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Association between blood lead levels and unfavorable IVF outcomes: potential involvement of endoplasmic reticulum stress response in granulosa cells

  • Assisted Reproduction Technologies
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Abstract

Purpose

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.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AMH:

anti-Mullerian hormone

BCL-2:

B cell lymphoma-2

BLL:

blood lead level

BMI:

body mass index

CDC:

Center for Disease Control and Prevention of US

COH:

controlled ovarian hyperstimulation

CHOP:

C/EBP homologous protein

E2:

estrogen

ER:

endoplasmic reticulum

FF:

follicle fluid

FSH:

follicular-stimulating hormone

GRP78:

glucose regulated protein 78

GnRH:

gonadotropin-releasing hormone

GC:

granulosa cell

Gn:

gonadotropins

GM:

geometric mean

ICSI:

intracytoplasmic sperm injection

IQR:

median and interquartile range

IVF:

in vitro fertilization

JNK:

c-Jun N-terminal kinase

LDH:

lactate dehydrogenase

LH:

luteinizing hormone

P:

progesterone

PRL:

prolactin

T:

testosterone

WHO:

World Health Organization

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Funding

This work was supported by grants from Wenzhou City Science and Technology Bureau, CN (Y20220412) and Natural Science Foundation of Zhejiang Province, CN (Z23H040003, HC). These sources did not influence the study design, the collection, analysis or interpretation of data, or the writing of the paper.

Author information

Author notes

  1. Dan Shan and Yanning Lv contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China

    Dan Shan, Yanning Lv, Junzhao Zhao, Fan Zhang, Haitao Xi, Haifan Qiu, Jieqiang Lv & Haolin Chen

  2. Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Department of Pediatric Urology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China

    Haolin Chen

  3. Department of Pharmacology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China

    Haolin Chen

  4. Zhejiang Provincial Key Laboratory of Anesthesiology, Department of Anesthesiology, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China

    Haolin Chen

Authors
  1. Dan Shan
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Contributions

Dan Shan and Yanning Lv: Conceptualization, Investigation, Methodology, Formal analysis, Data curation, Visualization, Writing – original draft. Junzhao Zhao, Fan zhang, Haitao Xi, Haifan Qiu: Methodology, Formal analysis, Validation. Jieqiang Lv: Conceptualization, Methodology, Project administration, Writing – review. Haolin Chen: Conceptualization, Methodology, Supervision, Project administration, Funding acquisition, Writing – review and editing.

Corresponding authors

Correspondence to Jieqiang Lv or Haolin Chen.

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Shan, D., Lv, Y., Zhao, J. et al. Association between blood lead levels and unfavorable IVF outcomes: potential involvement of endoplasmic reticulum stress response in granulosa cells. J Assist Reprod Genet 41, 947–956 (2024). https://doi.org/10.1007/s10815-024-03056-2

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