The time for ambitious action is now: Science-based recommendations for plastic chemicals to inform an effective global plastic treaty.

The ubiquitous and global ecological footprint arising from the rapidly increasing rates of plastic production, use, and release into the environment is an important modern environmental issue. Of increasing concern are the risks associated with at least 16,000 chemicals present in plastics, some of which are known to be toxic, and which may leach out both during use and once exposed to environmental conditions, leading to environmental and human exposure. In response, the United Nations member states agreed to establish an international legally binding instrument on plastic pollution, the global plastics treaty. The resolution acknowledges that the treaty should prevent plastic pollution and its related impacts, that effective prevention requires consideration of the transboundary nature of plastic production, use and pollution, and that the full life cycle of plastics must be addressed. As a group of scientific experts and members of the Scientists' Coalition for an Effective Plastics Treaty, we concur that there are six essential "pillars" necessary to truly reduce plastic pollution and allow for chemical detoxification across the full life cycle of plastics. These include a plastic chemical reduction and simplification, safe and sustainable design of plastic chemicals, incentives for change, holistic approaches for alternatives, just transition and equitable interventions, and centering human rights. There is a critical need for scientifically informed and globally harmonized information, transparency, and traceability criteria to protect the environment and public health. The right to a clean, healthy, and sustainable environment must be upheld, and thus it is crucial that scientists, industry, and policy makers work in concert to create a future free from hazardous plastic contamination.

A survey of epibiont hydrozoans on Sargassum.

The brown alga Sargassum provides a natural substrate occupied by hydrozoans in shallow marine waters. A global count in 2007 listed 39 epibiotic species of Hydrozoa growing on Sargassum, but more studies have been published since, therefore, an update is timely, particularly due to the increased abundance of Sargassum in the Caribbean. This review, based on a recent literature survey and new records from Mexico, includes 133 publications of epibiotic hydrozoans on Sargassum spanning 220 years, from 1802 to 2022. A total of 131 hydrozoan species were recorded on 26 species of Sargassum, most belonging to the subclass Hydroidolina (130), with only one record of a trachyline medusa (Gonionemus vertens, subclass Trachylinae). Most publications centered on the Tropical Atlantic, where the greatest number of hydrozoan species (67 species) were recorded. All hydrozoan species possess a hydrorhiza, except one hydromedusae species that attach to Sargassum via adhesive tentacles. Most of the hydrozoan species associated with Sargassum exhibited a benthic life cycle (93 species) and are comprised of erect, branched colonies (67 species) and large hydrothecae (69 species). Although the number of studies of epibiotic hydrozoans on Sargassum has increased since the mid-20th century, nevertheless hydrozoan richness has not reached an asymptote. Therefore, more sampling of Sargassum species would likely identify more hydrozoan species associated with Sargassum, especially among benthic Sargassum, and might help reveal potential biogeographical and ecological patterns between Sargassum and hydrozoan epibionts.

Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.

Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms.

Neonatal exposure to bisphenol A alters the hypothalamic-pituitary-thyroid axis in female rats.

Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many common products. Several reports revealed potent in vivo and in vitro effects. In this study we analyzed the effects of the exposure to BPA in the hypothalamic-pituitary-thyroid axis in female rats, both in vivo and in vitro. Female Sprague-Dawley rats were injected sc from postnatal day 1 (PND1) to PND10 with BPA: 500 µg 50 µl-1 oil (B500), or 50 µg 50 µl-1 (B50), or 5 µg 50 µl-1 (B5). Controls were injected with 50 µl vehicle during the same period. Neonatal exposure to BPA did not modify TSH levels in PND13 females, but it increased them in adults in estrus. Serum T4 was lower in B5 and B500 with regards to Control, whereas no difference was seen in T3. No significant differences were observed in TRH, TSHß and TRH receptor expression between groups. TSH release from PPC obtained from adults in estrus was also higher in B50 with regard to Control. In vitro 24 h pre-treatment with BPA or E2 increased basal TSH as well as prolactin release. On the other hand, both BPA and E2 lowered the response to TRH. The results presented here show that the neonatal exposure to BPA alters the hypothalamic pituitary-thyroid axis in adult rats in estrus, possibly with effects on the pituitary and thyroid. They also show that BPA alters TSH release from rat PPC through direct actions on the pituitary.

Astrocyte-Specific Deletion of Peroxisome-Proliferator Activated Receptor-γ Impairs Glucose Metabolism and Estrous Cycling in Female Mice.

Mice lacking peroxisome-proliferator activated receptor-γ (PPARγ) in neurons do not become leptin resistant when placed on a high-fat diet (HFD). In male mice, this results in decreased food intake and increased energy expenditure, causing reduced body weight, but this difference in body weight is not observed in female mice. In addition, estrous cycles are disturbed and the ovaries present with hemorrhagic follicles. We observed that PPARγ was more highly expressed in astrocytes than neurons, so we created an inducible, conditional knockout of PPARγ in astrocytes (AKO). The AKO mice had impaired glucose tolerance and hepatic steatosis that did not worsen with HFD. Expression of gluconeogenic genes was elevated in the mouse livers, as was expression of several genes involved in lipogenesis, lipid transport, and storage. The AKO mice also had a reproductive phenotype with fewer estrous cycles, elevated plasma testosterone levels, reduced corpora lutea formation, and alterations in hypothalamic and ovarian gene expression. Thus, the phenotypes of the AKO mice were very different from those seen in the neuronal knockout mice, suggesting distinct roles for PPARγ in these two cell types.

