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Embryo implantation involves a complex regulatory network of steroid hormones, inflammatory cytokines, and immune cells. Lipoxin A₄ (LXA₄), a biologically active eicosanoid with specific anti-inflammatory and pro-resolving properties, was recently found to be a novel modulator of estrogen receptor α (ERα). In this study, we investigated the potential role of LXA₄ in implantation. We found that LXA₄ blocked embryo implantation in mice and significantly reduced the expression of inflammatory mediators associated with uterine receptivity and embryo implantation, including corticotropin-releasing factor (CRF), cyclooxygenase 2-derived prostaglandin I₂ and prostaglandin E₂, leukemia inhibitory factor, and interleukin 6, but this effect was independent of LXA₄ receptor. Subsequent investigation revealed enhanced ERα activity in the uteri of LXA₄-treated mice during the peri-implantation period. ERα and phosphorylated ERα were significantly increased following LXA₄ treatment. Finally, it was demonstrated that the inhibitory effect of LXA₄ on embryo implantation was mediated through ERα. In the presence of the ERα antagonist ICI 182 780, LXA₄ failed to block embryo implantation. LXA₄ also failed to inhibit CRF expression. These results suggested that LXA₄ blocks embryo implantation by controlling ERα activity, and this effect appeared to be related to the suppression of the inflammatory microenvironment necessary for implantation.

Maternal diabetes adversely affects preimplantation embryo development and oocyte maturation. Thus, it is important to identify ways to eliminate the effects of maternal diabetes on preimplantation embryos and oocytes. The objectives of this study were to investigate whether islet transplantation could reverse the effects of diabetes on oocytes. Our results revealed that maternal diabetes induced decreased ovulation; increased the frequency of meiotic spindle defects, chromosome misalignment, and aneuploidy; increased the relative expression levels of Mad2 and Bub1; and enhanced the sensitivity of oocytes to parthenogenetic activation. Islet transplantation prevented these detrimental effects. Therefore, we concluded that islet transplantation could reverse the effects of diabetes on oocytes, and that this technique may be useful to treat the fundamental reproductive problems of women with diabetes mellitus.

The Apolipoprotein (Apo) family is implicated in lipid metabolism. There are five types of Apo: Apoa, Apob, Apoc, Apod, and Apoe. Apoe has been demonstrated to play a central role in lipoprotein metabolism and to be essential for efficient receptor-mediated plasma clearance of chylomicron remnants and VLDL remnant particles by the liver. Apo e-deficient (Apoe ^−/− ) mice develop atherosclerotic plaques spontaneously, followed by obesity. In this study, we investigated whether lipid deposition caused by Apo e knockout affects reproduction in female mice. The results demonstrated that Apoe ^−/− mice were severely hypercholesterolemic, with their cholesterol metabolism disordered, and lipid accumulating in the ovaries causing the ovaries to be heavier compared with the WT counterparts. In addition, estrogen and progesterone decreased significantly at D 100. Quantitative PCR analysis demonstrated that at D 100 the expression of cytochromeP450 aromatase (Cyp19a1), 3β-hydroxysteroid dehydrogenase (Hsd3b), mechanistic target of rapamycin (Mtor), and nuclear factor-κB (Nfkb) decreased significantly, while that of BCL2-associated agonist of cell death (Bad) and tuberous sclerosis complex 2 (Tsc2) increased significantly in the Apoe ^−/− mice. However, there was no difference in the fertility rates of the Apoe ^−/− and WT mice; that is, obesity induced by Apoe knockout has no significant effect on reproduction. However, the deletion of Apoe increased the number of ovarian follicles and the ratio of ovarian follicle atresia and apoptosis. We believe that this work will augment our understanding of the role of Apoe in reproduction.