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Embryo implantation and decidualization are crucial for a successful pregnancy. How the inflammatory response is regulated during these processes is undefined. Pyroptosis is an inflammatory form of cell death mediated by gasdermin D (GSDMD). Through in vivo, cultured epithelial cells and organoids, it is shown that pyroptosis occurs in epithelial cells at the implantation site. Compared with those on day 4 of pseudopregnancy and delayed implantation, pyroptosis-related protein levels are significantly increased on day 4 of pregnancy and activated implantation, suggesting that blastocysts are involved in regulating pyroptosis. Blastocyst-derived cathepsin B (CTSB) is stimulated by preimplantation estradiol-17β and induces pyroptosis in epithelial cells. Pyroptosis-induced IL-18 secretion from epithelial cells activates a disintegrin and metalloprotease 12 (ADAM12) to process the epiregulin precursor into mature epiregulin. Epiregulin (EREG) enhances in vitro decidualization in mice. Pyroptosis-related proteins are detected in the mid-secretory human endometrium and are elevated in the recurrent implantation failure endometrium. Lipopolysaccharide treatment in pregnant mice causes implantation failure and increases pyroptosis-related protein levels. Therefore, the data suggest that modest pyroptosis is beneficial for embryo implantation and decidualization. Excessive pyroptosis can be harmful and lead to pregnancy failure., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Preeclampsia is associated with over-activation of the innate immune system in the placenta, in which toll-like receptor 4 (TLR4) plays an essential part. With their potent anti-inflammatory effects, statins have been suggested as potential prevention or treatment of preeclampsia, although evidence remains inadequate. Herewith, we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide (LPS)-induced rat preeclampsia model, through targeting the TLR4/NF-κB pathway. The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day (GD) 12, (101.33±2.49) mmHg vs. (118.3±1.37) mmHg, P<0.05] and urine protein level [maximum decline on GD9, (3,726.23±1,572.86) μg vs. (1,991.03±609.37) μg, P<0.05], which were elevated following LPS administration. Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats (34.10% vs. 8.99%, P<0.05). Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment. These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum. Additionally, no obvious abnormalities in fetal liver, brain, and kidney were found after administration of pravastatin. These results provide supportive evidence for use of pravastatin in preventing preeclampsia.

We have developed a "combination culture system", composed of primary differentiated granulosa cells, proestrus anterior pituitary lobe and delta-4-androstenedione. This cultured system effectively induce the maturation of oocytes from early tertiary follicles of diethylstilbestrol (DES)-treated rats. After DES stimulation, an average of 189 oocytes were obtained from early tertiary follicles of unilateral ovaries; 78% of these oocytes, when cultured in this culture system, extruded the first polar body, a criterion of oocyte maturation. Of the mature oocytes, the rate of normal fertilization and egg cleavage were 88% and 93%, respectively. After 96 h of culturing in vitro, 59% of the zygotes developed into morulae or blastocysts. Embryos implanted at the two-cell stage were able to develop into healthy individuals. Thus the combination culture system provides an experimental model in which the molecular mechanisms of egg maturation, fertilization, and embryonic development can be studied.

The eukaryotic expression plasmid pEGFP-N1/DPF-1 was constructed through fusing rabbit oviduct-specific glycoprotein (DPF-1) gene to the 5' terminus of eGFP gene. After transfecting the recombinant plasmid into HeLa cells, we got some cell strains expressing and secreting eGFP-DPF-1 stably. The apparent molecular weight of the fusion protein was up to 120 KD indicating the fusion protein was modified. Rabbit oocyte-cumulus cells complexes (COC), the cumulus cells-deprived oocytes or oviductal oocytes were co-cultured with the cell strain or cultured in the conditioned medium derived from the cell strain to observe the distribution of DPF-1 in oocytes after incubation. The results revealed that DPF-1 but not GFP alone associated with zona pellucidae (ZP) of oocytes, especially in the inner layer of ZP, and was evenly distributed in dot-like shape on the outer surface of the cytoplasmic membrane. In contrast, the cumulus cells around the oocyte did not interfere the association of DPF-1 with oocyte, and no trace of DPF-1 was found in the cumulus cells. The experiment proved that the oviductin expressed and secreted by eukaryotic cells in vitro could bind to oocytes, and was directly observed by using green fluorescent protein as a tracer. These results provided some interesting informations for the further studying on the functions of the oviductin.