High fat diet alters male seminal plasma composition to impair female immune adaptation for pregnancy in mice

Paternal experiences and exposures prior to conception can influence fetal development and offspring phenotype. The composition of seminal plasma contributes to paternal programming effects, through modulating the female reproductive tract immune response after mating. To investigate whether paternal obesity affects seminal plasma immune-regulatory activity, C57Bl/6 male mice were fed an obesogenic high fat diet (HFD) or control diet (CD) for 14 weeks. While HFD consumption caused only minor changes to parameters of sperm quality, the volume of seminal vesicle fluid secretions was increased by 65%, and the concentrations and total content of immune-regulatory TGFB isoforms were decreased by 75-80% and 43-55% respectively. Mating with BALB/c females revealed differences in the strength and properties of the post-mating immune response elicited. Transcriptional analysis showed >300 inflammatory genes were similarly regulated in the uterine endometrium by mating independently of paternal diet, but 13 were dysregulated by HFD-fed compared to CD-fed males. Seminal vesicle fluid factors reduced in HFD-fed males, including TGFB1, IL10, and TNF, were amongst the predicted upstream regulators of differentially regulated genes. Additionally, the T cell response induced by mating with CD-fed males was blunted after mating with HFD-fed males, with 27% fewer CD4 + T cells, 26% fewer FOXP3 +CD4 + regulatory T cells (Treg) cells, and 19% fewer CTLA4 + Treg cells, particularly within the NRP1 + thymic Treg cell population. These findings demonstrate that an obesogenic high fat diet alters the composition of seminal vesicle fluid and impairs seminal plasma capacity to elicit a favorable pro-tolerogenic immune response in females at conception.

Cutaneous Manifestations in Confirmed COVID-19 Patients: A Systematic Review

There have been increasing reports of skin manifestations in COVID-19 patients. We conducted a systematic review and included manuscripts describing patients with positive RT-PCR coronavirus testing from nasopharyngeal swabs who also developed cutaneous manifestations. A total of 655 patients were selected, with different types of skin rashes: Erythematous maculopapular (n = 250), vascular (n = 146), vesicular (n = 99), urticarial (n = 98), erythema multiforme/generalized pustular figurate erythema/Stevens-Johnson syndrome (n = 22), ocular/periocular (n = 14), polymorphic pattern (n = 9), generalized pruritus (n = 8), Kawasaki disease (n = 5), atypical erythema nodosum (n = 3), and atypical Sweet syndrome (n = 1). Chilblain-like lesions were more frequent in the younger population and were linked to a milder disease course, while fixed livedo racemosa and retiform purpura appeared in older patients and seemed to predict a more severe prognosis. For vesicular rashes, PCR determined the presence of herpesviruses in the vesicle fluid, which raised the possibility of herpesvirus co-infections. The erythema-multiforme-like pattern, generalized pustular figurate erythema and Stevens-Johnson syndrome were most frequently linked to hydroxychloroquine intake. A positive PCR determination of SARS-COV-2 from conjunctival swabs suggest that eye discharge can also be contagious. These cutaneous manifestations may aid in identifying otherwise asymptomatic COVID-19 carriers in some cases or predict a more severe evolution in others.

In vitro metabolomic footprint of the Echinococcus multilocularis metacestode

Alveolar echinococcosis (AE) is a zoonotic disease that is deadly if left untreated. AE is caused by the larval metacestode stage of the cestode Echinococcus multilocularis. Better knowledge on the host-parasite interface could yield novel targets for improvement of the treatment against AE. We analyzed culture media incubated with in vitro grown E. multilocularis metacestodes by 1H nuclear magnetic resonance spectroscopy to identify the unknown metabolic footprint of the parasite. Moreover, we quantitatively analyzed all amino acids, acetate, glucose, lactate, and succinate in time-course experiments using liquid chromatography and enzymatic assays. The E. multilocularis metacestodes consumed glucose and, surprisingly, threonine and produced succinate, acetate, and alanine as major fermentation products. The metabolic composition of vesicle fluid (VF) from in vitro grown E. multilocularis metacestodes was different from parasite-incubated culture medium with respect to the abundance, but not the spectrum, of metabolites, and some metabolites, in particular amino acids, accumulated in the VF. Overall, this study presents the first characterization of the in vitro metabolic footprint of E. multilocularis metacestodes and VF composition, and it provides the basis for analyses of potentially targetable pathways for future drug development.