Biology subjects

Molangiri, A.

Publications and source records attributed to Molangiri, A..

3 recordsLinked to original sources

bioRxiv2023

In-utero exposure to estrogen-mimicking bisphenols alters bone mineralization in the offspring

Exposure to plastic-derived estrogen-mimicking endocrine-disrupting bisphenols can have a long-lasting effect on bone health. However, gestational exposure to below tolerable daily intake (TDI) of bisphenol A (BPA) and its substitute, bisphenol S (BPS), on offsprings bone mineralization is unclear. This study examined the effects of in-utero bisphenol exposure on the growth and bone density of the offspring rats. Pregnant Wistar rats were exposed to BPA and BPS (0.0, 0.4 g/kg bw) via oral gavage from gestational day 4 to 21. The bone density, IGF-1, osteocalcin, and calcium levels were measured by DEXA, ELISA and AAS, respectively. The bisphenols action on canonical BMP signaling was examined in osteoblast SaOS-2 cells. Maternal exposure to bisphenols (BPA and BPS) increased the body weight, bone mineral content, and density in the offspring aged 30 and 90 days (p<0.05). Plasma IGF-1, calcium, osteocalcin, and alkaline phosphatase activities were altered in BPA-exposed offspring (p<0.05). The bisphenols exposure to SaOS-2 cells decreased its viability in a dose-dependent manner and promoted the cell cycle progression of the S/G2-M phase (p<0.05). The expression of BMP1, BMP4, and intracellular signalling mediators SMAD1, SMAD5, and RUNX2 mRNAs was altered upon bisphenol exposure in these cells (p<0.05). The bone mineralization index and expression of extracellular matrix proteins such as ALPL, COL1A1, DMP1, and FN1 were downregulated (p<0.05). Bisphenol co-incubation with noggin decreased TGF-{beta}1 expression, indicating its involvement in bone mineralization. Overall, exposure to bisphenols (BPA and BPS) during gestation altered growth and bone mineralization in the offspring by modulating canonical BMP/ TGF-{beta}1 signalling mediators. HighlightsO_LIGestational exposure to low doses of bisphenol increases whole-body BMC and BMD in the offspring. C_LIO_LIIn-utero BPA exposure increased plasma IGF-1 and gla-type osteocalcin, a marker of osteoblast activity in the offspring. C_LIO_LIBisphenol exposure modulates Smad-dependent BMP signaling in the SaOS-2 cells. C_LI

developmental biology↗

bioRxiv2023

Gestational exposure to bisphenol S induces microvesicular steatosis by promoting lipogenesis and inflammation in male rat offspring

Fetal exposure to endocrine-disrupting bisphenol A (BPA) showed a long-lasting programming effect on organ development and predisposed to the metabolic risk of adult diseases. However, limited data on developmental exposure to BPA-substitute bisphenol S (BPS) in predisposing liver metabolic disease is available. Here, the effects of BPS exposure were assessed on hepatic metabolism by examining adiposity and inflammation in the adipose and liver of the 90-day male offspring. Pregnant Wistar rats were exposed to BPA and BPS (0.0, 0.4, 4.0 {micro}g/kg bw) via gavage from gestational day 4 to 21. Prenatal BPS-exposed offspring exhibited a higher obesogenic effect than BPA, including changes in body weight, body fat, feed efficiency, and leptin signalling. The fasting blood glucose did not change, but BPS exposure elevated plasma corticosterone levels and adipocyte hypertrophy of the visceral adipose tissue (VAT) to a greater extent than BPA. Adipocyte hypertrophy was augmented by modulated expression of lipid uptake (PPAR{gamma}, FABP4), glucocorticoid (HSD11{beta}1), inflammation (IL6, IL1{beta}, CRP, COX2), oxidative stress (CHOP) and apoptotic (Caspase 3) mediators. Liver histology showed numerous lipid droplets, and hepatocyte ballooning, associated with upregulated expression of cholesterol, lipid biogenesis and glucocorticoid activators, indicating microvesicular steatosis in the prenatally BPS-exposed adult offspring. The upregulated PPAR, ADRP, and FGF21 expression and increased lipid peroxidation in the offsprings liver suggest metaflammation due to fetal exposure to BPS. Fetal BPS exposure demonstrated a more significant disruption in metabolism involving adiposity, liver fat, inflammation in excess, and predisposition to hepatic steatosis in the male offspring. HighlightsO_LIFetal BPS exposure exhibited enlarged and inflamed adipocytes more than BPA C_LIO_LIPrenatal BPS exposure induced excess lipid droplets & hepatocyte ballooning in liver C_LIO_LIIn utero exposure to BPS induces microvesicular steatosis in adult rats C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/543354v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@89c53org.highwire.dtl.DTLVardef@14f176borg.highwire.dtl.DTLVardef@18a934corg.highwire.dtl.DTLVardef@cc7af6_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2023

Fetal exposure to endocrine disrupting-bisphenol A (BPA) alters testicular fatty acid metabolism in the adult offspring: relevance to sperm maturation and quality

Daily exposure to bisphenols can affect reproductive functions due to their pseudo-estrogenic and/or anti-androgenic effects. Testicular lipids contain high levels of polyunsaturated fatty acids necessary for sperm maturity, motility, and spermatogenesis. Whether prenatal exposure to bisphenols alters testicular fatty acid metabolism in adult offspring is unknown. Pregnant Wistar rats were gavaged from gestational day 4 to 21 with BPA and BPS (0.0, 0.4, 4.0, 40.0 g/kg bw/d). Despite increased body and testis weight, the total testicular cholesterol, triglyceride, and plasma fatty acids were unaffected in offspring. Lipogenesis was upregulated by increased SCD-1, SCD-2, and expression of lipid storage (ADRP) and trafficking protein (FABP4). The arachidonic acid, 20:4 n-6 (ARA) and docosapentaenoic acid, 22:5 n-6 (DPA) levels were decreased in the BPA-exposed testis, while BPS exposure had no effects. The expression of PPAR, PPAR{gamma} proteins and CATSPER2 mRNA were decreased, which are important for energy dissipation and motility of the sperm in the testis. The endogenous conversion of linoleic acid,18:2n-6 (LA), to ARA was impaired by a reduced ARA/LA ratio and decreased FADS1 expression in BPA-exposed testis. Collectively, fetal BPA exposure affected endogenous long-chain fatty acid metabolism and steroidogenesis in the adult testis, which might dysregulate sperm maturation and quality. HighlightsO_LIIn utero BPA exposure not BPS affected testicular long-chain n-6 PUFA metabolism in offspring C_LIO_LIFetal exposure to BPA alters delta-9-desaturase indices in the adult testis C_LIO_LIBPA exposure reduced fatty acid desaturase1 expression in offspring testis C_LIO_LIFetal BPA exposure dysregulated lipogenesis in offspring testis C_LI

developmental biology↗