Biology subjects

Kervarrec, C.

Publications and source records attributed to Kervarrec, C..

3 recordsLinked to original sources

bioRxiv2025

Paternal ancestral gestational exposure to neonicotinoid thiacloprid induces transgenerational alteration in DNA methylation germline germline-specific genes in female ovaries.

BackgroundNeonicotinoids, a widely used class of insecticides, have raised concerns due to their potential role in the decline of bee populations. Accumulating pieces of evidence suggest that these chemicals may also pose risks to human and animal health. ObjectivesThis study investigates the transgenerational effects of thiacloprid (Thia), a neonicotinoid, on the female reproductive system. MethodsPregnant outbred Swiss female mice were exposed to 0 and 6 mg/kg/day of thiacloprid from embryonic days E6.5 to E15.5. Adult female F1 and F3 progeny ovaries were examined for morphological abnormalities by using hematoxylin and eosin (H&E) staining of paraffin sections. Additionally, estradiol levels were assessed by ELISA using blood serum. A marker of mitosis, phosphorylated histone H3 at serine 10 (PhosphoHisH3ser10) levels, was analyzed by immunofluorescence, DNA methylation at some regions was analyzed by MeDIP, and RT-qPCR assessed gene expression. ResultsThe gestational exposure to thiacloprid led to an increased formation of multi-oocyte follicles in directly exposed F1 generation ovaries but not in F3. We observed a reduction in serum estradiol levels in both F1 and F3 females. In direct F1 exposed progeny, we determined an increase in (PhosphoHisH3ser10) in granulosa cells. Additionally, alterations in DNA methylation were observed in germline reprogramming-responsive genes in embryonic ovaries, as well as the DNA methylation was altered at these genes in both the F1 and F3 ovaries. The modified DNA methylation was associated with changes in gene expression in adult ovaries of the F1 and F3 generations in genes encoding transcription and hormonal signaling factors. ConclusionOur findings demonstrate that ancestral gestational exposure to thiacloprid induces transgenerational effects on female reproductive health, potentially through epigenetic modifications of paternal germ cells.

cell biology↗

bioRxiv2025

Transgenerational effects induced by thiacloprid in Anterior prostate tissue are associated with alterations in DNA methylation at developmental genes.

BackgroundNeonicotinoids are widely used pesticides that cause a catastrophic decrease in bee and bumblebee populations worldwide. In addition to insects, neonicotinoids have toxic effects on other species, including lizards, birds, and mammals. Previous studies have shown that gestational exposure to thiacloprid has transgenerational effects on the testis and thyroids. ObjectivesIn this project, we described the epigenetic effects of thiacloprid on anterior prostate tissue in directly exposed F1 males and nondirectly exposed F3 males MethodsWe used paraffin sections for morphological analysis, frozen tissue sections for immunofluorescence analysis, RT-qPCR for gene expression analysis, histone purification and western blotting for protein analysis, and ChIP-qPCR for histone H3K4me3 occupancy analysis. The resultsWe observed a tendency toward an increase in epithelial hyperplasia in F1 and not a significant increase in F3. We detected elevated levels of phosphorylated histone H3 at serine 10, a marker of mitosis, in both the F1 and F3 prostates. A significant increase in the level of the Ki-67 marker of proliferation was detected in the F1 anterior prostate but not in the F3 anterior prostate. Hox gene expression was upregulated in F1 anterior prostate and downregulated in F3 anterior prostate. The changes in gene expression were associated with histone H3K4me3 alterations at the promoters of the genes. We determined that regions of Hox genes that play important roles in the anterior prostate have altered DNA methylation in the sperm of F1 and F3. These alterations in DNA methylation were negatively related to gene expression. ConclusionOur analysis revealed that gestational exposure to thiacloprid caused epigenetic alterations in the anterior prostates of F1 males and nondirectly exposed F3 males. DNA methylation changes at the promoters of anterior prostate development genes could be responsible for transgenerational effects in anterior prostates.

developmental biology↗

bioRxiv2021

Interactome analyses reveal profound proteasome structural and functional rearrangements throughout mammalian spermatogenesis

During spermatogenesis, spermatogonia undergo a series of mitotic and meiotic divisions on their path to spermatozoa. To achieve this, a succession of processes requiring high proteolytic activity are in part orchestrated by the proteasome. The spermatoproteasome (s20S) is specific to the developing gametes, in which the gamete-specific 4s subunit replaces the 4 isoform found in the constitutive proteasome (c20S). Although the s20S is conserved across species and was shown to be crucial for germ cell development, its mechanism, function and structure remain incompletely characterized. Here, we used advanced mass spectrometry (MS) methods to map the composition of proteasome complexes and their interactomes throughout spermatogenesis. We observed that the s20S becomes highly activated as germ cells enter meiosis, mainly through a particularly extensive 19S activation and, to a lesser extent, PA200 binding. Additionally, the proteasome population shifts from c20S (98%) to s20S (>82-92%) during differentiation, presumably due to the shift from 4 to 4s expression. We demonstrated that s20S, but not c20S, interacts with components of the meiotic synaptonemal complex, where it may localize via association with the PI31 adaptor protein. In vitro, s20S preferentially binds to 19S, and displays higher trypsin- and chymotrypsin-like activities, both with and without PA200 activation. Moreover, using MS methods to monitor protein dynamics, we identified significant differences in domain flexibility between 4 and 4s. We propose that these differences induced by 4s incorporation result in significant changes in the way the s20S interacts with its partners, and dictate its role in germ cell differentiation.

biochemistry↗