Obese Neuronal PPARγ Knockout Mice Are Leptin Sensitive but Show Impaired Glucose Tolerance and Fertility.

The peroxisome-proliferator activated receptor γ (PPARγ) is expressed in the hypothalamus in areas involved in energy homeostasis and glucose metabolism. In this study, we created a deletion of PPARγ brain-knockout (BKO) in mature neurons in female mice to investigate its involvement in metabolism and reproduction. We observed that there was no difference in age at puberty onset between female BKOs and littermate controls, but the BKOs gave smaller litters when mated and fewer oocytes when ovulated. The female BKO mice had regular cycles but showed an increase in the number of cycles with prolonged estrus. The mice also had increased luteinizing hormone (LH) levels during the LH surge and histological examination showed hemorrhagic corpora lutea. The mice were challenged with a 60% high-fat diet (HFD). Metabolically, the female BKO mice showed normal body weight, glucose and insulin tolerance, and leptin levels but were protected from obesity-induced leptin resistance. The neuronal knockout also prevented the reduction in estrous cycles due to the HFD. Examination of ovarian histology showed a decrease in the number of primary and secondary follicles in both genotypes due to the HFD, but the BKO ovaries showed an increase in the number of hemorrhagic follicles. In summary, our results show that neuronal PPARγ is required for optimal female fertility but is also involved in the adverse effects of diet-induced obesity by creating leptin resistance potentially through induction of the repressor Socs3.

Free fatty acids induce Lhb mRNA but suppress Fshb mRNA in pituitary LßT2 gonadotropes and diet-induced obesity reduces FSH levels in male mice and disrupts the proestrous LH/FSH surge in female mice.

Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction. We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production. FFAs caused a time- and dose-dependent increase in phosphorylation of the MAPKs p38MAPK, c-Jun N-terminal kinase (JNK)-1/2, and ERK1/2 in LßT2 gonadotrope cells. Furthermore, FFAs up-regulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling. FFAs enhanced the activation of the MAPKs in the presence of GnRH, although the cotreatment did not alter Lhb induction but did eliminate the GnRH induction of Fshb. FFAs also suppressed activin-induced Fshb expression. Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via toll-like receptor-2 and toll-like receptor-4 and was mimicked by lipopolysaccharide stimulation. In vivo, male C57BL/6 mice on a high-fat diet showed reduced FSH levels consistent with the suppression of Fshb seen in vitro. Histological analysis of the testes showed an increased number of abnormal seminiferous tubules. Female mice on a high-fat diet lacked the expected proestrus LH and FSH surge and exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea. Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.

Gonadotropin-releasing hormone signaling pathways in an experimental ovarian tumor.

Previous results showed that GnRH signaling is altered in cells from rat luteinized ovarian tumors (tumor group) because it did not activate the phospholipase C pathway, in contrast to control ovarian cells from superovulated prepubertal rats (SPO). In the present work, alternate GnRH-induced second messengers such as phospholipase A(2) and phospholipase D activation, cAMP production, ERK1/2 phosphorylation, and the presence of G proteins were evaluated to determine GnRH mechanism of action in tumor cells. G proteins examined were present in both cell types. Buserelin, a GnRH agonist, (1, 10, and 100 ng/ml) increased phosphatidylethanol in SPO, indicating phospholipase D activation. Only 100 ng/ml buserelin induced a significant response in the tumor group. Buserelin (100 ng/ml) increased (3)H-arachidonic acid in culture media in SPO, indicating phospholipase A(2) activation; no effect was observed in the tumor group. Buserelin (100 and 1000 ng/ml) induced pertussis toxin-insensitive cAMP increases in both cell types, with similar potencies. In the tumor group, buserelin (100 ng/ml) inhibited human chorionic gonadotropin-induced cAMP and progesterone; this effect was protein kinase C (PKC) dependent (inhibited by GF109203X, a PKC inhibitor). Buserelin (100 and 1000 ng/ml) induced ERK1/2 phosphorylation in both cell kinds. Buserelin-induced ERK1/2 activation was G(i/0) independent and PKC dependent. Only in the tumor group, buserelin-induced ERK1/2 activation was cAMP dependent (abolished by SQ 22536, the adenylyl cyclase inhibitor). Furthermore, dibutyryl cAMP-induced ERK1/2 activation in the tumor group was PKC dependent (inhibited by GF109203X). In conclusion, activation of phospholipases in tumor cells does not seem to mediate GnRH effects. GnRH signaling seems to involve adenylyl cyclase activation, PKC stimulation, and ERK1/2 phosphorylation.