Susan S Suarez

• MS, PhD
• Professor Emeritus at Cornell University

To fertilize eggs, sperm must pass through narrow, complex channels filled with viscoelastic fluids in the female reproductive tract. While it is known that the topography of the surfaces plays a role in guiding sperm movement, sperm have been thought of as swimmers, i.e., their motility comes solely from sperm interaction with the surrounding flui...

To fertilize eggs, sperm must pass through narrow, complex channels filled with viscoelastic fluids in the female reproductive tract. While it is known that the topography of the surfaces plays a role in guiding sperm movement, sperm have been thought of as swimmers, i.e., their motility comes solely from sperm interaction with the surrounding flui...

Interactions between sperm and the female reproductive tract (FRT) are complex, in many cases poorly understood, and likely to contribute to the mechanistic basis of idiopathic infertility. As such, it is not surprising that the FRT was often viewed historically as a “hostile” environment for sperm. The FRT has also been touted as a selective envir...

Collective swimming is evident in the sperm of several mammalian species. In bull (Bos taurus) sperm, high viscoelasticity of the surrounding fluid induces the sperm to form dynamic clusters. Sperm within the clusters swim closely together and align in the same direction, yet the clusters are dynamic because individual sperm swim into and out of th...

During the passage through the female reproductive tract, sperm interact with various compartments and their immune systems. The immune system that protects the female against pathogens also could destroy sperm or prevent them from reaching the site of fertilisation. In particular, the uterine innate immune response is crucial from the perspectives...

Significance Mammalian sperm migration within the female reproductive tract requires navigational mechanisms, through which sperm respond to biophysical and biochemical cues. Previous studies revealed that biophysical cues for sperm in the female reproductive tract include fluid flow, wall architecture, and temperature gradients. Here, by exploring...

Evaluation of sperm motility is well-established in farm animals for quickly selecting ejaculates for semen processing into insemination doses and for evaluating the quality of preserved semen. Likewise, sperm motility is a fundamental parameter used by spermatologists in basic and applied science. Motility is commonly assessed using computer-assis...

The functions of the female reproductive tract not only encompass sperm migration, storage, and fertilization, but also support the transport and development of the fertilized egg through to the birth of offspring. Further, because the tract is open to the external environment, it must also provide protection against invasive pathogens. In biophysi...

We previously reported that sperm binding to cultured bovine oviduct epithelial cells induces an anti-inflammatory immune response. Now we have developed a differentiated explant model to focus on the oviductal ampulla, where fertilization occurs, and to study the effect of sperm capacitation on the immune response. We used heparin to stimulate bov...

The cover depicts a scanning electron micrograph of bull sperm that entered and remained within pre-ovulatory phase uterine glands in the sperm-endometrial explant co-culture model. Subsequently, polymorphonuclear neutrophils appeared to bind to sperm at the opening of the uterine glands. This local interaction between sperm and neutrophils in the...

We previously reported that sperm binding to cultured monolayers of bovine uterine epithelial cells induces an acute inflammatory response involving the Toll-like receptor (TLR2) signaling pathway. This response serves to clear the uterus of sperm and thereby prepares the endometrium for implantation. The endometrium is lined by surface epithelial...

Sperm interaction with the uterus and subsequent immune responses by the endometrium to remove excess, defective and dead sperm are important to prepare the endometrium for embryo implantation. We have recently developed a bovine ex-vivo explant culture model to study the link between sperm interaction with endometrium and immune responses. It was...

The moment of the fertilization of an egg by a spermatozoon—the point of “sperm success”- is a key milestone in the biology of sexually reproducing species and is a fundamental requirement for offspring production. Fertilization also represents the culmination of a suite of sexually selected processes in both sexes and is commonly used as a landmar...

The uterus has a well-developed innate immune system that recognizes microbes and sperm. We have recently shown that sperm binding to bovine uterine epithelial cells (BUEC) induces acute inflammatory response. This raises the query of whether the uterus uses a common or similar mucosal immune response to sperm and microbes; however, immune cross-ta...

Recent studies indicate that communication between the bovine embryo and the mother begins in the oviduct. Here, we aimed to investigate the effect of embryos on bovine oviducts for their immune responses using an in vitro model. First, zygotes were cultured with or without bovine oviduct epithelial cells (BOECs) for 4 days, when embryos had reache...

