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Study Question: Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)?Summary Answer: We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors.What Is Known Already: Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown.Study Design, Size, Duration: A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants.Participants/materials, Setting, Methods: AYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry.Main Results and the Role Of Chance: The median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures.Limitations, Reasons For Caution: Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress.Wider Implications Of the Findings: The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans.Study Funding/competing Interest(s): NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Problem Tumor necrosis factor-like weak inducer of apoptosis ( TWEAK)/fibroblast growth factor-inducible 14 (Fn14) interactions affect the regulation of cytotoxic/immunotrophic pathways that are themselves under control of IL-18. The effect of Fn14 on regulation of endometrium IL-18 expression, however, remains unclear. Method and study The aim was to determine the mode of ovarian steroid action in regulating Fn14 expression by goat endometrial epithelial cells ( EECs) in the presence and absence of endometrial stromal cells ( ESCs). The possible role of Fn14 on the expression of IL-18 by EECs was also evaluated. Results Opposite effects of E2 and/or P4 on the regulation of both Fn14 mRNA and protein expression by EECs were observed in the presence and absence of ESCs. Fn14 knockdown by blocking antibody or siRNA resulted in a decrease of IL-18 mRNA and protein levels in EECs cocultured with ESCs, and no significant difference of the IL-18 mRNA and protein levels in the EECs was observed between steroid treatment group and control group. Conclusion These findings confirm the importance of steroids in controlling Fn14 expression in goat EECs. Furthermore, Fn14 appears as a novel modulator of the steroid-related IL-18 expression in EECs in the presence of ESCs. [ABSTRACT FROM AUTHOR]

Abstract: Assisted reproductive techniques, such as ovarian manipulation and artificial insemination, are useful for enhancing genetic management of threatened wildlife maintained ex situ. In this study, we used noninvasive fecal hormone monitoring to investigate (1) the influence of pairing with a male on endocrine responses of female maned wolves (Chrysocyon brachyurus) to a GnRH agonist (deslorelin) and (2) the efficiency of recombinant LH (reLH) on ovulation induction in females housed alone. Deslorelin (2.1 mg Ovuplant) was given to females that were either paired with a male (n = 4) or housed alone (n = 7); the implant was removed 7 to 11 days postimplantation. Three of seven singleton females were injected with reLH (0.0375 mg) on the day of implant removal, whereas the remaining females (n = 4) did not receive the additional treatment. Fecal samples were collected 5 to 7 days/wk from all females starting 11 days prior to hormone insertion until at least 70 days post implant removal for a total of 11 hormone treatment cycles. Fecal estrogen and progestagen metabolites were extracted and analyzed by enzyme immunoassay. Evidence of ovulation, demonstrated by a surge of estrogen followed by a significant rise in progestagen, occurred in all paired females. Three of the four singleton females that did not receive reLH treatment exhibited no rise in progestagen after an estrogen surge. All singleton females treated with reLH exhibited a rise in fecal progestagen after injection, indicating ovulation. In conclusion, deslorelin is effective at inducing ovarian activity and ovulation in paired female maned wolves; however, exogenous reLH is needed to induce ovulation in females housed alone. The findings obtained from this study serve as a foundation for future application of artificial insemination to enhance genetic management of this threatened species ex situ. [Copyright &y& Elsevier]

