Coronavirus disease 2019 (COVID-19) is a pneumonia pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 1 First identified in December 2019 in an outbreak of pneumonia in Wuhan City (Hubei Province, China), COVID-19 currently affects over 210 countries and territories worldwide. 2 The World Health Organization (WHO) declared COVID-19 to be a Public Health Emergency of International Concern, 3 then a pandemic, on March 11, 2020. 4 By June 30, 2020, there had been over 10 million confirmed cases, including over 500.000 patient deaths. 2 The majority of COVID-19 patients manifest mild to moderate symptoms; approximately 15% progress to the severe form of the

Dysfunction of decidual macrophages (DMs) is considered a critical event in the pathogenesis of pre-eclampsia (PE). T cell immunoglobulin mucin 3 (Tim-3) is an important negative regulatory molecule that induces immune tolerance by interacting with its ligand Galectin-9 (Gal-9) and thus modulating function of various immune cells, including macrophages. However, the regulatory effects of Tim-3/Gal-9 signaling on DMs polarization and its role in PE remain unclear. In this study, we established a PE-like rat model by administering 1.0 μg/kg lipopolysaccharide (LPS) to normal pregnant Sprague-Dawley rats via the tail vein at embryonic day 5 (E5). Apart from the pre-eclamptic manifestations, increased M1 subtype and decreased M2 subtype were observed at the maternal-fetal interface, as well as increased pro-inflammatory cytokines (TNF-α and IL-1β) and reduced anti-inflammatory cytokines (TGF-β and IL-10). Moreover, the expression of Tim-3 in DMs and that of Gal-9 at the maternal-fetal interface were reduced. After administration of recombinant Galectin-9 (rGal-9) protein, we found that liver and renal injuries and maternofetal placental functional deficiency, including inadequate trophoblast cells invasion, impaired spiral artery remodeling and fetal capillary development, were reversed. In addition, the polarization of DMs was inclined to M2 subtype, which was similar to the polarization of DMs in the control rats but contrary to the PE-like rats. Interestingly, at E9, the expression of Tim-3 in DMs and that of Gal-9 at the maternal-fetal interface were significantly increased in the rGal-9 protein intervention group. Taken together, our findings show that administration of rGal-9 protein can alleviate the PE-like rat manifestations induced by LPS. This finding may be related to the activation of the Tim-3/Gal-9 signaling pathway, which promotes DMs polarization dominantly shifting to M2 subtype. Moreover, upregulation of Tim-3 in DMs and Gal-9 at the maternal-fetal interface at E9 suggests that Tim-3/Gal-9 pathway may play some important roles in early pregnancy and even embryo development.

Recurrent spontaneous abortion (RSA) is a growing problem worldwide. In a majority of cases, the cause remains unknown but there is increasing evidence that immunologic factors play an important role. Intravenous immunoglobulin (IVIg) therapy has been proposed to have immune modulatory effects and therefore been applicable for the treatment of patients with RSA. Although its efficacy is still controversial, several recent studies suggest that IVIg treatment may improve pregnancy outcomes. CD4 T cells and their related cytokines play an important role in maternal-fetal immune regulation, and an imbalance of Th17/Treg cell ratio has been proposed as a cause for RSA. We review the scientific evidence supporting a modulatory effect of IVIg on Th17/Treg cell balance and discuss the potential mechanisms how IVIg might enhance Treg cells function. We propose that correction of Th17/Treg cell dysregulation could be one of the mechanisms that can explain the positive therapeutic effects of IVIg therapy. Consequently, selecting patients with abnormal Th17/Treg cell ratios could increase the success of IVIg therapy.

Aerobic glycolysis is a recognized feature shared by tumors, leading to the accumulation of lactic acid in their local microenvironments. Like the tumors, the blastocysts, placenta, trophoblasts and decidual immune cells can also produce a large amount of lactic acid through aerobic glycolysis during the early pregnancy. Moreover, the placenta expresses the transporters of the lactic acid. While several studies have described the role of lactic acid in the tumor microenvironment, especially lactic acid's modulation of immune cells, the role of lactic acid produced during pregnancy is still unclear. In this paper, we reviewed the scientific evidence detailing the effects of lactic acid in the tumor microenvironment. Based on the influence of the lactic acid on immune cells and tumors, we proposed that lactic acid released in the unique uterine environment could have similar effects on the trophoblast cells and immune cells during the early pregnancy.