From flocking birds to swarming insects, interactions of organisms large and small lead to the emergence of collective dynamics. Here, we report striking collective swimming of bovine sperm in dynamic clusters, enabled by the viscoelasticity of the fluid. Sperm oriented in the same direction within each cluster, and cluster size and cell-cell align...

This revised and updated second edition provides a comprehensive account of the human male gamete. Detailed overviews of human sperm production, maturation, and function - and how these processes affect and influence fertility, infertility, and assisted reproduction - are given. A wide range of new developments including proteomics, spermatogenesis...

The influence of the hedgehog signaling pathway on reproduction was studied in transgenic mice in which a dominant active allele of the hedgehog signal transducer, smoothened (Smo), was conditionally expressed in the developing Müllerian duct and gonads through recombination mediated by anti-Müllerian hormone receptor 2-cre (Amhr2 cre ). Previous s...

In mammals, many sperm that reach the oviduct are held in a reservoir by binding to epithelium. To leave the reservoir, sperm detach from the epithelium; however, they may bind and detach again as they ascend into the ampulla toward oocytes. In order to elucidate the nature of binding interactions along the oviduct, we compared the effects of burst...

Microfluidics technology offers us an opportunity to model the biophysical and biochemical environments encountered by sperm moving through the female reproductive tract and, at the same time, to study sperm swimming dynamics at a quantitative level. In humans, coitus results in the deposition of sperm in the vagina at the entrance to the cervix. C...

The mammalian female reproductive tract interacts with sperm in various ways in order to facilitate sperm migration to the egg while impeding migrations of pathogens into the tract, to keep sperm alive during the time between mating and ovulation, and to select the fittest sperm for fertilization. The two main types of interactions are physical and...

The mouse is an established and popular animal model for studying reproductive biology. Epididymal mouse sperm, which lack exposure to secretions of male accessory glands and do not precisely represent ejaculated sperm for the study of sperm functions, have been almost exclusively used in studies. We compared ejaculated and epididymal sperm in an i...

Significance Mammalian females must selectively allow sperm with normal morphology and motility to ascend the reproductive tract while rejecting invasion of pathogens. By using microfluidic modeling, we revealed that microgrooves and gentle fluid flows, two major biophysical characteristics of the female tract, synergistically provide preferential...

We demonstrate that upstream swimming of sperm emerges via an orientation disorder-order transition. The order parameter, the average orientation of the sperm head against the flow, follows a 0.5 power law with the deviation from the critical flow shear rate (gamma - gamma(c)). This transition is successfully explained by a hydrodynamic bifurcation...

Egg and sperm have, understandably, been the "stars" of mammalian fertilization biology, particularly because artificial reproductive technologies allow for fertilization to occur outside of the female reproductive tract without other apparent contributions from either sex. Yet, recent research, including an exciting new paper, reveals unexpected a...

Aberrant sperm phenotypes coincide with the expression of unique sperm surface determinants that can be probed by objective, biomarker-based semen analysis and targeted as ligands for semen purification. This study evaluated a nanoparticle based magnetic purification method that removes defective spermatozoa (~30% of sample) from bull semen and imp...

Successful reproduction in mammals requires sperm to swim against a fluid flow and through the long and complex female reproductive tract before reaching the egg in the oviduct. Millions of them do not make it. Despite their clinical importance, the roles played in sperm migration by the diverse biophysical and biochemical microenvironments within...

Artificial insemination with frozen semen allows affordable, worldwide dissemination of gametes with superior genetics. Nevertheless, sperm are damaged by the cryopreservation process. Elucidating the molecular effects of cryopreservation on sperm could suggest methods for improving fertility of frozen/thawed semen. This study was undertaken to exa...

Chemotaxis refers to a process whereby cells move up or down a chemical gradient. Sperm chemotaxis is known to be a strategy exploited by marine invertebrates such as sea urchins to reach eggs efficiently in moving water. Less is understood about how or whether chemotaxis is used by mammalian sperm to reach eggs, where fertilization takes place wit...

