Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex(COC);however,their role in mammalian fertilization remains unclear.P...Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex(COC);however,their role in mammalian fertilization remains unclear.Previously,we have shown that hyaluronidase 5(Hyal5)/Hyal7 double-knockout(dKO)mice produce significantly fewer offspring than their wild-type(WT)counterparts because of defective COC dispersal.Male infertility is mainly caused by a low sperm count.It can be further exacerbated by the deficiency of sperm hyaluronidase,which disperses the cumulus cells of the outer layer of the COC.In the current study,we evaluated the effects of a low count of Hyal-deficient sperm and conditions of ovulated oocytes on the fertilization rate using a mouse model.Our results demonstrated that a low sperm count further decreases the in vitro fertilization(IVF)rate of Hyal-deficient dKO spermatozoa.In addition,the dKO spermatozoa resulted in a fertilization rate of 12.5%upon fertilizing COCs with a thick cumulus layer,whereas the IVF rate was comparable to that of WT spermatozoa when oocytes with a thin or no cumulus layer were fertilized.Finally,we proved that the IVF rate of dKO spermatozoa could be recovered by adding rat spermatozoa as a source of sperm hyal.Our results suggest that a deficiency of proteins involved in fertilization,such as sperm hyal,has a vital role in fertilization.展开更多
Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction ...Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction （八物汤, BWD, Palmul-tang in Korean）. Methods： Methylceliulose （MC, control）, GPD （1,200 mg/kg）, or BWD （6,000 mg/kg） was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib （10 mg/kg） was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib （10 mg/kg） was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results： Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration （Crux, P〈0.05） and area under the curve （P〈0.05）, and a delayed time to reach Cmax （Tmax, P〈0.01） were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions： BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.展开更多
基金supported by the KRIBB Research Initiative Program(KGM4252122)the National Research Foundation(2018M2A9Hl078340)the National Research Foundation of Korea Grant funded by the Korean Government(NRF-2020R111A3072358).
文摘Glycosylphosphatidylinositol-anchored sperm hyaluronidases have long been believed to assist in sperm penetration through the cumulus-oocyte complex(COC);however,their role in mammalian fertilization remains unclear.Previously,we have shown that hyaluronidase 5(Hyal5)/Hyal7 double-knockout(dKO)mice produce significantly fewer offspring than their wild-type(WT)counterparts because of defective COC dispersal.Male infertility is mainly caused by a low sperm count.It can be further exacerbated by the deficiency of sperm hyaluronidase,which disperses the cumulus cells of the outer layer of the COC.In the current study,we evaluated the effects of a low count of Hyal-deficient sperm and conditions of ovulated oocytes on the fertilization rate using a mouse model.Our results demonstrated that a low sperm count further decreases the in vitro fertilization(IVF)rate of Hyal-deficient dKO spermatozoa.In addition,the dKO spermatozoa resulted in a fertilization rate of 12.5%upon fertilizing COCs with a thick cumulus layer,whereas the IVF rate was comparable to that of WT spermatozoa when oocytes with a thin or no cumulus layer were fertilized.Finally,we proved that the IVF rate of dKO spermatozoa could be recovered by adding rat spermatozoa as a source of sperm hyal.Our results suggest that a deficiency of proteins involved in fertilization,such as sperm hyal,has a vital role in fertilization.
基金Supported by the Comprehensive and Interactive Medicine InstituteNational Research Foundation of Korea(No.2012R1A2A2A02044997)
文摘Objective： To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib （Iressae） and the oriental medications Guipi Decoction （归脾汤, GPD, Guibi-tang in Korean） and Bawu Decoction （八物汤, BWD, Palmul-tang in Korean）. Methods： Methylceliulose （MC, control）, GPD （1,200 mg/kg）, or BWD （6,000 mg/kg） was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib （10 mg/kg） was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib （10 mg/kg） was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results： Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration （Crux, P〈0.05） and area under the curve （P〈0.05）, and a delayed time to reach Cmax （Tmax, P〈0.01） were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions： BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.
