Effects of Phthalate Exposure on the Hand Digit (2D4D) Ratio, Puberty Onset and Its Underlying Mechanism in 14- to 17-Year-Old Children

2023 Fiscal Year Research-status Report

• Project/Area Number: 23K19884
• Research Institution: Hokkaido University
• Principal Investigator: MEGASARI MARSELA 北海道大学, 保健科学研究院, 博士研究員 (60978914)
• Project Period (FY): 2023-08-31 – 2025-03-31
• Keywords: Phtalate exposure / Children / Birth cohort / Puberty Onset / Hand Digit (2D4D) Ratio

Outline of Annual Research Achievements

The aim of this study is to evaluate the effects of phthalates exposure during 7 years of age on children aged 14-17 years old in the Hokkaido Study, specifically on; (a) puberty onset, (b) alteration of 2D4D ratio, 1) reproductive hormones, (2) IGF-1, and (3) osteocalcin biomarkers. During the initial three months, I established research ethics protocols at the Faculty of Sciences, Hokkaido University. Following this, I conducted an opt-out procedure to publicly disclose my research at the Center for Environmental and Health Sciences (CEHS), Hokkaido University. After obtaining ethical approval, I conducted a preliminary data analysis study, revealing that the highest concentration of phthalate metabolites was found in MnBP (Median: 31.0 ng/ml). The average 2D:4D ratio showed no significant correlation with prenatal phthalate metabolites in either boys or girls. An inverse relationship was observed between log MiBP concentrations and log INSL3 concentrations in boys, with a regression coefficient (β) of -0.246 and a 95% confidence interval (CI) of -0.392 to -0.100 (p=0.001). There was no significant mediating effect of 2D:4D on the association between phthalates and hormones. Based on these findings, I submitted and was accepted to present at The International Society for Environmental Epidemiology Asia and Western Pacific Chapter (ISEE-AWPC) and International Society for Exposure Science Asia Chapter (ISES-AC) Joint Conference 2024, scheduled for June in Malaysia.

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

In the past 6 months, I have completed the research ethics procedure, research opt-out, and preliminary study. Subsequently, I applied for and was accepted to a conference. Those all accounted for 50% of my research project. For the remaining tasks, I need to finalize the measurement of reproductive hormones, IGF1, and osteocalcin biomarkers. I will conduct a comprehensive statistical analysis and prepare the research publication. Reflecting on my current progress, I believe I am on track to meet the project timeline and finish by March 2025.This fine progress is largely due to the support of my supervisor and lab members, who have facilitated the smooth execution of research procedures. Furthermore, I received assistance from researchers at CEHS, ensuring that everything proceeded as planned. Within our lab, we hold weekly meetings to share progress and address any research challenges. Additionally, we participate in CEHS meetings, engaging with researchers from outside our laboratory. Their diverse perspectives and expertise significantly contribute to enhancing the quality of my research.

Strategy for Future Research Activity

I have been accepted to present at the ISEE-AWPC and ISES-AC 2024 conference, and I will be attending in June 2024. Following this, my next steps involve conducting measurements for reproductive hormones, IGF1, and osteocalcin biomarkers, starting in May 2024. I will utilize the Bio-Plex Multiplex assay for IGF-1 and osteocalcin biomarkers, while I will employ ELISA testing for reproductive hormones. Once data collection is complete, I will perform a comprehensive statistical analysis. Subsequently, I will prepare the manuscript for submission to a high-impact journal. Additionally, I plan to participate in the 95th Conference of the Japanese Society of Hygiene in March 2025.

Causes of Carryover

My reasons for incurring amount to be used next fiscal year are because during this period I focus on the preliminary study including preliminary analysis and conference preparation to share my preliminary result. Conducting this preliminary study is essential to properly guide my research into the right direction Next, I plan to allocate the budget towards conducting measurements of reproductive hormones, IGF1, and osteocalcin biomarkers. Specifically, in May 2024, I will procure The Bioplex Multiplex Assay kits. I will utilize the budget to cover my transportation expenses and accommodation for my participation in the 95th Conference of the Japanese Society of Hygiene in March 2025. The remaining budget will be allocated for publication purposes, including English proofreading and submission fees for high-impact journals. For all these expenses, I will utilize the remaining total budget of 1,888,480 yen by the end of this fiscal year, which concludes in March 2025, in accordance with my research timeline.