Drawing for the simulation model. The dimension of the computation frame was 10 mm wide along x′ axis and 1 mm high along z′ axis and the channel size was 400 μm wide and 167 μm high with a 250 μm gap. The dashed line indicates the middle plane of the center channel where sperm motion was imaged, which is 83 μm from the bottom. Please note that the...

Comparison of gradient establishment between experiments (A) and computer simulation (B). The experimental results were obtained by re-plotting fluorescence of FITC-dextran (4 kDa) from Fig. 1. The simulation results were evaluated along with the same channel area at a half of the channel height (z′ = 83 μm, or dashed line in Fig. S1). Each colored...

Concentration profiles across the area of interests in the center channel during the experiment time period. A and B: The time evolution of resact concentration profiles in the first 38 s across the middle section (300 µm) of the center channel where the sea urchin sperm motion was analyzed. The time interval between lines was 2 s. The perfused con...

Sea urchin sperm swimming in a microfluidic channel in the absence of resact (Control). Sperm seeding density is 8×106 /ml. Each image has a size of 400 µm ×200 µm. The video is played in real time at 25 fps. Duration of the video is 19 s. (AVI)

The text describes the detailed work of the simulation of concentration profiles. (DOCX)

Sea urchin sperm swimming in center channel when 250 nM resact and medium were pumped through the source and sink channels, respectively, starting at time 0. Sperm seeding density is 120×106/ml. Each image has a size of 400 µm ×200 µm. The video plays at 10 fps and 5 times faster than real time. Initially, the resact diffused from the right to the...

Mouse sperm swimming in a microfluidic channel in the absence of progesterone. Sperm seeding density is 10×106 /ml. Each image has a size of 400 µm ×200 µm. The video is played in real time at 25 fps. Duration of the video is 19 s. (AVI)

Sea urchin sperm swimming in the center channel when 10 nM reseact solution and medium were pumped through the source and sink channels, respectively, starting at t = 0. Sperm seeding density is 8×106 /ml. Each image has a size of 400 µm ×200 µm. The video is played in real time at 25 fps. The resact is diffusing from left to the right in the centr...

Mouse sperm swimming in the center channel when 250 µM progesterone and medium were pumped through the source and sink channels, respectively, starting at time 0. Sperm seeding density is 10×106 /ml. Each image has a size of 400 µm ×200 µm. The video is played in real time at 25 fps. The progesterone is diffusing from the left to the right side of...

Infertility is a significant issue, both for humans and dairy cattle. In order for fertilization to happen, sperm must migrate through the female reproductive tract to reach the egg in the oviduct (fallopian tube). There is strong evidence that sperm interact with the female tract via both chemical and physical mechanisms. In this work, we focus on...

Cryopreserved semen is used widely in the dairy industry to inseminate cows. This practice has allowed the affordable dissemination of semen from superior bulls throughout the world, but the fertility of cows has decreased since the 1950s, more so when artificial insemination with cryopreserved semen has been used. In order to address this problem,...

BSP3 is a 15 kDa heparin- and phospholipid-binding protein that is secreted by bovine seminal vesicles and adsorbed onto sperm when they come in contact with vesicular secretions. There is evidence that BSP3, as well as two other BSP proteins, enhances sperm binding to oviductal epithelium. This binding holds sperm in a storage reservoir in the low...

Three Binder of SPerm proteins (BSP1, BSP3, BSP5) are secreted by bovine seminal vesicles into seminal plasma and adsorbed onto sperm. When sperm inseminated into the female reach the oviduct, the BSP proteins bind them to its epithelial lining, forming a sperm storage reservoir. Previously, we reported that binding of capacitated sperm to oviducta...

In order to better understand how sperm movement is regulated in the oviduct, we mated wild-type female mice with Acr-EGFP males that produce sperm with fluorescent acrosomes. The fluorescence improved our ability to detect sperm within the oviduct. Oviducts were removed shortly before or after ovulation and placed in chambers on a warm microscope...

Infertility is a significant health problem. On the other hand, unintended pregnancies also remain a major concern for women worldwide. Improved methods could be developed for diagnosing and treating infertility, as well as for contraception, if more were known about how sperm move through the female reproductive tract. Such information would also...

Hyperactivation, a swimming pattern of mammalian sperm in the oviduct, is essential for fertilization. It is characterized by highly asymmetrical flagellar beating, which is triggered by a rise in flagellar cytoplasmic Ca²⁺. In vivo, hyperactivation may be modulated to direct sperm toward oocytes. In our previous work, by using mouse sperm which ha...

