Ketoconazole Contributes to Cryptorchidism Outcome Via Modulating Macrophage Trem2

Affiliated Hospital of Nantong University10 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Cryptorchidism

Interventions

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.

Luteinizing HormoneDRUG

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.

Eligibility

Sex: MALEMin age: 8 WeeksMax age: 13 WeeksHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: The date of 14 days cultured