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A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno‐miR‐184 and rno‐miR‐141‐3p in the ventral prostate (VP) of offspring. Here, rno‐miR‐184 and rno‐miR‐141‐3 expressions were obtained by RT‐qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21‐F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 μg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1‐treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hairdressers constitute a major occupational group of female workers who are exposed to chemicals that cause reproductive abnormalities in animal models. The purpose of this study was to examine whether hairdressers are at increased risk of premature ovarian failure (POF) compared with women of similar age in other occupations. [ABSTRACT FROM PUBLISHER]

Objective Studies have reported a decline in sexual functioning among women undergoing the menopausal transition. Few studies, however, have examined the associations between hormones and sexual dysfunction during this time period. Therefore, the purpose of this study was to examine the associations between participant characteristics and endogenous hormones with sexual functioning in mid-life women. Methods Data were analyzed from a community-based sample of 441 women aged 45-54 years who stated that they were sexually active at the time of the study. Each participant completed a survey that included questions pertaining to sexual functioning and provided a blood sample that was used to measure estrogen and androgen concentrations. Results Among women who reported being sexually active, poorer self-reported health and the experiencing of depressive symptoms were significantly associated with not being satisfied with sexual relations after adjustment for other covariates. None of the hormones examined were significantly associated with overall sexual satisfaction. However, statistically significant associations between both total testosterone levels and the free testosterone index with satisfaction with the frequency of sexual relations were observed. Conclusions Our findings indicate that the experiencing of depressive symptoms and the reporting of poor overall health are important correlates of sexual dysfunction. Further, our results suggest that higher total and free testosterone levels are significantly associated with a desire for increased frequency of sexual relations among mid-life women. [ABSTRACT FROM AUTHOR]

Selective induction of cell death is a means to remove unwanted cell populations from a tissue or organ. Understanding the signalling events responsible for mediating cell death by cytokines, such as tumor necrosis factor-alpha (TNFα) are key to the development of pharmacologic inducers of this response. Ceramide has been implicated as a secondary messenger for TNFα-induced cell death, but many of the intracellular effects of ceramide are not fully understood. Recent reports suggest that ceramide signaling may involve oxidative stress. To explore the relationship between TNF sensitivity and ceramide signaling, two genetic variants of mouse JB6 RT101 epidermal tumor cells, one resistant and one sensitive to TNFα- induced cytotoxicity, were treated with C2-ceramide. Treatment with 20 μM ceramide induced apoptosis and this was quickly followed by oncotic necrosis in the TNFα-sensitive JB6 (TNFs) cells. The same concentration of ceramide induced apoptosis, but not oncotic necrosis of the TNFα resistant JB6 (TNFr) cells. The basal level of glutathione was significantly higher in TNFr cells than in TNFs cells. Treatment with 20 μM ceramide decreased cellular glutathione in TNFs cells by 50%, in contrast to an insignificant decrease in the TNFr cells. A significant increase in reactive oxygen was noted in TNFs cells treated with 10 or 20 μM ceramide. Furthermore, pretreatment with the antioxidant N-acetylcysteine or with glutathione monoethylester delayed the onset of ceramide-induced oncotic necrosis, but did not inhibit apoptosis. Our results suggest that the severity of the decrease in glutathione appears to determine whether cells undergo just apoptosis or also oncotic necrosis. They also suggest that ceramide-induced oncotic necrosis is modulated by a decline in cellular glutathione and an elevation of reactive oxygen. These results suggest that a decrease in cellular redox potential determines susceptibility to ceramide-dependent killing pathways. [ABSTRACT FROM PUBLISHER]