Binder of SPerm (BSP) proteins are major heparin- and phospholipid-binding proteins secreted by bovine seminal vesicles and adsorbed onto epididymal sperm when they come in contact with vesicular secretions during ejaculation. There are three major BSPs in bovine seminal plasma: BSP1, BSP3, and BSP5. Each BSP alone enhances sperm binding to the ovi...

Hyperactivation in mammalian sperm is characterized by highly asymmetrical waveforms and an increase in the amplitude of flagellar bends. It is important for the sperm to be able to achieve hyperactivated motility in order to reach and fertilize the egg. Calcium (Ca(2+)) dynamics are known to play a large role in the initiation and maintenance of h...

Mammalian sperm must hyperactivate in order to fertilize oocytes. Hyperactivation is characterized by highly asymmetrical flagellar bending. It serves to move sperm out of the oviductal reservoir and to penetrate viscoelastic fluids, such as the cumulus matrix. It is absolutely required for sperm penetration of the oocyte zona pellucida. In order f...

Hyperactivation, a swimming pattern of mammalian sperm in the oviduct, is essential for fertilization. It is characterized by asymmetrical flagellar beating and an increase of cytoplasmic Ca(2+). We observed that some mouse sperm swimming in the oviduct produce high-amplitude pro-hook bends (bends in the direction of the hook on the head), whereas...

Interactions between bone and the reproductive system have until now been thought to be limited to the regulation of bone remodeling by the gonads. We now show that, in males, bone acts as a regulator of fertility. Using coculture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, though they fail to i...

In order to provide better diagnosis and treatment of infertility and to develop better contraceptive methods, more needs to be learned about how sperm move through the female reproductive tract. Crucial phases of mammalian sperm transport include passage through the cervix and uterotubal junction, storage in the oviductal sperm storage reservoir,...

Three regions of the ruminant oviduct play different roles in the progress of sperm: the uterotubal junction, isthmus, and ampulla. The uterotubal junction acts as a point of selection of sperm, requiring that sperm are progressively motile and express specific proteins in order to enter the oviduct. The isthmus stores sperm, preserving motility an...

In order to provide better diagnosis and treatment of infertility and to develop better contraceptive methods, more needs to be learned about how sperm move through the female reproductive tract. Crucial phases of mammalian sperm transport include passage through the cervix and uterotubal junction, storage in the oviductal sperm storage reservoir,...

Calcium (Ca2+) dynamics in mammalian sperm are directly linked to motility. These dynamics depend on diffusion, nonlinear fluxes, Ca2+ channels specific to the sperm flagellum, and other signaling molecules. The goal of this work is to couple Ca2+ dynamics to a mechanical model of a motile sperm within a viscous, incompressible fluid. An immersed b...

When bull sperm enter the oviduct, most bind to the epithelium in the lower oviduct to form a sperm reservoir. Sperm become capacitated before they leave the reservoir. It was reported that Bovine Seminal Plasma proteins (BSPs) enhance binding of bull sperm to the oviductal epithelium. BSPs are heparin- and phospholipid-binding proteins secreted by...

In mammals the number of sperm introduced into the female tract is orders of magnitude greater than the number of eggs available for fertilization. By the time spermatozoa reach the site of fertilization the ratio of sperm to egg has fallen due to regulation of sperm transport by the female tract. Male mice homozygous for a targeted mutation in pkd...

Hyperactivation, a motility pattern of mammalian sperm in the oviduct, is essential to fertilization. Hyperactivation helps sperm to swim effectively through oviductal mucus, to escape from the sperm reservoir, and to penetrate the cumulus matrix and zona pellucida of the oocyte. There is some evidence that mammalian sperm can undergo chemotaxis; h...

CatSpers are calcium (Ca(2+)) channels that are located along the principal piece of mammalian sperm flagella and are directly linked to sperm motility and hyperactivation. It has been observed that Ca(2+) entry through CatSper channels triggers a tail to head Ca(2+) propagation in mouse sperm, as well as a sustained increase of Ca(2+) in the head....

