TY - JOUR
T1 - Membrane Potential Determined by Flow Cytometry Predicts Fertilizing Ability of Human Sperm
AU - Molina, Lis C.Puga
AU - Gunderson, Stephanie
AU - Riley, Joan
AU - Lybaert, Pascal
AU - Borrego-Alvarez, Aluet
AU - Jungheim, Emily S.
AU - Santi, Celia M.
N1 - Publisher Copyright:
© Copyright © 2020 Puga Molina, Gunderson, Riley, Lybaert, Borrego-Alvarez, Jungheim and Santi.
PY - 2020/1/21
Y1 - 2020/1/21
N2 - 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.
AB - 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.
KW - IVF
KW - capacitation
KW - flow cytometry
KW - human
KW - membrane potential
KW - normozoospermic infertility
KW - sperm
UR - http://www.scopus.com/inward/record.url?scp=85079014371&partnerID=8YFLogxK
U2 - 10.3389/fcell.2019.00387
DO - 10.3389/fcell.2019.00387
M3 - Article
C2 - 32039203
AN - SCOPUS:85079014371
SN - 2296-634X
VL - 7
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 387
ER -