There is emerging evidence demonstrating an association between maternal polycystic ovary syndrome (PCOS) and autism spectrum disorder (ASD) in children, however, the cumulative effect of maternal PCOS on the development of ASD or other neuropsychiatry disorders (NPD) in children and separately for males and females has not been examined. We sought to systematically evaluate the influence of maternal PCOS on a wide range of NPD including ASD, attention deficit hyperactivity disorder (ADHD), chronic tic disorder (CDT), other behavior disorders, anxiety, depression, bipolar disorder, schizophrenia in children as well as in women of reproductive age only. We queried electronic databases including PubMed, EMBASE, and Google Scholar, until March 2021. We used DerSimonian and Laird (D-L) random effects method to compute pooled effect size in terms of odds ratio (OR). Nineteen studies (1667851 mothers, 2260622 children) were included in this study. Mothers with PCOS had an increased odds of children diagnosed with ASD (OR = 1.40, p < 0.001), ADHD (OR = 1.42, p < 0.001), CTD (OR = 1.44, p = 0.001), anxiety (OR = 1.33, p < 0.001), as well as other behavioral symptoms (OR = 1.45, p < 0.001) in the adjusted analysis. The association between maternal PCOS and ASD (OR: 1.43 vs. 1.66), ADHD (OR: 1.39 vs. 1.54), and CTD (OR: 1.42 vs. 1.51) was found to be significantly consistent between males and females, respectively. Our data do not suggest increased fetal testosterone exposure is associated with increased autistic traits in children. However, PCOS was significantly associated with increased odds of a wide range of NPD in women themselves. Maternal PCOS is a risk factor for various NPD with a similar extent in their children regardless of their underlying comorbidities. Managing PCOS is essential for women’s health as well as for their children’s health. More research is needed to determine the mechanisms and links between maternal PCOS and NPD in children.

Hepatocellular carcinoma (HCC) is the most abundant form of liver cancer. It accounts for 75–85% of liver cancer cases and, though it ranks globally as the sixth most common cancer, it ranks second in cancer-related mortality. Deaths from HCC are usually due to metastatic spread of the cancer. Unfortunately, there are many challenges and limitations with the latest HCC therapies and medications, making it difficult for patients to receive life-prolonging care. As there is clearly a high demand for alternative therapy options for HCC, it is prudent to turn to plants for the solution, as their phytochemicals have long been used and revered for their many medicinal purposes. This review explores the promising phytochemical compounds identified from pre-clinical and clinical trials being used either independently or in conjunction with already existing cancer therapy treatments. The phytochemicals discussed in this review were classified into several categories: lipids, polyphenols, alkaloids, polysaccharides, whole extracts, and phytochemical combinations. Almost 80% of the compounds failed to progress into clinical studies due to lack of information regarding the toxicity to normal cells and bioavailability. Although large obstacles remain, phytochemicals can be used either as an alternative or integrative therapy in conjunction with existing HCC chemotherapies. In conclusion, phytochemicals have great potential as treatment options for hepatocellular carcinoma.

Early full-term pregnancy is known to reduce the lifetime risk of breast cancer. Although the phenomenon of parity-induced protection is well-established, the physiological mechanisms involved in this protection are not clear. Earlier reports have shown that pregnancy results in alterations of hormone levels. How pregnancy affects hypothalamic hormones and how the change, if any, influences breast cancer is not well understood. Seven-week-old female Lewis rats were given N-methyl-N-nitrosourea. Two weeks post carcinogen exposure, a set of females were housed with males to generate the parous rats and another set of rats served as the nulliparous controls. Mammary tumorigenesis was assessed for 9 months. Hypothalamic and pituitary levels of hormones were measured at various timepoints. Further, animals were also challenged with growth hormone and prolactin secretagogues to test the effect of pregnancy on the hypothalamic–pituitary hormonal axis. Persistent alterations in the level of growth hormone-releasing hormone, thyrotropin releasing hormone, dopamine, and somatostatin in the hypothalamus of parous animals was observed. Further, we also observed that pregnancy had a significant effect on the pituitary gland and its response to growth hormone and prolactin secretagogues. Our studies using the rodent model system demonstrate that pregnancy could be reducing the risk of breast cancer by persistently altering the hypothalamic–pituitary axis, which could have implications for breast cancers in humans as well.

Introduction: Parous rats treated with chemical carcinogen develop a low incidence of overt mammary cancers compared to that in carcinogen-treated nulliparous rats. Examination of the mammary glands at necropsy 12 months after carcinogen treatment revealed that a high percentage of the parous rats had preneoplastic mammary lesions. These studies demonstrate that in parous rats, initiation of mammary carcinogenesis occurs at a high efficiency, although the systemic and local environment is inadequate for promotion to overt cancers. Stem cells have been implicated as the target cells for tumor initiation. In this study we investigated if parity altered the mammary stem cells. Materials and Methods: Nulliparous and parous parous were euthanized and the preneoplastic mammary lesions were surgically removed under a dissection microscope. The lesions were dissociated using the collagenase digestion method. After digestion the cells were separated using the percoll gradient. The enriched epithelial cell population was cultured and sorted for stem cells using ALDH, CD44, CD24 as markers. Sphere formation assays was established using 5000 cells/well on ultra-low attachment 6-well plates. For self-renewal assay, the 1st generation spheres was dissociated using Accutase, counted and replated in the same media as single cells with a plating density of 5000 cells/well. The same process was followed for the subsequent generations. In another set of experiments stem cells were treated with growth hormone (GH) and prolactin (PRL) to identify the role of these two mammogenic hormones on the mammary stem cells. Using the stem cells we performed the limiting dilution analysis to estimate the tumor forming capacity of the initiated mammary stem cells. Results: The sphere forming capacity of parous mammary stem cells was significantly reduced compared to nulliparous mammary stem cells. In addition, the self-renewing abilities were also remarkably decreased. Treatment with GH and PRL restored the sphere forming and self-renewing capabilities of parous mammary stem cells similar to nulliparous mammary stem cells. Further, the limiting dilution assay also demonstrated that parity altered the mammary stem cells making them less capable of forming tumors. Conclusion: Parity significantly altered the characteristics of the mammary stem cells rendering them to be resistant to mammary tumorigenesis. GH and PRL were able to increase stemness and favor mammary tumorigenesis in parous rats. Further research is required to delineate the mechanism by which parity alters the stemness characteristics of mammary stem cells reducing the risk of mammary cancers. Citation Format: Ramadevi Subramani, Adriana Estrada, Sheryl Rodriguez, Seeta Poudel, Jesse Foskey, Cynthia Jimenez, Kenneth Smith, Mark Shahinian, Abdallah Yazadi, Tugba Mehmetoglu-Gurbuz, Jackelyn Rocha, Rajkumar Lakshmanaswamy. Parity reduces the risk of mammary cancer by altering the characteristics of mammary stem cells [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-11-02.