The mechanisms of sexual reproduction are expected to be complex and evolutionarily dynamic in internally fertilizing species, where numerous biochemical, physiological, morphological, and behavioral mechanisms mediate insemination, sperm migration, sperm storage, the maintenance of sperm viability, and sperm modification, all of which must be prop...

Female mammals exert control over when sperm can enter and ascend the oviduct. In most species, the entrance to the uterotubal junction presents a maze of mucosal folds to sperm and, in mice, the junction is known to close within an hour of mating. Once sperm enter into the oviduct, most are trapped and held in a storage reservoir. In many mammals,...

Capacitation is a complex and not well-understood process that encompasses all the molecular changes sperm must undergo to successfully fertilize an oocyte. In vitro fertilization has remained elusive in the horse, as evidenced by low in vitro fertilization (IVF) rates (0%-33%); moreover, only two foals have ever been produced using IVF. Incubation...

Sperm hyperactivation is characterised by high-amplitude, asymmetrical flagellar bending and is required to penetrate the oocyte zona pellucida. It was proposed that hyperactivation also enables spermatozoa to reach the oocyte by assisting escape from the oviductal sperm reservoir. To test this hypothesis, the behaviour of CatSper-null mouse sperma...

Sperm hyperactivation is critical to fertilization, because it is required for penetration of the zona pellucida. Hyperactivation may also facilitate release of sperm from the oviductal storage reservoir and may propel sperm through mucus in the oviductal lumen and the matrix of the cumulus oophorus. Hyperactivation is characterized by high amplitu...

Capacitation is a complex and still not well understood process that encompasses the molecular changes sperm must undergo to fertilize an oocyte. In several mammalian species capacitation can be mimicked in vitro, and has been correlated with increases in protein tyrosine phosphorylation, acrosomal exocytosis, hyperactivated motility, and fertiliza...

Soluble adenylyl cyclase (SACY) is an essential component of cAMP-signalling cascades that activate sperm motility and capacitate sperm. SACY activity is stimulated by HCO3– and Ca²⁺. Sperm from Sacy–/– (null) mice were immotile or weakly motile, but cAMP analogues N⁶,2′-O-dibutyryladenosine 3′,5′-cyclic monophosphate (dbcAMP) and adenosine 3′,5′-c...

The oviduct plays a vital role in ensuring successful fertilization and normal early embryonic development. The male inseminates many thousands or even millions of sperm, but this alone does not ensure that fertilization will be successful. The female tract, particularly the oviduct, provides filters that select for normal vigorously motile sperm....

The sperm of eutherian mammals are held in a storage reservoir in the caudal segment of the oviduct by binding to the mucosal epithelium. The reservoir serves to maintain the fertility of sperm during storage and to reduce the incidence of polyspermic fertilization. Bovine sperm bind to the epithelium via seminal vesicle secretory proteins in the b...

Poor sperm quality is the major cause of infertility in humans. Other than sex-linked factors, the genetic basis for male infertility is poorly defined, largely due to practical difficulties in studying the inheritance of this trait in humans. As an alternative, we have conducted forward genetic screens in mice to generate relevant models. We repor...

Mammalian sperm are held in a storage reservoir in the caudal segment of the oviduct by binding to the mucosal epithelium. In the bovine, we determined that seminal vesicle secretory proteins in the BSP family, namely PDC-109 (BSP A1/A2), BSP-A3, and BSP-30-kDa, coat the sperm head and enable sperm to bind to the epithelium. Our next objective was...

Sperm hyperactivated motility is characterized by high flagellar bend amplitude and asymmetrical beating, which are detected by computer-assisted sperm motility analysis as increased curvilinear velocity and lateral head movement. It is required for sperm penetration of the oocyte zona pellucida during fertilization and is induced by an increase in...

In order to fertilize, mammalian sperm must hyperactivate. Hyperactivation is triggered by increased flagellar Ca(2+), which switches flagellar beating from a symmetrical to an asymmetrical pattern by increasing bending to one side. Thimerosal, which releases Ca(2+) from internal stores, induced hyperactivation in mouse sperm within seconds, even w...

In mammalian sperm, the flagellar midpiece and principal piece contain different signalling molecules and ion channels. For example, the soluble adenylyl cyclase (sAC), which is required for activation of motility, is restricted to the midpiece, while the plasma membrane calcium channels CatSper1 and CatSper2, which are required for hyperactivation...