As the second leading cause of death for cancer among men worldwide, prostate cancer (PCa) prevention and detection remain a critical challenge. One aspect of PCa research is the identification of common environmental agents that may increase the risk of initiation and progression of PCa. Endocrine disrupting chemicals (EDCs) are strong candidates for risk factors, partially because they alter essential pathways for prostate gland development and oncogenesis. Phthalates correspond to a set of commercially used plasticizers that humans are exposed to ubiquitously. Here, we show that maternal exposure to a phthalate mixture interferes with the expression profile of mRNA and proteins in the ventral prostate of offspring and increases the susceptibility to prostate adenocarcinomas in aged animals. The data highlight Ubxn11, Aldoc, Kif5c, Tubb4a, Tubb3, Tubb2, Rab6b and Rab3b as differentially expressed targets in young and adult offspring descendants (PND22 and PND120). These phthalate-induced targets were enriched for pathways such as: dysregulation in post-translational protein modification (PTPM), cell homeostasis, HSP90 chaperone activity, gap junctions, and kinases. In addition, the Kif5c, Tubb3, Tubb2b and Tubb4a targets were enriched for impairment in cell cycle and GTPase activity. Furthermore, these targets showed strong relationships with 12 transcriptional factors (TF), which regulate the phosphorylation of eight protein kinases. The correlation of TF-kinases is associated with alterations in immune system, RAS/ErbB/VEGF/estrogen/HIF-1 signaling pathways, cellular senescence, cell cycle, autophagy, and apoptosis. Downregulation of KIF5C, TUBB3 and RAB6B targets is associated with poor prognosis in patients diagnosed with adenocarcinoma. Collectively, this integrative investigation establishes the post-transcriptional mechanisms in the prostate that are modulated by maternal exposure to phthalate mixture during gestation and lactation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Retinoids are essential for reproduction. Most research has focused on the role of retinoic acid signaling in the regulation of meiosis during early fetal germ cell development. However, less attention has been paid to the possible effects of retinoic acid signaling in adult female gonads. Retinoic acid, its receptors, and the key enzymes required for retinoic acid synthesis are expressed in the ovaries and they are involved in the regulation of folliculogenesis and steroidogenesis. Exposure to compounds that can interfere with normal retinoic acid signaling is associated with adverse ovarian outcomes, including altered steroidogenesis and reduction in indicators of ovarian reserve in women and laboratory animal models. These observations call for more attention to retinoids as regulators of adult ovarian physiology and as possible targets of endocrine disruption by environmental chemicals. In this review, we summarize the current knowledge of retinoids in folliculogenesis and steroidogenesis in post-pubertal mammalian ovaries., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The aryl hydrocarbon receptor (AHR) mediates the toxic effects of various endocrine disrupting chemicals. In female mice, global deletion of the Ahr (AhrKO) results in slow growth of ovarian antral follicles. No studies, however, have examined whether injection of the Ahr restores the phenotypes of cultured AhrKO ovarian antral follicles to wild-type levels., Methods: We developed a system to construct a recombinant adenovirus containing the Ahr to re-express the Ahr in AhrKO granulosa cells and whole antral follicles. We then compared follicle growth and levels of factors in the AHR signaling pathway (Ahr, Ahrr, Cyp1a1, and Cyp1b1) in wild-type, AhrKO, and Ahr re-expressed follicles. Further, we compared the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in wild-type, AhrKO, and Ahr re-expressed follicles., Results: Ahr injection into AhrKO follicles partially restored their growth pattern to wild-type levels. Further, Ahr re-expressed follicles had significantly higher levels of Ahr, Ahrr, Cyp1a1, and Cyp1b1 compared to wild-type follicles. Upon TCDD treatment, only Cyp1a1 levels were significantly higher in Ahr re-expressed follicles compared to the levels in wild-type follicles., Conclusion: Our system of re-expression of the Ahr partially restores follicle growth and transcript levels of factors in the AHR signaling pathway to wild-type levels., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Ovarian follicle development is a complex process that begins with the establishment of what is thought to be a finite pool of primordial follicles and culminates in either the atretic degradation of the follicle or the release of a mature oocyte for fertilization. This review highlights the many advances made in understanding these events using transgenic mouse models. Specifically, this review describes the ovarian phenotypes of mice with genetic mutations that affect ovarian differentiation, primordial follicle formation, follicular growth, atresia, ovulation and corpus luteum (CL) formation. In addition, this review describes the phenotypes of mice with mutations in a variety of genes, which affect the hormones that regulate folliculogenesis. Because studies using transgenic animals have revealed a variety of reproductive abnormalities that resemble many reproductive disorders in women, it is likely that studies using transgenic mouse models will impact our understanding of ovarian function and fertility in women.

Objectives: The present study was conducted to assess the associations between a woman's passionate love for her partner and sexual satisfaction and demographic factors, health and life-style characteristics, menopausal status, and menopausal symptoms., Methods: A cross-sectional study was conducted among women (40-60 years) residing in Maryland (n = 846). chi(2)-tests were performed to evaluate the associations between each of the outcome variables (sexual satisfaction and passionate love for the partner) and predictor/independent variables. Logistic regression analysis was performed to determine whether significant associations from chi(2) analyses remained significant after adjustment for confounders., Results: Older age (adjusted odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01, 1.07), higher education (OR 1.47; 95% CI 1.09, 1.99), and alcohol intake (OR 1.42; 95% CI 1.03, 1.95) were associated with low passion for the partner. Older age was also a significant predictor of low sexual satisfaction (OR 1.04; 95% CI 1.01, 1.07). Women experiencing vaginal dryness had higher odds of low passion for partner (OR 1.67; 95% CI 1.21, 1.31) and low sexual satisfaction (OR 1.58; 95% CI 1.14, 2.20) than women not experiencing vaginal dryness., Conclusions: Older age, higher education, alcohol intake, and vaginal dryness are significantly associated with lower levels of passionate love for the partner, while older age and vaginal dryness are significantly associated with lower levels of sexual satisfaction in midlife women.