males or females, right or non-right-handed and homo or heterosexual individuáis. This can only be understood as if the ñndings found among homosexuals were part of a general mechanism of fetus-maternal tolerance-rejection processes of placental mammals. We found, in relation to ABO and Rh systems and sex, that embryos with genes different from those of their mothers, induced better pregnancies and maternal tolerance than embryos similar to their mothers. Assuming that homo or heterosexuality and right or non-right-handedness behave similar to ABO or Rh alíeles, the author provides a speculative interpretation ofthese results. Homosexual women (¡esbians) and especially if they are non-right-handed, are preceded by siblings with a high SR (maternal environment with anti-female or pro-male factors); then lesbianism or non-right-handedness may induce tolerance to be a woman in such anti-female environment. Non-right-handedness could induce tolerance for anti-male factors of mothers, thus preventing the production ofgays in a pro-male maternal environment, but leading to the production of non-right-handed gays in anti-male maternal environments. Several new hypotheses and interpretations merge from this newproposition. Also, complete sexual orientation could be acquired after birth.

Proteção fetal contra o vírus da diarréia viral bovina (BVDV) em vacas prenhes previamente imunizadas com uma vacina experimental atenuada / Fetal protection against bovine viral diarrhea virus (BVDV) in pregnant cows previously immunized with an experimental attenuated vaccine

Esse artigo relata a avaliação da resposta sorológica e proteção fetal conferida por uma vacina experimental contendo duas amostras atenuadas do vírus da diarréia viral bovina tipos 1 (BVDV-1) e 2 (BVDV-2). Vacas foram imunizadas com a vacina experimental (n=19) e juntamente com controles não-vacinadas (n=18) foram colocadas em cobertura e desafiadas, entre os dias 60 e 90 de gestação, pela inoculação intranasal de quatro amostras heterólogas de BVDV-1 e BVDV-2. A resposta sorológica foi avaliada por testes de soro-neutralização realizados a diferentes intervalos após a vacinação (dias 34, 78 e 138 pós-vacinação [pv]). A proteção fetal foi monitorada por exames ultra-sonográficos e clínicos realizados durante o restante da gestação; e pela pesquisa de vírus e anticorpos no sangue pré-colostral coletado dos fetos abortados e/ou dos bezerros recém nascidos. No dia do desafio (dia 138 pv), todas as vacas vacinadas apresentavam anticorpos neutralizantes em títulos altos contra o BVDV-1 (1.280- >10.240) e, com exceção de uma vaca (título 20), todas apresentavam títulos médios a altos contra o BVDV-2 (80-1.280). O monitoramento da gestação revelou que, dentre as 18 vacas não-vacinadas, apenas três (16,6 por cento) pariram bezerros saudáveis e livres de vírus. As 15 restantes (83,3 por cento) apresentaram indicativos de infecção fetal e/ou falhas reprodutivas. Sete dessas vacas (38,8 por cento) pariram bezerros positivos para o vírus, sendo que cinco eram saudáveis e sobreviveram (27,7 por cento); e dois apresentavam sinais de prematuridade ou fraqueza e morreram três e 15 dias após o nascimento, respectivamente. As oito vacas controle restantes (44,4 por cento) abortaram entre o dia 30 pós-desafio e às proximidades do parto, ou deram à luz bezerros prematuros, inviáveis ou natimortos. Por outro lado, 17 de 19 (89,4 por cento) vacas vacinadas deram à luz bezerros saudáveis e livres de vírus. Uma vaca vacinada abortou 130 dias pós-desafio, mas...(AU)

This paper reports the antibody response and fetal protection in pregnant cows conferred by an experimental vaccine containing two attenuated strains of bovine viral diarrhea virus (BVDV-1 and BVDV-2). Cows (n=19) were vaccinated twice, with a 34 days-interval, with the experimental vaccine and together with non-vaccinated controls (n=18), were mated and challenged between days 60 and 90 of gestation by intranasal inoculation of four heterologous BVDV-1 and BVDV-2 isolates. The antibody response was evaluated by serum-neutralization tests performed at different intervals after vaccination (days 34, 78 and 138 post-vaccination [pv]). Fetal protection was monitored by ultrassonographic and clinical examination of the dams and fetuses during the rest of gestation; and through virological and serological examination of pre-colostral blood obtained from aborted and/or recently born fetuses/calves. At the day of challenge (day 138 pv), all vaccinated cows had neutralizing antibodies in high titers against BVDV-1 (1,280->10,240), and with one exception (titer 20), presented moderate to high titers to BVDV-2 (80-1,280). At the end of the monitoring, only three out of 18 control cows (16.6 percent) delivered healthy, virus-free calves. Fifteen non-vaccinated cows (83.3 percent) presented signs of fetal infection and/or had reproductive losses. Seven of these cows (38.8 percent) delivered virus-positive calves; five were healthy and survived (27.7 percent); two were premature or weak and lasted three and 15 days, respectively. The other eight cows (44.4 percent) aborted between day 30 post-challenge and the parturition; or delivered premature or stillbirth calves. In contrast, 17 out of 19 (89.4 percent) vaccinated cows delivery virus-free, healthy calves. One vaccinated cow aborted around day 130 post-challenge, yet this fetus could not be examined for the presence of virus. Another cow delivered a virus-positive calf (5.2 percent). In summary...(AU)

[Prenatal maternal mnemonic effects on the human neuro-psychic sex: a new proposition from fetus-maternal tolerance-rejection]. / Efectos mnemónicos maternos prenatales sobre el sexo psíquico humano. Insuficiencia del mecanismo inmunitario: Nueva propuesta desde la tolerancia-rechazo materno-fetal.

In approximately 15% of homosexual men, their phenotype is associated to the fraternal birth order. Older biological brothers induce in their mothers anti-male factors (antibodies) that interfere the brain maleness development of younger fetuses. This effect is seldom seen in non-right-handed men and is not seen in women. The influence of older siblings is seen in their sex ratio (SR). In contradiction with previous hypothesis, significant heterogeneities of SR have been found among older siblings of males or females, right or non-right-handed and homo or heterosexual individuals. This can only be understood as if the findings among homosexuals were part of a general mechanism of fetus-maternal tolerance-rejection processes of placental mammals. We found, in relation to ABO and Rh systems and sex, that embryos with genes different from those of their mothers, induced better pregnancies and maternal tolerance than embryos similar to their mothers. Assuming that homo or heterosexuality and right or non-right-handedness behave similar to ABO or Rh alleles, the author provides a speculative interpretation of these results. Homosexual women and especially if they are non-right-handed, are preceded by siblings with a high SR (maternal environment with anti-female or pro-male factors); then lesbianism or non-right-handedness may induce tolerance to be a woman in such anti-female environment. Non-right-handedness could induce tolerance for anti-male factors of mothers, thus preventing the production of gays in a pro-male maternal environment, but leading to the production of non-right-handed gays in anti-male maternal environments. Several new hypotheses and interpretations merge from this new proposition. Also, complete sexual orientation could be acquired after birth.