Artificial insemination with sexed semen, in vitro fertilisation and intracytoplasmic sperm injection have been used to reproduce animals, but often not as successfully as natural mating. Learning more about how spermatozoa normally interact with the female tract can provide inspiration for developing improvements in assisted reproduction. The pres...

This chapter focuses on the sperm transport through the cervix. In some vaginal semen depositors, such as primates and dairy cattle, sperm presumably pass through the cervix by swimming through the cervical mucus. After deposition in the cranial vagina, sperm of humans and dairy cows enter the cervical canal rapidly, where they encounter large volu...

Fertility of spermatozoa depends on maintenance of the mitochondrial transmembrane potential (Deltapsi(m)), which is generated by the electron-transport chain and regulated by an oxidation-reduction equilibrium of reactive oxygen intermediates, pyridine nucleotides, and glutathione (GSH). Here, we report that male mice lacking transaldolase (TAL)(-...

On ejaculation, sperm become coated with proteins secreted by the male accessory sex glands. In the bull, these proteins consist predominantly of the bovine seminal plasma family of proteins (BSPs): PDC-109 (BSP-A1/-A2), BSP-A3, and BSP-30-kDa. PDC-109 plays a role in forming an oviductal sperm reservoir by enabling sperm to bind to oviductal epith...

At coitus, human sperm are deposited into the anterior vagina, where, to avoid vaginal acid and immune responses, they quickly contact cervical mucus and enter the cervix. Cervical mucus filters out sperm with poor morphology and motility and as such only a minority of ejaculated sperm actually enter the cervix. In the uterus, muscular contractions...

Hyperactivated motility is observed among sperm in the mammalian oviduct near the time of ovulation. It is characterized by high-amplitude, asymmetrical flagellar beating and assists sperm in penetrating the cumulus oophorus and zona pellucida. Elevated intracellular Ca2+ is required for the initiation of hyperactivated motility, suggesting that ca...

Mammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they "capacitate," i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm...

Loss of calmegin, a testis-specific putative chaperone protein of the endoplasmic reticulum, leads to male sterility because the sperm show defects in migration into the oviduct and do not bind to the zona pellucida. To clarify the mechanism of defective migration, XY <--> XY chimeras were produced by aggregating wild-type embryos with embryos of t...

Hyperactivated sperm motility is characterized by high-amplitude and asymmetrical flagellar beating that assists sperm in penetrating the oocyte zona pellucida. Other functional changes in sperm, such as activation of motility and capacitation, involve cross talk between the cAMP/PKA and tyrosine kinase/phosphatase signaling pathways. Our objective...

Sperm reservoirs have been found in the oviducts of several species of mammals. In cattle, the reservoir is formed by the binding of sperm to fucose-containing glycoconjugates on the surface of oviductal epithelial cells. A fucose-binding molecule was purified from sperm extracts and identified as PDC-109 (BSP-A1/A2), a protein that is secreted by...

Mammalian sperm commonly show hyperactivated motility just before fertilization. The movement of hyperactivated sperm appears different in fluids of different viscosity and elasticity and in different species, but basically it involves an increase in flagellar bend amplitude and, usually, beat asymmetry. Hyperactivation may be critical to the succe...

Hyperactivated sperm motility is usually characterized by high-amplitude flagellar bends and asymmetrical flagellar beating. There is evidence that an inositol 1,4,5-trisphosphate (IP3) receptor-gated Ca2+ store in the base of the flagellum provides Ca2+ to initiate hyperactivation; however, the identity of the store was not known. Ca2+ stores are...

Contents Hyperactivation is a movement pattern seen in sperm at the site and time of fertilization in mammals. It may be critical to the success of fertilization, because it enhances the ability of sperm to detach from the wall of the oviduct, to move around in the labyrinthine lumen of the oviduct, to penetrate mucous substances and, finally, to p...

Millions of spermatozoa are inseminated into the mammalian female genital tract in order to fertilize only one or a few oocytes. The movement of spermatozoa through the female genital tract is actually regulated by the female so that a few reach the oocyte in the oviduct (fallopian tube) and only one of them succeeds in fertilizing it. This is acco...