Biological basis for human capacitation—revisited

Human Reproduction Update, Vol.23, No.3 pp. 289–299, 2017 Advanced Access publication on January 23, 2017 doi:10.1093/humupd/dmw048 Biological basis for human capacitation —revisited Christopher De Jonge* Andrology Program, University of Minnesota Medical Center, 606 24th Avenue South, Suite 525, Minneapolis, MN 55454, USA Department of Urology, University of Minnesota, Minneapolis, MN 55454, USA *Correspondence address. Andrology Program, University of Minnesota Medical Center, 606 24th Avenue South, Suite 525, Minneapolis, MN 55454, USA. E-mail: Submitted on October 14, 2016; resubmitted on December 21, 2016; editorial decision on December 30, 2016; accepted on January 3, 2017 TABLE OF CONTENTS ........................................................................................................................... • Introduction • Methods • Results Historical perspective Will the real ‘capacitation’ please stand up? Conundrums and considerations • Closing comments BACKGROUND: A little more than a decade ago a review entitled ‘Biological basis for human capacitation’ was published. A primary conclusion of the review was that with all the technological advances that have been made since the first experiments demonstrated the in vivo requirement of capacitation for fertilization, very little progress had since been made, most significantly for human. OBJECTIVE AND RATIONALE: The present review was carried out to provide an update on the biological basis for human capacita- tion. It briefly revisits the original schema, presents a review of the literature that urged research interest in human sperm capacitation and puts under the spotlight the original definition of capacitation balanced against the limitations of experiments in vitro to characterize a complex process that necessarily mandates a female component, and very recent findings in the mouse. It also includes proposed considerations for new thinking regarding capacitation, and progress toward understanding the biology of human capacitation. SEARCH METHODS: The PubMed, Google Scholar and Scopus literature databases were reviewed extensively using inclusive, broad and multispecies search terms without publication date limitation. OUTCOMES: Comprehensive screening of the literature database showed that no papers regarding human sperm capacitation in vivo have been published in the past 20 years. Recent experiments in the mouse have provided compelling and unanticipated data regarding capacitation and in vivo fertilization. Questions were posed and addressed regarding: stimuli for initiation of capacitation, capacitation relative to the cumulus–oocyte complex, comparison between in vivo and in vitro capacitation, and potential species-specific differences in location and timing of capacitation. WIDER IMPLICATIONS: There has been no progress on the in vivo biology of human sperm capacitation since before the turn of the century. Human IVF and its technologies may likely have inhibited, and continue to hold back, any future in vivo experiments that would address one or more questions regarding acquisition of fertilizing capacity in human. The limiting factor for progress in the area is access to funding and human subjects. Key words: female tract / male tract / fertilization / capacitation / in vivo / semen / sperm transport © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: 290 Introduction A little more than a decade ago the review ‘Biological basis for human capacitation’ was published (De Jonge, 2005). The review relied primarily on human in vitro and a paucity of in vivo data to construct a hypothetical framework for the biological factors and processes that possibly contribute to capacitation of human spermatozoa in vivo. The current review briefly revisits the original schema, presents a review of the literature that urged research interest in human sperm capacitation, and puts into spotlight the original definition of capacitation balanced against the limitations of experiments in vitro to characterize a complex process that necessarily mandates a female component, and very recent findings in the mouse. It also includes proposed considerations for new thinking regarding capacitation, and progress toward understanding the biology of human capacitation. Before embarking on our new journey it is purposeful to revisit the origin and definition of the term ‘capacitation’. ‘Austin (1951, 1952) and Chang (1951) independently described changes that are prerequisite for non-human mammalian spermatozoa to fertilize oocytes in vivo, described as the acquisition of ‘fertilizing capacity’. This acquisition process was termed ‘capacitation’ and is defined as, ‘…the sperm must undergo some form of physiological change or capacitation before it is capable of penetrating the egg’ (Austin, 1952). The definition was later expanded by Austin and Bishop (1958) to include ‘residence of spermatozoa in the female reproductive tract to become capacitated’. To gain understanding of the molecular processes currently purported to play a role in mammalian sperm capacitation, readers are encouraged to investigate recent reviews (e.g. Gervasi and Visconti, 2016; Jin and Yang, 2016). Methods The PubMed, Google Scholar and Scopus literature databases were reviewed extensively using inclusive, broad and multispecies search terms without publication date limitation. Results A brief review of ‘Biological Basis for Human Capacitation’ (see De Jonge, 2005 for complete details and references). An evidence-derived proposal for the biological (in vivo) process of human sperm capacitation was framed by De Jonge (Fig. 1, De Jonge, 2005). In the review, it was put forth that a heterogeneous sperm population is deposited into the vagina and within a very short time (~90 s) progressively motile sperm migrate into the periovulatory, hormonally primed cervical mucus. The mucus contributes to initiating capacitation by changing not only the composition of the sperm population but also sperm membrane biochemistry. The arrangement of mucins in the mucus serves to support passage of the healthy, motile sperm while trapping or inhibiting those in poor functional (e.g. motility) and/or structural condition. A requisite for capacitation is the removal of sperm membrane cholesterol that consequently contributes to increased sperm plasma membrane fluidity, and some evidence supports initiation of that removal possibly by mucus ultrastructural and compositional elements. Reactive oxygen species De Jonge (ROS) produced by leukocytes infiltrating into the post-coital mucus contribute both positively and negatively to the migrating sperm population. ROS have a priming influence on capacitation in normally functioning sperm. In contrast, ROS have a deleterious influence on poorly functioning and immature sperm. Thus, it can be said th (...truncated)