Summary Olfactory signals influence social interactions in a variety of species [1, 2]. In mammals, pheromones and other social cues can promote mating or aggression behaviors, can communicate information about social hierarchies, genetic identity and health status, and can contribute to associative learning [1–5]. However, the molecular, cellular and neural mechanisms underlying many olfactory-mediated social interactions remain poorly understood. Here, we report that a specialized olfactory subsystem that includes olfactory sensory neurons (OSNs) expressing the receptor guanylyl cyclase GC-D, the cyclic nucleotide-gated channel subunit CNGA3 and the carbonic anhydrase isoform CAII (GC-D+ OSNs) [6–11] is required for the acquisition of socially transmitted food preferences (STFPs) in mice. Using electrophysiological recordings from gene-targeted mice, we show that GC-D+ OSNs are highly sensitive to the volatile semiochemical carbon disulfide (CS2), a component of rodent breath and a known social signal mediating the acquisition of STFPs [12–14]. Responses to sub-micromolar concentrations of CS2 in the main olfactory epithelium or in identified GC-D+ OSNs are absent in mice lacking CNGA3 or CAII and drastically reduced in mice lacking GC-D. Mice in which GC-D+ OSN transduction mechanisms have been disrupted fail to acquire STFPs from either live or surrogate demonstrator mice and do not exhibit neuronal activation of the ventral subiculum of the hippocampus, a brain region implicated in STFP retrieval [15]. Our findings indicate that GC-D+ OSNs detect chemosignals that facilitate food-related social interactions.

Background: Frequency and asymmetry of the flagellar waveform of sperm are controlled by cAMP-mediated and Ca 2+ -dependent signaling pathways, but additional mechanisms modulate sperm swimming behavior. Here, high-speed imaging of free-swimming mouse sperm simultaneously reports flagellar waveform, orientation of sperm head, and swimming paths. Results: We found many sperm roll (rotate around their long axis) at intervals closely tied to flagellar beat frequency, allowing an asymmetrical flagellar beat to form linear averaged swimming trajectories. For non-rolling sperm, flagellar waveform asymmetry dictated circular path trajectories. Sparse rolling produced abrupt changes in swimming trajectories that occurred spontaneously, unaffected by blockade or engagement of cAMP-or Ca 2+ -mediated flagellar responses. Still other sperm loosely attached (tethered) to surfaces or other cells. Sperm tethered to each other in duos or trios could have narrowed swimming paths, allowing enhanced progression. Conclusions: We propose that transient episodes of rolling and reversible attachments are organizing principles that determine diverse swimming behaviors, which may have roles in selection of the fertilizing sperm.

Extracellular vesicles (EVs) are released from almost all cells and tissues. They are able to transport substances (e.g. proteins, RNA or DNA) at higher concentrations than in their environment and may adhere in a receptor-controlled manner to specific cells or tissues in order to release their content into the respective target structure. Blood contains high concentrations of EVs mainly derived from platelets, and, at a smaller amount, from erythrocytes. The female and male reproductive tracts produce EVs which may be associated with fertility or infertility and are released into body fluids and mucosas of the urogenital organs. In this review, the currently relevant detection methods are presented and critically compared. During pregnancy, placenta-derived EVs are dynamically detectable in peripheral blood with changing profiles depending upon progress of pregnancy and different pregnancy-associated pathologies, such as preeclampsia. EVs offer novel non-invasive diagnostic tools which may reflect the situation of the placenta and the foetus. EVs in urine have the potential of reflecting urogenital diseases including cancers of the neighbouring organs. Several methods for detection, quantification and phenotyping of EVs have been established, which include electron microscopy, flow cytometry, ELISA-like methods, Western blotting and analyses based on Brownian motion. This review article summarises the current knowledge about EVs in blood and cord blood, in the different compartments of the male and female reproductive tracts, in trophoblast cells from normal and pre-eclamptic pregnancies, in placenta ex vivo perfusate, in the amniotic fluid, and in breast milk, as well as their potential effects on natural killer cells as possible targets.

HCO3 − is the signal for early activation of sperm motility. In vivo, this occurs when sperm come into contact with the HCO3 − containing fluids in the reproductive tract. The activated motility enables sperm to travel the long distance to the ovum. In spermatozoa HCO3 − stimulates the atypical sperm adenylyl cyclase (sAC) to promote the cAMP-mediated pathway that increases flagellar beat frequency. Stimulation of sAC may occur when HCO3 − enters spermatozoa either directly by anion transport or indirectly via diffusion of CO2 with subsequent hydration by intracellular carbonic anhydrase (CA). We here show that murine sperm possess extracellular CA IV that is transferred to the sperm surface as the sperm pass through the epididymis. Comparison of CA IV expression by qRT PCR analysis confirms that the transfer takes place in the corpus epididymidis. We demonstrate murine and human sperm respond to CO2 with an increase in beat frequency, an effect that can be inhibited by ethoxyzolamide. Comparing CA activity in sperm from wild-type and CA IV−/− mice we found a 32.13% reduction in total CA activity in the latter. The CA IV−/− sperm also have a reduced response to CO2. While the beat frequency of wild-type sperm increases from 2.86±0.12 Hz to 6.87±0.34 Hz after CO2 application, beat frequency of CA IV−/− sperm only increases from 3.06±0.20 Hz to 5.29±0.47 Hz. We show, for the first time, a physiological role of CA IV that supplies sperm with HCO3 −, which is necessary for stimulation of sAC and hence early activation of spermatozoa.

Lactate is provided to spermatogenic cells by Sertoli cells as an energy substrate and its transport is regulated by H(+)-monocarboxylate co-transporters (MCTs). In the case of several cell types it is known that MCT1 is associated with basigin and MCT2 with embigin. Here we demonstrate co-localization and co-immunoprecipitation of basigin with both MCT1 and MCT2 in sperm, whereas no interaction with embigin was detectable. An investigation of the functional activity of MCT proteins revealed that it was mainly the application of L-lactate which resulted in a decrease in pH(i) . The pH(i) changes were blocked with α-cyano-4-OH cinnamate and the preference for L-lactate-as opposed to D-Lactate-was demonstrated by the determination of ATP after exposure to both lactate isomers. We propose that basigin interacts with MCT1 and MCT2 to locate them properly in the membrane of spermatogenic cells and that this may enable sperm to utilize lactate as an energy substrate contributing to cell survival.