The Importance of Fostering and Funding Scientific Research, and its Relevance to Environmental Toxicology and Chemistry.

What do environmental contaminants and climate change have in common with the virus SARS-CoV-2 and the disease COVID-19? We argue that one common element is the wealth of basic and applied scientific research that provides the knowledge and tools essential in developing effective programs for addressing threats to humans and social-ecological systems. Research on various chemicals, including dichlorodiphenyltrichloroethane and per- and polyfluoroalkyl substances, resulted in regulatory action to protect environmental and human health. Moreover, decades of research on coronaviruses, mRNA, and recently SARS-CoV-2 enabled the rapid development of vaccines to fight the COVID-19 pandemic. In the present study, we explore the common elements of basic and applied scientific research breakthroughs that link chemicals, climate change, and SARS-CoV-2/COVID-19 and describe how scientific information was applied for protecting human health and, more broadly, socio-ecological systems. We also offer a cautionary note on the misuse and mistrust of science that is not new in human history, but unfortunately is surging in modern times. Our goal was to illustrate the critical role of scientific research to society, and we argue that research must be intentionally fostered, better funded, and applied appropriately. To that end, we offer evidence that supports the importance of investing in scientific research and, where needed, ways to counter the spread of misinformation and disinformation that undermines legitimate discourse. Environ Toxicol Chem 2023;42:581-593. © 2022 SETAC.

Progestin exposure before gonadotropin stimulation improves embryo development after in vitro fertilization in the domestic cat.

This study investigated the influence of progestin priming and ovarian quiescence on response to exogenous gonadotropin stimulation in the cat. Because a subpopulation of cats routinely ovulated spontaneously, there also was the opportunity to examine the ovary's reaction to the added impact of endogenously secreted progestagen. Queens were given 1) equine chorionic gonadotropin (eCG) plus human chorionic gonadotropin (hCG) only (control; n = 9 cats), 2) GnRH antagonist (antide) injections followed by eCG and hCG (n = 9), and 3) a progestin implant (levonorgestrel) followed by eCG and hCG (n = 9). Laparoscopy was used to assess ovarian activity and aspirate follicular oocytes that were graded on the basis of morphology. In five cats per treatment, half of the high-quality oocytes were assessed for glucose, pyruvate, and lactate metabolism as well as nuclear maturation. Remaining oocytes were inseminated in vitro, cultured, and examined at 72 h after insemination for cleavage. In the remaining four cats per treatment, all oocytes were inseminated in vitro and assessed at 72, 120, and 168 h after insemination for embryo developmental stage. Cats pretreated with progestin had more follicles and produced more embryos per donor (including at the combined morula/blastocyst stage) than controls or females treated with GnRH antagonist (P < 0.05). There were no differences among groups (P > 0.05) in oocyte carbohydrate metabolism, nuclear maturation metrics, or fertilization success, although there was a tendency toward improvements in all three (P < 0.2) in progestin-treated females. Interestingly, cats that spontaneously ovulated within 60 days of treatment onset also produced more embryos per cat than induced-ovulation counterparts (P < 0.05). Results indicate that prior exposure to exogenous progestin (via implant) or endogenous progestagen (via spontaneous ovulation) improves ovarian responsiveness to gonadotropins in the cat through a mechanism that is independent of the induction of ovarian quiescence.

Priming with progestin, but not GnRH antagonist, induces a consistent endocrine response to exogenous gonadotropins in induced and spontaneously ovulating cats.

Ovarian sensitivity to exogenous gonadotropin stimulation (equine chorionic gonadotropin [eCG] and human chorionic gonadotropin [hCG]) following pre-treatment with a progestin (levonorgestrel) versus GnRH antagonist (antide) was studied in cats known to be induced versus spontaneous ovulators. Queens were assigned to one of three treatments: (1) levonorgestrel implants+eCG/hCG (n=7 cats); (2) antide injections+eCG/hCG (n=7) or (3) eCG/hCG alone (control; n=7). Hormonal metabolites were assessed in fecal samples collected daily for 60 days before and during the 37 days inhibitory pre-treatment and for more than 60 days after eCG/hCG. Fecal metabolites of estradiol and progesterone were measured by radioimmunoassay. Females that maintained baseline progesterone were considered induced ovulators, whereas cats that exhibited a luteal phase before inhibition treatment were classified as spontaneous ovulators. Based on fecal hormone profiles, levonorgestrel thoroughly inhibited ovarian activity, whereas antide synchronized follicular phases but did not induce complete ovarian down-regulation. Both treatments prevented ovulation in spontaneous ovulators, but neither caused regression of existing corpora lutea (CL). Levonorgestrel, but not antide, pre-treatment resulted in a quiescent ovary at the time of eCG injection, yet endocrine responses to eCG/hCG were not different among treatments. Interestingly, spontaneously ovulating females exhibited a prolonged estradiol response to gonadotropin stimulation compared to induced ovulators, and this prolonged estradiol surge was replicated by levonorgestrel pre-treatment. Thus, the progestin levonorgestrel effectively suppresses follicular and luteal activity in the cat, resulting in a more consistent response to gonadotropin stimulation, even in females prone to spontaneous ovulation.

Effects of dose and glycosylation on the transfer of genistein into the eggs of the Japanese quail (Coturnix japonica).

Soy isoflavones have been associated with several beneficial effects of soy in human diets. However, most soy is consumed by livestock in the Western countries. It is possible that isoflavones could be transferred and/or accumulated into animal products, which could become additional sources of dietary isoflavones for humans. Our objectives were to determine whether dietary isoflavone genistein could be transferred and/or accumulated into the eggs of Japanese quail (Coturnix japonica) and how the supplementation dosage and glycosylation of the isoflavone would affect this transfer. Adult reproductive female Japanese quail were randomly assigned to treatment groups that received encapsulated 50 or 100 mg genistein or 80 mg genistin per day (four quail per treatment) for 5 days. A control group (two quail) received placebo capsules. Eggs were collected prior to treatment and then daily for 15 days. The egg, separated into yolk and white, and pulverized quail diet were extracted in 80% methanol for 2 h and either centrifuged or filtered before evaporation of the solvent. The extracts were redissolved in 16% acetonitrile for high-performance liquid chromatography (HPLC) analyses. Genistein and genistein metabolites were detected in the egg yolks of treated quail. Trace concentrations of genistein were detected in the control group, due to the presence of genistein derivatives in the diet. Neither genistein nor its metabolites were found in egg white. Levels of genistein in the eggs increased significantly from the 3rd day of supplementation and reached the maximum about 2 days after the supplementation stopped. The higher dose of genistein supplementation resulted in higher genistein concentrations in egg yolks. Glycosylation decreased the transfer and accumulation of genistein into the egg yolks.