Abstract
Infertility affects 10 to 15% of couples worldwide, with a male factor contributing up to 50% of these cases. The primary tool for diagnosing male infertility is traditional semen analysis, which reveals sperm concentration, morphology, and motility. However, 25% of infertile men are diagnosed as normozoospermic, meaning that, in many cases, normal-appearing sperm fail to fertilize an egg. Thus, new information regarding the mechanisms by which sperm acquire fertilizing ability is needed to develop a clinically feasible test that can predict sperm function failure. An important feature of sperm fertilization capability in many species is plasma membrane hyperpolarization (membrane potential becoming more negative inside) in response to signals from the egg or female genital tract. In mice, this hyperpolarization is necessary for sperm to undergo the changes in motility (hyperactivation) and acrosomal exocytosis required to fertilize an egg. Human sperm also hyperpolarize during capacitation, but the physiological relevance of this event has not been determined. Here, we used flow cytometry combined with a voltage-sensitive fluorescent probe to measure absolute values of human sperm membrane potential. We found that hyperpolarization of human sperm plasma membrane correlated positively with fertilizing ability. Hyperpolarized human sperm had higher in vitro fertilization (IVF) ratios and higher percentages of acrosomal exocytosis and hyperactivated motility than depolarized sperm. We propose that measurements of human sperm membrane potential could be used to diagnose men with idiopathic infertility and predict IVF success in normozoospermic infertile patients. Patients with depolarized values could be guided toward intracytoplasmic sperm injection, preventing unnecessary cycles of intrauterine insemination or IVF. Conversely, patients with hyperpolarized values of sperm membrane potential could undergo only conventional IVF, avoiding the risks and costs associated with intracytoplasmic sperm injection.
Highlights
Infertility, defined as the inability of a couple to achieve pregnancy after 12 months of unprotected intercourse, affects between 10 and 15% of couples around the world (Sharma et al, 2013)
We found that human sperm membrane hyperpolarization correlated with sperm fertility capacity in in vitro fertilization (IVF) patients
MO); 3, 3 -dipropyl- thiadicarbocyanine iodide [DiSC3(5)] was from Invitrogen (Carlsbad, CA, United States); Hoechst 33342 was from Cayman Chemicals, (Ann Arbor, MI, United States); paraformaldehyde was from Electron Microscopy Sciences (Hatfield, PA, United States); Dulbecco’s Phosphate Buffered Saline (DPBS) was from GIBCO Life Technologies (Gaithersburg, MD, United States); and Quinn’s Advantage Human (HTF) fertilization media and human serum albumin were from CooperSurgical (Trumbull, CT, United States)
Summary
Infertility, defined as the inability of a couple to achieve pregnancy after 12 months of unprotected intercourse, affects between 10 and 15% of couples around the world (Sharma et al, 2013). Many such couples turn to in vitro fertilization (IVF), which has been used to conceive over 6.5 million babies. To diagnose these men, assisted reproduction specialists rely on semen analysis, which provides information about sperm concentration, morphology, and motility. Given that capacitation is required for fertilization, a test that could assess the ability of sperm to undergo this process could be a valuable addition to IVF diagnostics
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