Biology subjects

Testa, E.

Publications and source records attributed to Testa, E..

3 recordsLinked to original sources

bioRxiv2024

Vertical sleeve gastrectomy in rodents: impact on metabolic, cardiovascular and hepatic functions of mothers and perinatal consequences

BackgroundMaternal obesity is a well-known risk factor for obstetrical complications during pregnancy, and cardiovascular and metabolic pathologies in the offspring. In the last two decades, bariatric surgery has emerged as the most effective treatment for severe obesity, and is known to improve fertility, leading to a rise in procedures among women of childbearing age. ObjectivesThis study investigates the impact of pre-conceptional sleeve gastrectomy (SG) on metabolic, cardiovascular and hepatic functions of mothers at short and middle terms after surgery, and its perinatal consequences. MethodsSprague-Dawley female control rats (CM) received a standard diet, while others were fed a high-fat, high-sugar diet (HFHS). HFHS rats were divided into obese mothers (OM) and sleeve gastrectomy mothers (SM). One month after surgery, all groups underwent gestation and subsequent lactation Metabolic function was assessed at 1 and 4 months after surgery; cardiovascular and hepatic functions were evaluated only 4 months after SG. ResultsFrom 1 month post-surgery, SM showed normalized leptin and insulin levels compared to OM. Moreover, SG normalized body weight associated with a decreased white adipose tissue weight and adipocyte size at 4 months post-surgery. Interestingly, although steatosis has been detected in HFHS rats, SM exhibited only hepatic fibrosis at 4 months post-surgery. Moreover, SM showed a hypertrophic remodeling of thoracic aorta without effect on its vasoreactivity but along with endothelial dysfunction of mesenteric artery, associated with a stronger involvement of COX/PGI2 pathway. In the offspring, obesity in mothers was associated to a decreased liter size, reversed by sleeve gastrectomy without any effect on the birth weight of pups. ConclusionWhile this study reports an improvement of metabolic function at short- and medium-terms after bariatric surgery, our results highlight an alteration of hepatic and vascular functions by sleeve gastrectomy, with minimal effect on the offspring in the perinatal period.

physiology↗

bioRxiv2018

ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between heterologous sex chromosomes in mice

Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a critical component of complexes of DSB-promoting proteins which assemble on meiotic chromosome axes. Genome-wide, ANKRD31 deficiency causes delayed recombination initiation. In addition, loss of ANKRD31 alters DSB distribution owing to reduced selectivity for sites that normally attract DSBs. Strikingly, ANKRD31 deficiency also abolishes uniquely high rates of recombination that normally characterize pseudoautosomal regions (PARs) of X and Y chromosomes. Consequently, sex chromosomes do not form crossovers leading to chromosome segregation failure in ANKRD31-deficient spermatocytes. These defects are accompanied by a genome-wide delay in assembling DSB-promoting proteins on axes and a loss of a specialized PAR-axis domain that is highly enriched for DSB-promoting proteins. Thus, we propose a model for spatiotemporal patterning of recombination by ANKRD31-dependent control of axis-associated complexes of DSB-promoting proteins.

cell biology↗

bioRxiv2017

H2AFX AND MDC1 PROTECT GENOMIC INTEGRITY IN MALE GERM CELLS BY PROMOTING RECOMBINATION AND ACTIVATION OF THE RECOMBINATION-DEPENDENT CHECKPOINT

In somatic cells, H2afx and Mdc1 are close functional partners in DNA repair and damage response. However, it is not known whether they are also involved in the maintenance of genome integrity in meiosis. By analyzing chromosome dynamics in H2afx-/- spermatocytes, we found that synapsis of the autosomes and X-Y chromosomes were impaired in a relevant fraction of cells. Such defect correlated with an abnormal recombination profile. Conversely, Mdc1 was dispensable for the synapsis of the autosomes, and only played a minor role in X-Y synapsis, relatively to H2afx. This suggested that those genes have non-overlapping functions in chromosome synapsis. However, we observed that both genes play a similar role in the assembly of MLH3 onto chromosomes, a key step in crossover formation. Moreover, we showed that H2afx and Mdc1 cooperate in promoting the activation of the recombination-dependent checkpoint, a mechanism that restrains the differentiation of cells with unrepaired DSBs. This occurs by a mechanism that involves P53. Overall, our data showed that, in male germ cells, H2afx and Mdc1 promote the maintenance of genome integrity.

developmental biology↗