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Abstract：
OBJECTIVE: To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process.
METHODS: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined.
RESULTS: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs.
CONCLUSIONS: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.
METHODS: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined.
RESULTS: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs.
CONCLUSIONS: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.
摘要：
目的：探讨不育症患者血铅水平（BLL）与IVF临床结局的关系，并进一步探讨颗粒细胞（GC）内质网（ER）应激可能参与该过程。
方法：本研究纳入了123名接受IVF周期的不孕妇女。所有参与者都被分成三个(低，中等,和高)由BLL三元率确定的组。促性腺激素释放激素（GnRH）激动剂方案用于所有患者的卵巢刺激，在取卵当天收集卵泡液。检测卵泡液中乳酸脱氢酶（LDH）水平和颗粒细胞（GC）的内质网应激信号通路。
结果：卵裂期的成熟率和优质胚胎率随着BLL的增加而显著下降。对于铅含量从低到高，活产率(68.29%，56.10%，39.02%；P=0.028）与BLL呈负相关。此外，高铅组卵泡液Pb水平和LDH水平明显高于低铅组。二项回归分析显示，BLL和活产率之间存在显著负相关(调整后的OR，0.38；95%CI，0.15-0.95，P=0.038）。进一步分析GCs的内质网应激(ER应激)信号通路发现,GRP78、总JNK、磷酸化JNK，随着BLLs的增加，CHOP增加，BCL-2减少。
结论：BLL与IVF患者的最终临床结局呈负相关，可能与ER应激反应和GC凋亡增加有关。因此，在IVF手术前减少铅暴露可能会提高最终成功率。
方法：本研究纳入了123名接受IVF周期的不孕妇女。所有参与者都被分成三个(低，中等,和高)由BLL三元率确定的组。促性腺激素释放激素（GnRH）激动剂方案用于所有患者的卵巢刺激，在取卵当天收集卵泡液。检测卵泡液中乳酸脱氢酶（LDH）水平和颗粒细胞（GC）的内质网应激信号通路。
结果：卵裂期的成熟率和优质胚胎率随着BLL的增加而显著下降。对于铅含量从低到高，活产率(68.29%，56.10%，39.02%；P=0.028）与BLL呈负相关。此外，高铅组卵泡液Pb水平和LDH水平明显高于低铅组。二项回归分析显示，BLL和活产率之间存在显著负相关(调整后的OR，0.38；95%CI，0.15-0.95，P=0.038）。进一步分析GCs的内质网应激(ER应激)信号通路发现,GRP78、总JNK、磷酸化JNK，随着BLLs的增加，CHOP增加，BCL-2减少。
结论：BLL与IVF患者的最终临床结局呈负相关，可能与ER应激反应和GC凋亡增加有关。因此，在IVF手术前减少铅暴露可能会提高最终成功率。
