Altered three-dimensional organization of sperm genome in DPY19L2-deficient globozoospermic patients.

PURPOSE: To explore the three-dimensional (3D) organization of sperm genome in DPY19L2-deficient globozoospermic patients speculating a link between DPY19L2 and genome organization of sperm nucleus. METHODS: This is a study of chromatin organization in DPY19L2-deficient globozoospermic patients and healthy donors using three-dimensional fluorescence in situ hybridization (3D-FISH) combined with confocal laser scanning microscopy followed by 3D image analysis. The 3D structures of sperm nuclei, chromocenter, telomeric regions and chromosome territories (CTs), were reconstructed using IMARIS software, and the relative radial position for each individual signal was calculated. Statistical analysis used a non-parametric Mann-Whitney test was appropriate with significance at p < 0.05. RESULTS: DPY19L2-deficient globozoospermic patients display impaired sperm chromocenter organization resulting in an increased number of chromocenters (5.4 vs 3.5; p < 0.0001). Moreover, radial positions of telomeres are modified with a more central position in globozoospermic nuclei. 3D-FISH analysis of five chromosome territories (CTs) (X, Y, 7, 17, 18) showed that DPY19L2-deficient globozoospermic sperm nuclei display altered spatial organization of CT X, CT 7 and CT 18. CONCLUSIONS: Our findings strengthen the hypothesis that DPY19L2 might be considered as a LINC-like protein having a crucial role in the organization of nuclear chromatin in sperm nucleus through its interaction with nuclear lamina. Our results might also explain defective embryonic development after intracytoplasmic sperm injection (ICSI) performed with DPY19L2-deficient globozoospermic sperm.

Neoadjuvant gonadotropin-releasing hormone therapy before surgery and effect on fertility index in unilateral undescended testes: a prospective randomized trial.

OBJECTIVES: To investigate, in a prospectively randomized trial, whether preoperative gonadotropin-releasing hormone (GnRH) therapy improves the fertility index in primary cryptorchidism. Cryptorchidism is a common condition with a high risk of infertility. Treatment with GnRH appears to improve fertility later in life by inducing germ cell maturation. METHODS: A total of 24 boys, 12-123 months old (median 34.5), with 24 undescended testes were prospectively assigned to 2 groups during a 24-month period. The patients were randomized to receive either orchiopexy alone (n = 12) or orchiopexy combined with neoadjuvant GnRH therapy (n = 12) as a nasal spray for 4 weeks at 1.2 mg/d. In both groups, testicular biopsies were performed at orchiopexy, and the histopathologic fertility index was determined. RESULTS: The mean fertility index in the group treated with GnRH before surgery was significantly greater (0.88 +/- 0.31) than in the group without hormonal stimulation (0.49 +/- 0.52; P = .02). No significant correlation was found between the fertility index in the GnRH group and the patient's age. CONCLUSIONS: The results of our study have shown that neoadjuvant GnRH treatment improves the fertility index in prepubertal cryptorchidism and, consequently, should improve fertility in adulthood.