Yu Sheng Cheng

Clinical Characteristics and Reproductive Outcomes in Infertile Men With Testicular Early and Late Maturation Arrest

OBJECTIVE To compare the clinical characteristics and reproductive outcomes of nonobstructive azoospermic men with uniform early and late maturation arrest. METHODS Patients with biopsy-documented uniform maturation arrest undergoing testicular sperm retrieval and complete medical records were enrolled in the present study. Their medical history, physical examination findings, testicular volume, serum hormone parameters, genetic anomalies, sperm retrieval, and reproductive outcomes were retrospectively analyzed. RESULTS In a cohort of 223 nonobstructive azoospermic men, 34 men with uniform maturation arrest (21 early maturation arrest and 13 late maturation arrest) were identified. No significant differences were seen in the age distribution, testicular volume, or hormone parameters between patients with early and late maturation arrest. Only 13 patients (38.2%) had a normal serum follicle-stimulating hormone level and normal testicular volume. Patients with early maturation arrest had a greater frequency of overall genetic anomalies, and patients with late maturation arrest had a greater frequency of previous testicular insults. The sperm retrieval and impregnation rate were nonsignificantly greater in patients with late maturation arrest. CONCLUSION Maturation arrest has a variety of causes and presents with diverse phenotypes. Not all patients with uniform maturation arrest have a normal follicle-stimulating hormone level or testicular volume. Patients with early maturation arrest have a greater incidence of genetic anomalies and are more likely to have worse reproductive outcomes than are patients with late maturation arrest.

Association of aberrant expression of sex-determining gene fibroblast growth factor 9 with Sertoli cell–only syndrome

OBJECTIVE To investigate the expressions of fibroblast growth factor 9 (FGF9) in normal testes and in testes with Sertoli cell-only syndrome (SCOS), explore the biological function of testicular FGF9, and identify the sequence variants of FGF9 gene in patients with SCOS. DESIGN Retrospective case study. SETTING University reproductive clinic. PATIENT(S) Forty-one patients with SCOS, seven with normal spermatogenesis, and 100 controls. INTERVENTION(S) Protein expressions of testicular FGF9 and sequence variants of FGF9 gene in normal controls and patients with SCOS were studied. The biological function and regulation of testicular FGF9 were assessed in vitro. MAIN OUTCOME MEASURE(S) Expression profiles of testicular FGF9, effects of FGF9 on germ cell proliferation, and sequence variants of the FGF9 gene. RESULT(S) FGF9 was predominately expressed in the cytoplasm of Leydig cells of normal testis; its expression was significantly decreased in patients with SCOS. Conditioned medium of FGF9-treated Leydig cells stimulated germ cell proliferation. A promoter polymorphism (c.-712C→T) of the FGF9 gene attenuated the promoter activity, which contributes to one of the causes of its low expression. CONCLUSION(S) In addition to the role of sex determination, FGF9 is expressed in postnatal Leydig cells and is involved in cell-to-cell interaction of testicular function. Aberrant expression of testicular FGF9 is associated with SCOS.

Causes and Clinical Features of Infertile Men With Nonobstructive Azoospermia and Histopathologic Diagnosis of Hypospermatogenesis

OBJECTIVE To analyze the causes and the clinical features of infertile men with nonobstructive azoospermia and hypospermatogenesis (HS). MATERIALS AND METHODS This retrospective cohort study included 100 patients with nonobstructive azoospermia and HS and 8 patients with obstructive azoospermia and normal spermatogenesis. The severity of HS was subdivided into 3 groups (mild, moderate, and severe) based on spermatogenic score. Data of history, physical findings, serum hormone profiles, genetic studies, and sperm retrieval rate were collected. Whole genome DNA methylation analysis and microarray mRNA expression analysis were used to identify the candidate genes of methylation dysregulation in HS. RESULTS Thirty-two (32%) patients had at least 1 prior/current testicular insults and 13 (13%) patients had genetic anomalies. Fifty-five (55%) patients were categorized as idiopathic HS. Patients with mild HS had a higher frequency of testicular insults, and patients with severe HS had a significantly higher frequency of genetic anomalies. Sperm retrieval rate was 100%, 100%, and 88.4% for patients with mild, moderate, and severe HS, respectively. Four sterility-related genes, including BOLL, DDX4, HORMAD1, and MAEL, were found to have increased methylation at CpGs of the promoter regions and decreased mRNA expressions in HS testis. CONCLUSION The causes of HS are complex and multifactorial. The main causes of HS were prior or current testicular insults and chromosomal or genetic anomalies. More than half of the patients were categorized as idiopathic HS. With high throughput analysis, methylation dysregulations of BOLL, DDX4, HORMAD1, and MAEL are believed to be associated with HS.