Ketoconazole Contributes to Cryptorchidism Outcome Via Modulating Macrophage Trem2

Ketoconazole Contributes to Cryptorchidism Outcome Via Modulating Testicular Macrophage Trem2

Reduced hormone insulin-like 3, exclusively secreted by Leydig cells, has been identified as the recognized mechanism for cryptorchidism. Testicular macrophages residing in the testicular interstitium were thought to play a vital role in maintaining hormone secretion of Leydig cells. However, the contribution of macrophages to cryptorchidism remained poorly understood. Here, after 14 days of ketoconazole treatment, levels of both Trem2 and insulin-like 3 significantly decrease in human embryonic testes compared to the untreated control group. Conversely, 14 days of luteinizing hormone stimulation lead to elevated levels of Trem2 and insulin-like 3 in the testes compared to the untreated control group. Additionally, researchers find a positive correlation between Trem2 and insulin-like 3 expression in a human ex vivo tissue culture model. In summary, the study will propose Trem2 as a novel target for maintaining normal testicular descent by regulating the testicular immune microenvironment.

Study Overview

• Status: Recruiting
• Conditions: Cryptorchidism
• Intervention / Treatment: Drug: Ketoconazole; Drug: Luteinizing Hormone

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wenliang Ge; Phone Number: 13962854122; Email: gewl@ntu.edu.cn

Study Locations

• China
  • Jiangsu
    • Nantong, Jiangsu, China, 226001
      • Recruiting
      • Affiliated Hospital of Nantong University
      • Contact: Wenliang Ge, Dr; Phone Number: 13962854122; Email: gewl@ntu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1. Termination of pregnancy is not related to the health of the fetus.
• 2. The fetus is intact in development and free of malformations and abnormalities.
• 3. Estimation of gestational age based on parietal-rump length must be between 8 and 13 weeks of gestation.

Exclusion Criteria:

• 1. The termination of pregnancy is related to the health of the fetus
• 2. The fetus is not intact in development.
• 3. The fetus has malformations, abnormalities
• 4. Estimation of gestational age based on parietal-rump length must not be within 8-13 weeks of gestation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intact aborted fetal testicular tissue treated with ketoconazole; A fetal developmental stage is precisely determined. Then, fetal tissues are extracted for in vitro cultivation. Intact aborted fetal testicular tissues are cultured in a medium containing 10-6 mol/L ketoconazole, which is the injectable solution powder. Ketoconazole is administered starting on the first day and then every other day, for a total of 7 times over the 14-day in vitro culture period.	Drug: Ketoconazole; A fetal developmental stage is precisely determined. Then, fetal tissues are extracted for in vitro cultivation. Intact aborted fetal testicular tissues are cultured in a medium containing 10-6 mol/L ketoconazole, which is the injectable solution powder. Ketoconazole is administered starting on the first day and then every other day, for a total of 7 times over the 14-day in vitro culture period.
Experimental: Intact aborted fetal testicular tissue treated with luteinizing hormone; A fetal developmental stage is precisely determined. Then, fetal tissues are extracted for in vitro cultivation. Intact aborted fetal testicular tissues are cultured in a medium containing 1 IU/mL luteinizing hormone, which is the injectable solution powder. Luteinizing hormone is administered starting on the first day and then every other day, for a total of 7 times over the 14-day in vitro culture period.	Drug: Luteinizing Hormone; A fetal developmental stage is precisely determined. Then, fetal tissues are extracted for in vitro cultivation. Intact aborted fetal testicular tissues are cultured in a medium containing 1 IU/mL luteinizing hormone, which is the injectable solution powder. Luteinizing hormone is administered starting on the first day and then every other day, for a total of 7 times over the 14-day in vitro culture period.
No Intervention: Intact aborted fetal testicular tissue treated with none; A fetal developmental stage is precisely determined. Then, fetal tissues are extracted for in vitro cultivation. Intact aborted fetal testicular tissues are cultured in a medium.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative expression of Trem2 and insulin-like 3 protein	Ketoconazole promotes a decrease in Trem2 and a decrease in insulin-like 3, and they are strongly correlated.	The date of 14 days cultured

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University
• Investigators: Study Director: Wenliang Ge, Affiliated Hospital of Nantong University

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: cryptorchidism; Leydig cells; testicular macrophages; immune micro-environment
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Urogenital Abnormalities; Congenital Abnormalities; Testicular Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Cryptorchidism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Hormones; Ketoconazole
• Other Study ID Numbers: 82171587

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No