Biology subjects

Balbach, M.

Publications and source records attributed to Balbach, M..

5 recordsLinked to original sources

bioRxiv2026

Daylight, Daily Rhythms, and Downstream Physiology: A Translational Study in Diurnal Nile Grass Rats (Arvicanthis niloticus)

The circadian system evolved under natural light-dark cycles, while modern humans spend much of their time indoors under electric lighting that differs substantially from daylight in intensity, spectral composition, and temporal structure. How such lighting environments influence circadian system has not been systematically examined in a diurnal animal model under ecologically relevant conditions. In this study, we used the diurnal Nile grass rat (Arvicanthis niloticus) to assess daily locomotor rhythms across four lighting conditions designed to approximate common human exposure scenarios: rectangular daylight (D65-R; [~]5,600 lux), semi-sigmoidal daylight mimicking natural intensity dynamics (D65-S; matched peak intensity with [~]50% lower cumulative energy), fluorescent indoor light (F12; [~]150 lux), and fluorescent light supplemented with a one-hour midday daylight pulse (F12+D65-P). Using a within-subject design (n = 8), male grass rats were housed under each condition for two weeks. D65-R produced the highest daytime activity levels and the strongest day/night activity ratio, consistent with robust circadian entrainment. Despite matching peak intensity, D65-S did not yield comparable circadian outcomes, indicating that cumulative photon exposure, rather than peak intensity alone, contributes to entrainment strength. Notably, the addition of a one-hour midday daylight pulse (D65-P) partially increased circadian amplitude under otherwise fluorescent conditions, with higher periodogram amplitude relative to F12 alone. A separate cohort of males was exposed to D65-R or F12 for six weeks (n = 10/condition) to assess physiological outcomes, including metabolic and reproductive measures. Compared with the D65-R group, F12 group showed higher diabetic rate (10% vs. 40%) and reduced sperm mobility (45{+/-}6 vs. 19{+/-}1 %), consistent with potential downstream correlates of circadian rhythm disruption. Together, these findings demonstrate that lighting conditions characteristic of indoor environments produce weaker circadian organization than daylight-equivalent lighting in a diurnal rodent, which underscore the importance of light quality in shaping circadian rhythms and downstream physiological processes.

animal behavior and cognition↗

bioRxiv2025

Sperm meet the elevated energy demands to attain fertilization competence by increasing flux through aldolase

Prior to ejaculation, sperm are stored in the epididymis in a resting metabolic state. Upon ejaculation, sperm must alter their metabolism to generate the energy needed to support the motility and maturation process known as capacitation to reach and fertilize the oocyte. How sperm regulate the capacitation-induced increase in carbon flux is unknown. Here, we use 13C stable isotope labeling to follow glucose metabolism through sperm central carbon metabolic network before and after sperm activation. We identify regulatory steps which sperm use to alter their metabolic state from resting to highly active. In activated sperm, glucose flux through glycolysis is increased at the expense of the pentose phosphate pathway to increase energy yield. Increased glycolytic activity seems to be due to capacitation-induced stimulation of flux through aldolase. In the mitochondria-containing midpiece, glycolytically generated pyruvate feeds the TCA cycle to further maximize energy yield via oxidative phosphorylation. In the mitochondria-free principal piece of the tail, pyruvate produced from glycolysis is reduced to lactate by lactate dehydrogenase. Reduction to lactate regenerates oxidized NAD+ ensuring a sufficient supply to support glycolysis. The resultant lactate is at least partially secreted. Finally, we find evidence that there is an as yet unknown endogenous source of energy in sperm feeding the upregulation of TCA cycle intermediates. These studies provide the most complete picture of the metabolic shift which occurs in capacitating sperm. Significance statementA rapid switch from a quiescent to a high energy-demanding state during ejaculation is essential for sperm to reach and fertilize the oocyte. Somatic cells also undergo bioenergetic switches from low to very high energy demand. However, because metabolic processes essential for proliferation are going on in parallel, it is difficult to identify the molecular mechanisms regulating the increase in ATP production. This study represents the first complete picture of the metabolic reprogramming that happens in sperm upon ejaculation. Using stable isotope labeling, we identify rate-limiting enzymatic steps and points of regulation directing the changes in metabolic flux. Our sperm metabolic studies allow us to identify conserved mechanisms of metabolic regulation that are crucial for the survival of mammalian cells.

biochemistry↗

bioRxiv2024

Deciphering rapid cell signaling and control of cell motility by reverse opto-chemical engineering

Cells transform complex environmental stimuli into physiological responses. For time-varying stimuli or motile cells, the perception of the environment depends on the temporal stimulus pattern and cell motion, respectively. Here we report a concept, "reverse optochemical engineering" (ROCE), that uses temporal light patterns and photo-triggers to expose cells to virtual sensory landscapes while recording in real time their physiological responses and motor behavior. We studied cyclic-nucleotide signaling in cell lines, sperm, olfactory neurons, and cardiomyocytes. The technique can be employed for remote control of motility by light. We reprogrammed sperm from a chemotactic to a phototactic cell that is attracted towards light. The method provides new opportunities to decipher the mechanisms and signaling molecules underlying rapid cellular computations, and thus reveal the wire diagram of cellular networks.

biophysics↗

bioRxiv2021

Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization

Soluble adenylyl cyclase (sAC: ADCY10) is essential for activating dormant sperm. Studies of freshly dissected mouse sperm identified sAC as needed for initiating capacitation and activating motility. We now use an improved sAC inhibitor, TDI-10229, for a comprehensive analysis of sAC function in human sperm. Unlike dissected mouse sperm, human sperm are collected post-ejaculation, after sAC activity has already been stimulated. Even in ejaculated human sperm, TDI-10229 interrupts stimulated motility and capacitation, and it prevents acrosome reaction in capacitated sperm. At present, there are no non-hormonal, pharmacological methods for contraception. Because sAC activity is required post-ejaculation at multiple points during the sperms journey to fertilize the oocyte, sAC inhibitors define candidates for non-hormonal, on-demand contraceptives suitable for delivery via intravaginal devices in females.

pharmacology and toxicology↗

bioRxiv2021

A conserved role of Parkinson-associated DJ-1 metabolites in sperm motility, mitosis, and embryonic development

Fertility rates in the developing world have dramatically dropped in the last decades. This drop is likely due to a decline in sperm quality and women having children at older ages. Loss of function mutations in DJ-1, a Parkinsons associated gene, are linked to alterations in multiple cellular processes such as mitochondrial activity, ROS production or sperm motility and lead to an early onset of Parkinsons disease and male infertility in humans and other species. Glycolate (GA) and D-lactate (DL), products of DJ-1 glyoxalase activity, sustain mitochondrial function and protect against environmental aggressions. We, therefore, tested whether these substances could also have a rescue effect on these phenotypes. Here, we show that DJ-1 loss of function not only affects sperm motility but also leads to defects in mitosis and an age-dependent increase in the abortion rate. Remarkably, whereas DL was only able to rescue embryonic lethality in C. elegans, GA rescued these phenotypes in all model systems tested and even increased sperm motility in wild-type sperm. These positive effects seem to be mediated through an increase in NAD(P)H production and the regulation of intracellular calcium. These findings not only strongly suggest GA as a new therapeutic candidate to improve male and female fertility but also show its potential to treat diseases associated with a decline in mitochondrial function or to improve mitochondrial function in aging.

developmental biology↗