Lactic acid (LA) metabolism in the tumor microenvironment contributes to the establishment and maintenance of immune tolerance. This pathway is characterized in tumor associated macrophages. However, the role and pathway of LA metabolism at maternal-fetal interface during early pregnancy, especially in decidual macrophage differentiation, are still unclear. Herein, for the first time, we discovered that LA can trigger either M2 or M1 macrophage polarization via oxidative phosphorylation and glycolysis regulation under normoxia or hypoxia, respectively. Also, LA metabolism played a vital role in decidual macrophages-mediated recurrent pregnancy loss (RPL), through HIF-1α/SRC/LDHA pathway. Moreover, blockade of LA intake with AZD3965 (MCT-1 inhibitor) could rescue pregnancy in an abortion-prone mouse model, suggesting a potential therapeutic target in RPL. Collectively, the present study identifies the previously unknown functions of LA metabolism in the differentiation of decidual macrophages in early normal pregnancy and RPL, and provides a potential therapeutic strategy in RPL by manipulating decidual macrophages' functions through LA metabolic pathway.

The well-established classic role of vitamin D is implicated in the regulation of the balance between calcium and phosphorus. Furthermore, vitamin D is also involved in many non-classic physiological processes, mainly including the regulation of cell proliferation, differentiation, apoptosis and immune function, participation in the inflammatory response and maintenance of genome stability function. During pregnancy, vitamin D receptor and its metabolic enzymes are expressed at the placenta and decidua, indicating the potential role in the mechanism of immunomodulation at the maternal-fetal interface. The insufficiency or deficiency of vitamin D may affect the mother directly and is related to specific pregnancy outcomes, such as preeclampsia, gestational diabetes, and recurrent miscarriage. This article reviews the effects of vitamin D on immune regulation during pregnancy.

Successful pregnancy is a unique situation requires the maternal immune system to recognize and tolerate a semi‐identical fetus and allow normal invasion of trophoblast cells. Although efforts have been made, the deep mechanisms of the maternal‐fetal crosstalk have not yet been fully deciphered. Immune checkpoint molecules (ICMs) are a group of negative modulators of the immune response that avoid immune damage. They have been extensively studied in the fields of oncology and transplantation, while the latest evidence suggests that they are closely associated with pregnancy outcomes via multiple inhibitory mechanisms. Although studies have mostly demonstrated the regulatory role of the well‐known PD‐1, CTLA‐4 at the maternal‐fetal interface, what is unique about the newly discovered multiple ICMs remains a mystery. Here, we review the latest knowledge on ICMs, focusing on the first generation of checkpoints (PD‐1, CTLA‐4) and the next generation (Tim‐3, Tigit, Lag‐3, VISTA) highlighting their immunoregulatory roles in maternal‐fetal tolerance and decidual vascular remodeling, and their involvement in pathological pregnancies. The content covers three aspects: the characteristics they possess, the dynamic expression profile of their expression at the maternal‐fetal interface, and their involvement in pathological pregnancy. In immunotherapy strategies for pregnancy complications, upregulation of immune checkpoints may play a role. Meanwhile, the impact on pregnancy outcomes when using ICMs in clinical cancer treatment during pregnancy is a topic worth exploring. These may serve as a guide for future basic research and clinical applications of maternal‐fetal immunity.

Background: Domestic violence does not only violate women's fundamental human rights but it also undermines them from achieving their fullest potential around the world. This study was conducted to assess trends and factors associated with domestic violence among married women of reproductive age in Zimbabwe. Method: This was a cross-sectional study which used secondary data obtained from 2005/06, 2010/11 and 2015 Zimbabwe Demographic and Health Surveys (ZDHS). Respondents ranged from married or living with a partner (15-49 years). Multiple logistic regression analysis was used to examine factors associated with domestic violence. Results: Out of 4472 women who were currently married, 1907 (42.7%) had ever experienced one form of domestic violence (physical, emotional and sexual violence). Women aged 40-49 was deemed a protective factor against domestic violence. Risk of domestic violence was higher among working women than unemployed women [AOR = 1.35; p ≤ 0.047]. Women who drink alcohol significantly risk experiencing domestic violence compared to their non-drinking counterpart; also women whose husbands drink alcohol were at higher risk of experiencing domestic violence [AOR = 1.35; p ≤ 0.001]. Domestic violence was higher among women whose husbands have ever experienced their fathers beating their mothers and significant for women whose husbands have more than one wife (polygamy) [AOR = 1.35; p ≤ 0.001]. High parity (5 or more children) was also a risk factor for domestic violence among the studied population [AOR = 1.35; p ≤ 0.038]. Conclusion: Domestic violence was found to be strongly associated with women whose husbands drink alcohol, products of abusive parents/father beating their mother and/or polygamous marriage (had more than one wife). Domestic violence still remains a challenge and a more biting policy efforts are needed to eradicate this public health canker in Zimbabwe.