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Halofantrine (Hf) is an anti-malarial drug with a pre-ovulatory LH surge-inhibiting effect. However, the effect of Hf on in vitro maturation of oocytes (IVM) and subsequent embryo development is unknown. The aim of this study was to evaluate the effect of Hf on IVM and embryo development, and its possible mechanism. Oocytes at different maturation stages and cumulus-oocyte complexes (COCs) were harvested from ovaries of Holstein heifers and then exposed to Hf for 24 h. The influence of Hf on the mRNA expression of LH receptor (LHR) and FSH receptor (FSHR), and progesterone (P4) and 17β-estradiol (E2) secretion during IVM, and the rate of apoptosis in the oocytes and blastocysts were examined. The results showed that treatment of COCs with Hf at 0.5, 1.0, 1.5, and 2.0 μg/mL for 24 h significantly reduced the proportion of immature, metaphase II and apoptotic oocytes. Hf also reduced the maturation ratio. Moreover, Hf treatment significantly decreased the mRNA expression of LHR and FSHR, and inhibited the secretion of P4 and E2. Therefore, Hf may affect the preovulatory surge of LH and P4, and the maturation process of oocytes, resulting in inadequate development of the resulting embryos. Further studies are needed to clarify the effects of Hf on oocyte maturation and embryo development in an in vivo system. be held criminally liable under section 707(b)(1), the jury must be instructed that they can only convict the defendant of the’specified crime.'”). Accord, e.g., United States v. Kennard, 134 F.3d
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