Expression of cell surface CD9 in fertile and infertile women

Abstract

CD9 is a cell surface protein that plays a crucial role in mouse sperm-oocyte fusion. We compared the CD9 expression levels on human platelets in women with unexplained infertility vs. age, weight, and race-matched fertile women. In in vitro fertilization (IVF) patients, we also compared platelet CD9 levels to fertilization rates. Prospective, observational, cohort study of women with unexplained infertility as compared to fertile women. Twenty women with unexplained infertility ages 26–43 were recruited from an academic fertility clinic. Each study subject demonstrated positive ovulatory function, normal ovarian reserve, patent fallopian tubes, and a normal semen analysis from the male partner. Twenty women with demonstrated fertility were recruited as control subjects. Each control subject had at least one liveborn offspring and no history of infertility or use of fertility drugs. Subjects were matched one to one to a control within 2 years of age, 1.5 kg/m2 of BMI, and by race. From each study subject and control, platelet CD9 expression was evaluated by flow cytometry. Fertilization rates of the study subjects who underwent IVF were calculated and compared to corresponding CD9 levels. Infertile patients (mean 113.2 MFI ± 38) demonstrated higher CD9 levels than the fertile controls (mean 99.5 MFI ± 25) though this was not statistically significant (p = 0.120). Using linear regression analysis, there was an inverse relationship between CD9 levels and fertilization rates of the 12 IVF patients (r = -0.6547, p = 0.0209). CD9 levels of infertile patients were increased over that of fertile patients though not statistically significant. Studies by Le Naour et al. with female CD9 knockout mice showed decreased fertility rates. Contrary to this, our study, using platelets as a cell surrogate for oocytes, revealed higher CD9 levels in infertile patients. Furthermore, the IVF patients with higher CD9 levels had decreased fertilization rates. Our data suggest that the high CD9 expression may have a negative effect on fertility via competition, as may decreased levels, ultimately affecting the efficiency of sperm-egg fusion. If so, we would expect infertile patients with abnormal CD9 levels to have improved fertilization rates by eliminating sperm-egg fusion via intracytoplasmic sperm injection (ICSI). Our study suggests that CD9 may play a crucial role in unexplained human infertility.