ERß Regulation of Indian Hedgehog Expression in the First Wave of Ovarian Follicles.

Increased activation of ovarian primordial follicles in Erß knockout (ErßKO) rats becomes evident as early as postnatal day 8.5. To identify the ERß-regulated genes that may control ovarian primordial follicle activation, we analyzed the transcriptome profiles of ErßKO rat ovaries collected on postnatal days 4.5, 6.5, and 8.5. Compared to wildtype ovaries, ErßKO ovaries displayed dramatic downregulation of Indian hedgehog (Ihh) expression. IHH-regulated genes, including Hhip, Gli1, and Ptch1, were also downregulated in ErßKO ovaries. This was associated with a downregulation of steroidogenic enzymes Cyp11a1, Cyp19a1, and Hsd17b1. The expression of Ihh remained very low in ErßKO ovaries despite the high levels of Gdf9 and Bmp15, which are known upregulators of Ihh expression in the granulosa cells of activated ovarian follicles. Strikingly, the downregulation of the Ihh gene in ErßKO ovaries began to disappear on postnatal day 16.5 and recovered on postnatal day 21.5. In rat ovaries, the first wave of primordial follicles is rapidly activated after their formation, whereas the second wave of primordial follicles remains dormant in the ovarian cortex and slowly starts activating after postnatal day 12.5. We localized the expression of Ihh mRNA in postnatal day 8.5 wildtype rat ovaries but not in the age-matched ErßKO ovaries. In postnatal day 21.5 ErßKO rat ovaries, we detected Ihh mRNA mainly in the activated follicles in the ovaries' peripheral regions. Our findings indicate that the expression of Ihh in the granulosa cells of the activated first wave of ovarian follicles depends on ERß.

Loss of ERß Disrupts Gene Regulation in Primordial and Primary Follicles.

Loss of ERß increases primordial follicle growth activation (PFGA), leading to premature ovarian follicle reserve depletion. We determined the expression and gene regulatory functions of ERß in dormant primordial follicles (PdFs) and activated primary follicles (PrFs) using mouse models. PdFs and PrFs were isolated from 3-week-old Erß knockout (Erßnull) mouse ovaries, and their transcriptomes were compared with those of control Erßfl/fl mice. We observed a significant (≥2-fold change; FDR p-value ≤ 0.05) deregulation of approximately 5% of genes (866 out of 16,940 genes, TPM ≥ 5) in Erßnull PdFs; ~60% (521 out of 866) of the differentially expressed genes (DEGs) were upregulated, and 40% were downregulated, indicating that ERß has both transcriptional enhancing as well as repressing roles in dormant PdFs. Such deregulation of genes may make the Erßnull PdFs more susceptible to increased PFGA. When the PdFs undergo PFGA and form PrFs, many new genes are activated. During PFGA of Erßfl/fl follicles, we detected a differential expression of ~24% genes (4909 out of 20,743; ≥2-fold change; FDR p-value ≤ 0.05; TPM ≥ 5); 56% upregulated and 44% downregulated, indicating the gene enhancing and repressing roles of Erß-activated PrFs. In contrast, we detected a differential expression of only 824 genes in Erßnull follicles during PFGA (≥2-fold change; FDR p-value ≤ 0.05; TPM ≥ 5). Moreover, most (~93%; 770 out of 824) of these DEGs in activated Erßnull PrFs were downregulated. Such deregulation of genes in Erßnull activated follicles may impair their inhibitory role on PFGA. Notably, in both Erßnull PdFs and PrFs, we detected a significant number of epigenetic regulators and transcription factors to be differentially expressed, which suggests that lack of ERß either directly or indirectly deregulates the gene expression in PdFs and PrFs, leading to increased PFGA.

Role of Dietary Supplements in Thyroid Diseases.

BACKGROUND: Thyroid hormones play a vital role in regulating our body's metabolism. Two important thyroid hormones released from the thyroid gland are tri-iodothyronine (T3) and tetra-iodothyronine (T4). Thyroid-stimulating hormone and thyroid regulating hormone control the T3 and T4 levels in our body. Increased TSH levels indicate hypothyroidism and decreased TSH levels indicate hyperthyroidism. Iodine is a crucial nutrient for the synthesis of thyroid hormones and is mostly obtained from our diet. Other essential nutrients for the thyroid hormones formation include selenium, iron, vitamin D, vitamin B12, etc. Dietary changes in these nutrients can result in alterations in thyroid function and structure. Although normally, the hormonal diseases cannot be cured, but we can improve their signs and symptoms using suitable dietary supplements. OBJECTIVE: The aim of the study was to thoroughly analyze the various benefits and risks associated with the use of dietary supplements for the prevention and treatment of various thyroid disorders, like hypothyroidism, as seen in Hashimoto's thyroiditis; hyperthyroidism, as seen in Graves' disease; sick euthyroidism and subclinical hypothyroidism. METHODS: Literature was searched using the search terms "dietary supplements+thyroid diseases" on Pubmed, Google Scholar, Scopus, Cochrane Library, and other search engines, and data were collected from 1967 to November, 2021, including research inputs from the authors. The literature was thoroughly searched, and deep knowledge was acquired on this topic, which was then sequentially organized and summarized using suitable tables and figures. CONCLUSION: After analyzing various studies on this topic, we arrived at the conclusion that although there are various claimed and observed health benefits of dietary supplements in the prevention and treatment of various thyroid disorders, still several studies have shown too many risks to be associated with the use of dietary supplements, and people using these products should be aware of these risks in order to use them very judiciously for the improvement of their thyroid status.

Lead Anti-Obesity Compounds from Nature.

BACKGROUND: Obesity has become a global issue, leading to increased risk of metabolic syndrome, which encompasses diabetes, cardiovascular disease, stroke, hypertension, and certain cancers. However, obesity is difficult to control through diet and exercise alone, as they are difficult to implement. OBJECTIVE: The objective of this review is to elucidate the active constituents that can be obtained from various natural sources that act as anti-obesity agents. Due to the global rise in the prevalence of obesity, an urgent need to prevent and control it has arisen. METHODS: For this review, we compiled information about natural anti-obesity products through an electronic search of the articles available via PubMed, Scopus, and other internet sources for the period 1975-2019 and included our own research. We analyzed and organized data on various natural products in popular use in addition to relevant pharmacognostic and biological studies. The products' mechanisms of action were also investigated. CONCLUSION: Consumption of diets that include high amounts of active anti-obesity natural compounds is a promising strategy for the suppression of lipid accumulation and adipogenesis in obese individuals.