Adverse reproductive effects of S100A9 on bovine sperm and early embryonic development in vitro

Abstract

The phenomenon of aging arises from multiple, complex interactions causing dysfunction in cells and organs. In particular, fertility drastically decreases with age. Previously, we have demonstrated that the functional characteristics of the bovine oviduct and uterus change with the age-dependent upregulation of inflammation and noted that S100A9 triggers inflammatory responses in oviduct epithelial cells. In the present study, we investigated the hypothesis that S100A9 affects reproductive events to aspect such as sperm function, fertilization, and the development of the embryo in cows. To investigate the effect of S100A9 on bovine sperm, we incubated sperms in vitro with S100A9 for 5 h and observed significantly decreased sperm motility and viability. During in vitro fertilization, S100A9 treatment for 5 h did not affect the rate of fertilization, time of first division of embryos, or embryo development to blastocyst stage. Treatment of 2-cell stage embryos with S100A9 for 5 h significantly reduced the proportion of cells undergoing normal division (4-8 cell embryos) and embryo development to the blastocyst stage. In experiment involving 24 h treatment of 2-cell embryos, the development of all embryos stopped at the 2-cell stage in the S100A9-treated group. In blastocyst-stage embryos, S100A9 treatment significantly stimulated the expression of endoplasmic reticulum (ER) and the mRNA expression of ER stress markers, and activated caspase-3 with subsequent nuclear fragmentation. Pre-treatment with an ER stress inhibitor significantly suppressed caspase-3 activation by the S100A9 treatment, suggesting that S100A9 induces blastocyst dysfunction by apoptosis (via caspase-3 activation) depending on ER stress. These results indicate that direct exposure to S100A9 exerted adverse effects on sperm function and embryo development. These findings suggest that excessive dose of S100A9 may have an adverse effect to the reproductive machinery by inducing inflammation and tissue dysfunction. Adverse reproductive effects of S100A9 on bovine sperm and early embryonic development in vitro. PLoS ONE 15(1): e0227885. https://doi.org/ 10.

IL1B triggers inflammatory cytokine production in bovine oviduct epithelial cells and induces neutrophil accumulation via CCL2

“…Actually, although co‐culture with bovine embryos and OECs increased blastocyst formation, co‐culture with embryos and inflamed OECs induced by LPS treatment resulted in a reduction of blastocyst formation. Indeed, we reported that S100A9, one of the candidates of inflammatory trigger produced in bovine OECs, exerted adverse effects on sperm function and embryo development 44 . On the other hand, bovine OECs have an essential role to regulate embryo development and its quality in vitro via oviductal extracellular vesicles 45,46 .…”

Site specificity of blastocyst hatching significantly influences pregnancy outcomes in mice

“…The S100a9 −/− mouse is viable with normal reproductive ability, 42 and Baker et al observed no S100a9 expressed at 6.5 or 7.5 dpc wild‐type mouse embryos 43 . Nevertheless, Funeshima et al reported that S100a9 induces blastocyst dysfunction by apoptosis 44 . Further studies are needed to investigate the function of S100a9 during embryo hatching and implantation and its influence on term development.…”

“…43 Nevertheless, Funeshima et al reported that S100a9 induces blastocyst dysfunction by apoptosis. 44 Further studies are needed to investigate the function of S100a9 during embryo hatching and implantation and its influence on term development. Notably, we observed decreased S100a9 mRNA and protein expression in B-site embryos and the highest expression in C-site embryos, indicating that higher S100a9 expression at hatching stage could be related to an adverse effect on embryonic post-implantation development, poor implantation, and low birth rate.…”

Elevated S100A9 in preeclampsia induces soluble endoglin and IL-1β secretion and hypertension via the NLRP3 inflammasome

“…Importantly, S100A9 levels are elevated in the endometrial tissue of women with a recurrent history of early pregnancy loss [30,31]. Recently, we reported that exposure to S100A9 adversely affected sperm function and embryo development, and stimulated the production of inflammatory cytokines in the oviduct [32]. From all these data, we hypothesized that S100A9 may be one of the key factor linking NLRP3 inflammasome activation and HDP disorder.…”