Emilio Gómez

Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine

Human spermatozoa possess a specialized capacity to generate reactive oxygen species (ROS) that is thought to be of significance in the redox regulation of sperm capacitation (De Lamirande and Gagnon, 1993; Aitken et al., 1995). However, the mechanisms by which ROS are generated by these cells are not understood. In this study we have examined the possible significance of NADPH as a substrate for ROS production by human spermatozoa. Addition of NADPH to viable populations of motile spermatozoa induced a sudden dose‐dependent increase in the rate of superoxide generation via mechanisms that could not be disrupted by inhibitors of the mitochondrial electron transport chain (antimycin A, rotenone, carbonyl cyanide m‐chlorophenylhydrazone [CCCP], and sodium azide), diaphorase (dicoumarol) xanthine oxidase (allopurinol), or lactic acid dehydrogenase (sodium oxamate). However, NADPH‐induced ROS generation could be stimulated by permeabilization and was negatively correlated with sperm function. Both NADH and NADPH were active electron donors in this system, while NAD+ and NADP+ exhibited little activity. Stereospecificity was evident in the response in that only the β‐isomer of NADPH supported superoxide production. The involvement of a flavoprotein in the electron transfer process was indicated by the high sensitivity of the oxidase to inhibition by diphenylene iodonium and quinacrine. These results indicate that NAD(P)H can serve as an electron donor for superoxide generation by human spermatozoa and present a simple strategy for the production of motile populations of free radical generating cells with which to study the significance of these molecules in the control of normal and pathological sperm function. Mol. Reprod. Dev. 47:468–482, 1997.

Obesity and the risk of spontaneous abortion after oocyte donation.

OBJECTIVE To determine whether obesity increases the risk of spontaneous abortion. DESIGN Retrospective study. SETTING Oocyte donation program at the Instituto Valenciano de Infertilidad in Spain. PATIENT(S) Seven hundred twelve cycles of recipients of ovum donation with known body mass index (BMI), good-quality embryo transfer, and absence of uterine pathology or clinical history of antiphospholipid antibodies or recurrent abortion. INTERVENTION(S) Recipients were divided in four BMI (kg/m(2)) groups: lean, with BMI <20 (n = 92; 12.9%); normal, with BMI = 20-24.9 (n = 398; 55.9%); overweight, with BMI = 25-29.9 (n = 172; 24.2%); and obese, with BMI >/=30 (n = 50; 7%). Clinical parameters were compared among the groups. MAIN OUTCOME MEASURE(S) Spontaneous abortion rates according to BMI. RESULT(S) No difference was found among the four BMI groups in any of the parameters of the cycle analyzed. The overall abortion rate was 15.8% (57 of 360). There were significant differences in abortion rates between the obese (38.1%), and the normal (13.3%) and overweight (15.5%) groups. When several cutoff BMI values were established (20, 25, and 30), only the obese women demonstrated a greater risk of abortion. Compared with the normal population, the obese group showed a significant fourfold increase in the risk of spontaneous abortion. CONCLUSION(S) Our findings confirm that obesity (BMI >/=30) is an independent risk factor for spontaneous abortion. Therefore, it would be advisable for obese patients to reduce weight before becoming pregnant.