D.J. Raburn

Regulation of the macrophage population in postnatal rat testis

Testicular macrophages increase in concentration during postnatal development in rats. This process may be under hormonal control since administration of hCG stimulates a similar increase to occur precociously. The purpose of the present studies was to determine how the macrophage population is regulated during normal postnatal development and in response to exogenous hCG. We first determined that testicular macrophages proliferate in situ during development and that hCG administration results in an increase in proliferation when given to 10-day-old rats. We next evaluated whether hCG might exert its effects through enhanced secretion of testosterone from Leydig cells. We found that testosterone could not induce a precocious increment in the macrophage concentration when it was administered to newborn pups for 10 days. Finally, the normal increase in macrophage concentration that occurs prior to puberty could not be blocked by treatment with the antiandrogen Casodex. The results are consistent with the hypothesis that the macrophage population expands by proliferation, perhaps under gonadotropin control. In addition, neither the precocial expansion that occurs in response to hCG nor the normal expansion that occurs before puberty is mediated by testosterone.

Antiretroviral Therapy Effects on Genetic and Morphologic End Points in Lymphocytes and Sperm of Men with Human Immunodeficiency Virus Infection

Many human immunodeficiency virus (HIV)-infected persons receive prolonged treatment with DNA-reactive antiretroviral drugs. A prospective study was conducted of 26 HIV-infected men who provided samples before treatment and at multiple times after beginning treatment, to investigate effects of antiretrovirals on lymphocyte and sperm chromosomes and semen quality. Several antiretroviral regimens, all including a nucleoside component, were used. Lymphocyte metaphase analysis and sperm fluorescence in situ hybridization were used for cytogenetic studies. Semen analyses included conventional parameters (volume, concentration, viability, motility, and morphology). No significant effects on cytogenetic parameters, semen volume, or sperm concentration were detected. However, there were significant improvements in sperm motility for men with study entry CD4 cell counts >200 cells/mm(3), sperm morphology for men with entry CD4 cell counts < or =200 cells/mm(3), and the percentage of viable sperm in both groups. These findings suggest that nucleoside-containing antiretrovirals administered via recommended protocols do not induce chromosomal changes in lymphocytes or sperm but may produce improvements in semen quality.

Redefining the Relationship Between Sperm Deoxyribonucleic Acid Fragmentation as Measured by the Sperm Chromatin Structure Assay and Outcomes of Assisted Reproductive Techniques

OBJECTIVE To test the hypothesis that couples with sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI) values >27% would not achieve pregnancy with assisted reproductive techniques (ART) and to investigate how DFI and high DNA stainability (HDS), as measured by the SCSA, affect fertilization, cleavage, implantation, and pregnancy rates in IVF cycles. DESIGN Prospective clinical study. SETTING Academic human reproduction laboratory. PATIENT(S) One hundred couples undergoing IVF with conventional insemination or intracytoplasmic sperm injection. INTERVENTION(S) Testing with SCSA was performed by SCSA Diagnostics (Brookings, South Dakota) on a semen aliquot taken from ejaculate used for ART. MAIN OUTCOME MEASURE(S) Relating total DFI and HDS to conventional semen parameters and cycle-specific outcomes after ART. RESULT(S) Nine of nineteen couples achieved clinical pregnancy when DFI was > or =27%, and 2 of 22 couples achieved clinical pregnancy when DFI was < or =9%. One of nine couples achieved clinical pregnancy with HDS >17%. The DFI was negatively correlated with sperm density (r = -0.23, P<.03) and motility (r = -0.55, P<.00), and HDS was negatively correlated with sperm density (r = -0.37, P<.00). CONCLUSION(S) Sperm chromatin structure assay failed to identify elevated DFI thresholds for negative pregnancy outcome after ART. Patients with low DFI (< or =9%) were least likely to become pregnant, which is also contradictory to SCSA marketing, which states that DFIs of < or =15% have excellent fertility potential. Patients with HDS > or =17% had low pregnancy rates, indicating decreased fertility potential, which deserves further investigation. Larger studies are necessary to confirm that low DFI is associated with decreased fertility and, if proved, might redefine the use of the SCSA in evaluating infertility.