Abstract: A primary role of epithelial-stromal interactions in mediating steroid hormone action in the uterus has been established. The present study was undertaken to determine the mode of ovarian steroid action in regulating IL-18 release by goat endometrial epithelial cells (EECs) in the presence and absence of endometrial stromal cells (ESCs). Primary and telomerase-immortalized goat EECs grown alone or cocultured with ESCs were treated with two ovarian steroids, 17β-estradiol (E2) and progesterone (P4). The IL-18 mRNA and protein expression in EECs were studied by reverse transcript (RT) PCR, ELISA, and Western blot assay. The E2 and/or P4 treatment of EECs led to a significant increase in both IL-18 mRNA and protein expression either in the primary or in the immortalized EECs compared with that in EECs without the steroid treatment. However, in the presence of ESCs, IL-18 expression by EECs treated with steroids was significantly decreased compared with cells untreated with E2 and/or P4. In addition, significantly high abundance of IL-18 mRNA and protein expression by primary and telomerase-immortalized goat EECs was observed in the presence of ESCs compared with those cells without ESCs. These findings suggest that steroids are important for the control of IL-18 expression in goat EECs. Underlying ESCs are needed to mediate the inhibitory effects of steroids on the IL-18 secretory activity of goat EECs in vitro. The IL-18 abundance expressed by goat EECs in vitro are enhanced by underlying ESCs without the treatment of E2 and/or P4. [Copyright &y& Elsevier]

Abstract: Food intake is decreased during the late follicular phase and increased in the luteal phase of the menstrual cycle. While a changing ovarian steroid milieu is believed to be responsible for this behavior, the specific mechanisms involved are poorly understood. Brain activity in response to visual food stimuli was compared during the estrogen dominant peri-ovulatory phase and the progesterone dominant luteal phase of the menstrual cycle. Twelve women underwent functional magnetic resonance imaging during the peri-ovulatory and luteal phases of the menstrual cycle in a counterbalanced fashion. Whole brain T2* images were collected while subjects viewed pictures of high calorie (HC) foods, low calorie (LC) foods, and control (C) pictures presented in a block design. Blood oxygen level dependent (BOLD) signal in the late follicular phase and luteal phase was determined for the contrasts HC–C, LC–C, HC–LC, and LC–HC. Both HC and LC stimuli activated numerous corticolimbic brain regions in the follicular phase, whereas only HC stimuli were effective in the luteal phase. Activation of the nucleus accumbens (NAc), amygdala, and hippocampus in response to the HC–C contrast and the hippocampus in response to the LC–C contrast was significantly increased in the late follicular phase compared to the luteal phase. Activation of the orbitofrontal cortex and mid cingulum in response to the HC–LC contrast was greater during the luteal phase. These results demonstrate for the first time that brain responses to visual food cues are influenced by menstrual cycle phase. We postulate that ovarian steroid modulation of the corticolimbic brain contributes to changes in ingestive behavior during the menstrual cycle. [Copyright &y& Elsevier]

Abstract: Peptide YY (PYY) is produced in L cells of the intestine and is released after eating. PYY circulates in a truncated form designated PYY3–36. PYY3–36 is thought to be a physiologic anorexigenic peptide. The objective of the current study was to test the effect of exogenous PYY3–36 on food intake in non-human primates exposed to different ovarian steroid milieus. The study was conducted in four ovariectomized cynomolgus monkeys replaced with estrogen alone for 2 weeks followed by estrogen in combination with progesterone for 2 weeks to mimic the menstrual cycle. The effect of PYY3–36 on food intake was tested during each week of the simulated menstrual cycle by comparing the 2 h food intake following intracerebroventricular (icv) injection of artificial cerebrospinal fluid (aCSF) or PYY3–36. Despite considerable variation in food intake following aCSF, PYY3–36 consistently inhibited food consumption, except during week 2 of estrogen plus progesterone replacement. PYY3–36 reduced food consumption by 16.2 g (95% confidence interval (CI)=4.5–27.9 g) and 26.6 g (95% CI=7.3–45.9 g) in weeks 1 and 2 respectively of estrogen only treatment and by 38.2 g (95% CI=26.1–50.2 g) in week 1 of estrogen plus progesterone treatment. In contrast, PYY3–36 injected in week 2 of estrogen plus progesterone did not consistently inhibit food intake (13.1 g; CI=−49.5–75.7). This is the first study to report the effect of PYY3–36 on food consumption in female monkeys. We conclude that icv administration of PYY3–36 has a strong anorexic effect in female cynomolgus monkeys and that sensitivity to PYY3–36 may be influenced by the ovarian steroid milieu. [Copyright &y& Elsevier]