Aging attenuates the ovarian circadian rhythm

ObjectiveTo study the effect of aging on ovarian circadian rhythm.DesignHuman and animal study.SettingUniversity hospital and research laboratory.Patients/animalsHuman granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice.Intervention(s)None.Main outcome measure(s)Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice.Result(s)All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice.Conclusion(s)Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01943-y) contains supplementary material, which is available to authorized users.     

Serous ovarian tumors: Immunohistochemical profiling as an aid to grading and understanding tumorigenesis

BackgroundThe aim of this study was to evaluate the expression of p53, p16, Wilms tumor gene (WT1), and Mindbomb E3 Ubiquitin Protein Ligase 1 (MIB-1) index by immunohistochemical (IHC) staining in benign, low-grade, and high-grade serous ovarian tumors.MethodsForty-one cases of ovarian serous tumors were included in the study (benign serous tumor [n = 10], low-grade ovarian serous carcinoma [n = 8], and high-grade ovarian serous carcinoma [n = 23]). Expression of p53, p16, WT1, and MIB-1 by IHC was evaluated statistically with the grade of tumor. Semiquantitative scoring system for percentage (0–5) and intensity (1–3) of staining pattern was used to bring about objectivity.Resultsp53, p16, and WT1 showed significantly higher staining scores in ovarian serous carcinoma group than in the benign group (p < 0.05). However, p16 score was not significant in benign versus low-grade tumors. In the carcinoma group, the high-grade serous tumors showed significantly higher staining scores of p53, p16, and WT1 than the low-grade serous tumors (p < 0.05). Papillary serous tumors had comparatively lower p53 and WT1 scores for the same grade of tumor. MIB-1 scores were not significant.Conclusionp53, p16, and WT1 are helpful for the subtyping of serous ovarian tumors as low grade and high grade. WT1 is helpful in establishing primary ovarian serous tumors. The combination of moderate-to-high p53 and WT1 scores provides a robust way of confirming high-grade tumors.     

Ovarian and peritoneal psammocarcinoma: Results of a multicenter study on 25 patients

PurposePsammocarcinoma (PK) is a rare disease of unknown origin. We aimed to report the characteristics, management and survival of patients operated on for PK within the French Network for Rare Peritoneal Malignancies (RENAPE) expert centers.Patients and methodsAll consecutive cases of PK operated within all 26 RENAPE centers between 1997 and 2018 were retrospectively analyzed.ResultsTwenty-five patients were identified. The median age was 53 years [range 17–78]. None of the patients had extra peritoneal metastases at diagnosis. A median of 6 cycles of carboplatin-based systemic chemotherapy was delivered in 52% preoperatively (n = 13) and 56% postoperatively (n = 14); associated with placlitaxel for 12 patients. All patients were operated on. The median PCI was 23 [0–33]. Eighty-four percent had a complete cytoreductive surgery through digestive (n = 7), spleen (n = 3), pancreas (n = 1) resections and/or multiple peritonectomies (n = 11). Five patients (20%) had intraperitoneal chemotherapy. Morbidity (Dindo-Clavien ≥3) was 12%. No postoperative death occurred. After a median follow-up of 42 months (range [2–194]), the median overall (OS) and progression-free (DFS) survival times were respectively 128 months and 31 months. Eighteen patients recurred (72%), mainly in the peritoneum (n = 16). Four of them (22%) were reoperated. The 5 and 10-year DFS rates were both 20.3%. The 5 and 10-year OS rates were 62% and 51.7%, respectively. A complete cytoreductive surgery was associated with a better OS and DFS in a univariate analysis.ConclusionComplete cytoreductive surgery is the cornerstone of the PK's management as a primary treatment. Recurrence remains common and new adjuvant strategies seem needed.     

Redox imbalance in age-related ovarian dysfunction and perspectives for its prevention

The age at which women have their first child is increasing. This change represents a major health problem to society because advanced maternal age is related with a decay in fertility and an increase in the incidence of a variety of pregnancy complications and offspring health issues. The ovary stands as the main contributor for female reproductive ageing because of the progressive age-related decrease in follicle number and oocyte quality. Loss of redox homeostasis and establishment of an ovarian oxidative microenvironment are seen as major underlying causes for such downfall and impairment of ovarian function. Thus, the use of antioxidants to preserve fertility became an important field of research. In this review, new insights on mechanisms underlying the establishment of oxidative stress and its repercussions on ovarian ageing are addressed, along with the current state of knowledge on antioxidant supplementation and its contribution for healthy ageing and extension of ovarian lifespan.     

The role of ultrasound in the study of polycystic ovarian disease

Seventy-eight patients with clinical findings pointing to possible polycystic ovarian disease (POD) were studied by ultrasound examination. The endocrine status of each patient was evaluated by assay of blood progesterone levels and gonadotropin luteinizing hormone and follicle-stimulating hormone (LH-FSH), both under basal conditions and after luteinizing hormone releasing factor (LH-RH) and androgen hormone stimulation (testosterone and 17-ketosteroids under basal conditions and after a suppression test with dexamethasone). POD was diagnosed in nine cases and confirmed in four at operation. Ultrasound examination as an aid to POD diagnosis is discussed and its value underlined as a precise method in determining ovarian size, shape, and structure, and as a follow-up for patients after surgery.     

Struma ovarii: CT findings

Background  The purpose of this study was to evaluate computed tomographic findings of struma ovarii. Methods  Computed tomography (CT) scans of 13 pathologically proven struma ovarii were retrospectively reviewed by two radiologists in consensus. Scans were evaluated for the laterality, size, mass configuration, margins, internal architecture, presence of intracystic high attenuation lesions on precontrast scans, and cyst wall enhancement. Results  The mean size of the tumors was 11.4 cm (range 4.7–21.0 cm). Mainly cystic (n = 8, 61.5%) or cystic (n = 5, 38.5%) appearance was common to all the tumors. All tumors were unilateral and had smooth margins. The most common internal architecture in the tumors was multicystic architecture (n = 11, 84.6%). Eleven tumors (84.6%) showed a high attenuation lesion in the cyst portion of the mass on precontrast scans and the attenuation ranged from 92.2 to 120.5 Hounsfield units (HU) (mean, 106.8 ± 8.8 HU). The cyst wall showed no (n = 7, 53.8%), moderate (n = 5, 38.5%), or marked (n = 1, 7.7%) enhancement after administration of contrast medium. Conclusions  On CT scans, struma ovarii appeared most often as a smooth marginated multicystic mass with a high attenuation lesion on precontrast scans and no or moderate cyst wall enhancement.     

In utero exposure to the endocrine disruptor di(2-ethylhexyl) phthalate targets ovarian theca cells and steroidogenesis in the adult female rat

Di-2-ethylhexyl phthalate (DEHP) is an endocrine disruptor used in industry as an additive to polyvinyl chloride-based products. Pregnant dams were gavaged with oil, 1, 20, 50, or 300 mg of DEHP/kg/day from gestational day 14 until birth in order to characterize the effects of DEHP in the adult female offspring. In utero exposure to DEHP resulted in reduced estrogen levels at proestrus. Theca cell layer thickness was decreased starting at 50 mg DEHP/kg/day dose. Follicle-stimulating hormone levels were significantly increased at proestrus and estrus. F1 reproduction using a known breeder was not affected. F3 generation showed a decreased pregnancy rate and weight, and increased litter size in the animals exposed to 20 mg DEHP/kg/day. The data presented herein suggest that in utero exposure to DEHP targets the theca cell layer and decreases the estrus cycle steroid surge, but despite these effects, does not cause infertility.