Influence of the Temperature and the Genotype of the HSP90AA1 Gene over Sperm Chromatin Stability in Manchega Rams

The present study addresses the effect of heat stress on males' reproduction ability. For that, we have evaluated the sperm DNA fragmentation (DFI) by SCSA of ejaculates incubated at 37°C during 0, 24 and 48 hours after its collection, as a way to mimic the temperature circumstances to which spermatozoa will be subject to in the ewe uterus. The effects of temperature and temperature-humidity index (THI) from day 60 prior collection to the date of semen collection on DFI were examined. To better understand the causes determining the sensitivity of spermatozoa to heat, this study was conducted in 60 males with alternative genotypes for the SNP G/C−660 of the HSP90AA1 promoter, which encode for the Hsp90α protein. The Hsp90α protein predominates in the brain and testis, and its role in spermatogenesis has been described in several species. Ridge regression analyses showed that days 29 to 35 and 7 to 14 before sperm collection (bsc) were the most critical regarding the effect of heat stress over DFI values. Mixed model analyses revealed that DFI increases over a threshold of 30°C for maximum temperature and 22 for THI at days 29 to 35 and 7 to 14 bsc only in animals carrying the GG−660 genotype. The period 29–35 bsc coincide with the meiosis I process for which the effect of the Hsp90α has been described in mice. The period 7–14 bsc may correspond with later stages of the meiosis II and early stages of epididymal maturation in which the replacement of histones by protamines occurs. Because of GG−660 genotype has been associated to lower levels of HSP90AA1 expression, suboptimal amounts of HSP90AA1 mRNA in GG−660 animals under heat stress conditions make spermatozoa DNA more susceptible to be fragmented. Thus, selecting against the GG−660 genotype could decrease the DNA fragmentation and spermatozoa thermal susceptibility in the heat season, and its putative subsequent fertility gainsPublishe

Effets transgénérationnels des chimiothérapies : l’exposition du père influence-t-elle la santé des générations futures ?

International audienceThe number of cancer survivors is increasing and their quality of life is becoming a major public health issue. Cancer treatments reduce men's reproductive health by targeting spermatogenesis. Ultimately, DNA, chromatin and the epigenome of spermatozoa can be altered in cancer survivors. Knowing whether the history of cancer and the treatments received can have consequences on the health of their offspring is therefore a fundamental question for these patients. This review gathers the experimental and epidemiological evidences of the effects observed on the direct descendants and on several generations, and draws up the state of knowledge on the mechanisms potentially involved. Experimental data describe inter- and transgenerational effects of paternal exposure depending on the type of treatment, dose and time of exposure. In the human population, the analysis of the effects specifically due to chemotherapy is still limited because they are often combined with irradiation treatments. However, it appears that chemotherapy agents affect the birth rate but do not have a significant impact on the health of the children born. Nevertheless, the demonstration of modifications of the sperm epigenome in cancer survivors, even after a period of remission, as well as changes in the sperm of the progeny in animal models, suggests a possible transgenerational transmission that remains to be studied in the human population.Le nombre de survivants de cancer augmente et leur qualité de vie devient un enjeu majeur de santé publique. Les traitements de cancer diminuent la fonction de reproduction des hommes en ciblant la spermatogenèse. En fin de compte, l’ADN, la chromatine et l’épigénome des spermatozoïdes peuvent être altérés chez les survivants de cancer. Savoir si l’historique de cancer et les traitements reçus peuvent avoir des conséquences sur la santé de leur descendance est donc une question fondamentale pour ces patients. Cette revue de la littérature regroupe les évidences expérimentales et épidémiologiques des effets observés sur les descendants directs et sur plusieurs générations, et dresse l’état des connaissances sur les mécanismes potentiellement impliqués. Les données expérimentales décrivent des effets inter- et transgénérationnels d’une exposition paternelle en fonction du type de traitement, de la dose et du temps d’exposition. Dans la population humaine, l’analyse des effets spécifiquement dus aux chimiothérapies est encore limitée, car elles sont souvent combinées à des traitements d’irradiations. Toutefois, il apparaît que les agents de chimiothérapies affectent le taux de natalité, mais n’ont pas de conséquences significatives sur la santé des enfants nés. Cependant, la démonstration de modifications de l’épigénome des spermatozoïdes des survivants de cancer même après une période de rémission ainsi que chez les descendants dans des modèles animaux suggèrent une possible transmission transgénérationnelle qui reste à étudier dans la population humaine

Identification of reaction networks for bioprocesses: determination of a partially unknown pseudo-stoichiometric matrix

In this paper we propose a methodology to determine the structure of the pseudo-stoichiometric coefficient matrix K in a mass balance-based model and to identify its coefficients from a set of available data. The first stage consists in estimating the number of reactions that must be taken into account to represent the main mass transfer within the bioreactor. This provides the dimension of K. Then we propose a method to directly determine the structure of the matrix (i.e. mainly its zeros and the signs of its coefficients). These methods are illustrated with simulations of a process of lipase production from olive oil by Candida rugosa

Prebiotics Supplementation Impact on the Reinforcing and Motivational Aspect of Feeding.

Energy homeostasis is tightly regulated by the central nervous system which responds to nervous and circulating inputs to adapt food intake and energy expenditure. However, the rewarding and motivational aspect of food is tightly dependent of dopamine (DA) release in mesocorticolimbic (MCL) system and could be operant in uncontrolled caloric intake and obesity. Accumulating evidence indicate that manipulating the microbiota-gut-brain axis through prebiotic supplementation can have beneficial impact of the host appetite and body weight. However, the consequences of manipulating the implication of the microbiota-gut-brain axis in the control motivational and hedonic/reinforcing aspects of food are still underexplored. In this study, we investigate whether and how dietary prebiotic fructo-oligosaccharides (FOS) could oppose, or revert, the change in hedonic and homeostatic control of feeding occurring after a 2-months exposure to high-fat high-sugar (HFHS) diet. The reinforcing and motivational components of food reward were assessed using a two-food choice paradigm and a food operant behavioral test in mice exposed to FOS either during or after HFHS exposure. We also performed mRNA expression analysis for key genes involved in limbic and hypothalamic control of feeding. We show in a preventive-like approach, FOS addition of HFHS diet had beneficial impact of hypothalamic neuropeptides, and decreased the operant performance for food but only after an overnight fast while it did not prevent the imbalance in mesolimbic markers for DA signaling induced by palatable diet exposure nor the spontaneous tropism for palatable food when given the choice. However, when FOS was added to control diet after chronic HFHS exposure, although it did not significantly alter body weight loss, it greatly decreased palatable food tropism and consumption and was associated with normalization of MCL markers for DA signaling. We conclude that the nature of the diet (regular chow or HFHS) as well as the timing at which prebiotic supplementation is introduced (preventive or curative) greatly influence the efficacy of the gut-microbiota-brain axis. This crosstalk selectively alters the hedonic or motivational drive to eat and triggers molecular changes in neural substrates involved in the homeostatic and non-homeostatic control of body weight