Ovarian Hormone Levels Research Articles

Modulation of test anxiety-induced salivary protein secretion by ovarian steroid hormones: a preliminary study.

In women the menstrual cycle influences mood and anxiety. Aim of this study was to preliminarily investigate whether different ovarian steroid hormone levels may modulate the psychophysiological responses elicited by test anxiety. Specifically, we compared the secretion of anxiety-induced salivary proteins of healthy women in the early follicular (Pre-Ov group) (low ovarian steroid hormones levels) and mid-luteal (Post-Ov group) (medium/high ovarian steroid hormones levels) phase of the menstrual cycle, during the simulation of an oral examination. Saliva samples were collected before and after a relaxation period and at two post-simulation times and analyzed by two-dimensional electrophoresis and western blot. Proteins corresponding to spots differentially expressed in the two groups across the session were identified through mass spectrometry and most of them corresponded to acute stress and/or oral mucosa immunity biomarkers. The task induced an increase in alpha-amylase, carbonic anhydrase and cystatin S, and a decrease in immunoglobulin light/J chains in both groups. Analogous changes in these proteins have previously been linked to psychological or physical stress. However, specific spots corresponding, for example, to cystatins and 14-3-3 protein, changed exclusively in the Pre-Ov group, while prolactin-inducible protein, polymeric immunoglobulin receptor, fragments of alpha-amylase and immunoglobulins only in the Post-Ov group, indicating a potential modulation of their secretion by ovarian steroid hormones. Overall, the results provide preliminary evidence that ovarian steroid hormones may be a driving factor for differences in physiological responses induced by test anxiety. The results are promising, but further validation in a larger sample is needed.

Daily estradiol and progesterone levels moderate genetic and environmental influences on emotional eating across 45 consecutive days in female twins.

Past studies indicate daily increases in estrogen across the menstrual cycle protect against binge-eating (BE) phenotypes (e.g. emotional eating), whereas increases in progesterone enhance risk. Two previous studies from our laboratory suggest these associations could be due to differential genomic effects of estrogen and progesterone. However, these prior studies were unable to directly model effects of daily changes in hormones on etiologic risk, instead relying on menstrual cycle phase or mean hormone levels. The current study used newly modified twin models to examine, for the first time, the effects of daily changes in estradiol and progesterone on genetic/environmental influences on emotional eating in our archival twin sample assessed across 45 consecutive days. Participants included 468 female twins from the Michigan State University Twin Registry. Daily emotional eating was assessed with the Dutch Eating Behavior Questionnaire, and daily saliva samples were assayed for ovarian hormone levels. Modified genotype × environment interaction models examined daily changes in genetic/environmental effects across hormone levels. Findings revealed differential effects of daily changes in hormones on etiologic risk, with increasing genetic influences across progesterone levels, and increasing shared environmental influences at the highest estradiol levels. Results were consistent across primary analyses examining all study days and sensitivity analyses within menstrual cycle phases. Findings are significant in being the first to identify changes in etiologic risk for BE symptoms across daily hormone levels and highlighting novel mechanisms (e.g. hormone threshold effects, regulation of conserved genes) that may contribute to the etiology of BE.

Efficacy of concurrent utilization of estradiol valerate and Chinese herbal capsule in managing premature ovarian failure.

The objective of this study was to examine the efficacy of the concurrent utilization of estradiol valerate and kuntai capsule (a Chinese herbal preparation) in addressing premature ovarian failure (POF) and its ramifications for ovarian hemodynamics and sex hormone levels. A retrospective study of 104 patients with POF was conducted, dividing them into control (n=50) and observation groups (n=54). The control group received estradiol valerate, while the observation group received estradiol valerate and KunTai capsules over 12 weeks. Clinical effectiveness, ovarian pulsatility index (PI), resistance index (RI), hormone levels, ovarian function, and adverse reactions were analyzed. The observation group showed significantly improved PI, RI, LH, FSH, E2 levels, and ovarian function in relative to the control group (P<0.05). We conclude that the concurrent use of estradiol valerate and KunTai capsules improves ovarian hemodynamics and hormone levels, offering significant clinical benefits.

The therapeutic effects of curcumin on polycystic ovary syndrome by upregulating PPAR-γ expression and reducing oxidative stress in a rat model.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that impacts 8-13% of women in their reproductive years. However, the drugs commonly used to treat PCOS are often prescribed off-label and may carry potential side effects. This study aimed to investigate the therapeutic effects of curcumin in a PCOS rat model. A PCOS rat model was established through daily subcutaneous injection of 60 mg/kg body weight of dehydroepiandrosterone (DHEA) for 21 days. The PCOS rats received a daily intragastric dose of 50 mg/kg body weight of curcumin for another 21 days. Ovarian morphological changes, estrous cycle changes, and hormone level changes were measured to evaluate the therapeutic effectiveness of curcumin in PCOS rats. Oxidative stress markers in the ovaries were analyzed to explore the mechanisms of curcumin in PCOS rats. This study demonstrated that curcumin alleviated insulin resistance and significantly reduced serum levels of estradiol (p = 0.02), luteinizing hormone (p = 0.009), testosterone (p = 0.003), and the LH/FSH ratio (p = 0.008) in PCOS rats. Curcumin also restored normal ovarian morphology and the estrous cycle in these rats. Furthermore, curcumin treatment significantly decreased levels of oxidative stress markers, including malondialdehyde (p = 0.004) and reactive oxygen species (p = 0.005), while increasing antioxidant levels such as superoxide dismutase (p = 0.04), glutathione peroxidase (p = 0.002), and glutathione (p = 0.02) in ovarian tissues. Additionally, curcumin significantly upregulated PPAR-γ in the ovarian tissues of PCOS rats. This study demonstrates that curcumin effectively restores ovarian morphology, hormone levels, and estrous cycles in PCOS rats. These effects may be linked to its ability to reduce oxidative stress in ovaries via the upregulation of PPAR-γ. Curcumin shows promise as a potential drug for the treatment of PCOS.

Effects of sex and estrous cycle on extended-access oxycodone self-administration and cue-induced drug seeking behavior.

Increasing evidence indicates that sex is a factor that impacts the abuse liability and relapse vulnerability of prescription opioids like oxycodone. However, while women are more likely than men to be prescribed and to use these drugs, the impact of sex and ovarian hormones on prescription opioid use and relapse vulnerability remains unclear. Accurately assessing these measures is complicated by the fact that chronic opioid exposure can lower ovarian hormone levels and cause cycle irregularities. Adult male and female Sprague-Dawley rats self-administered oxycodone (0.1 mg/kg/infusion) under extended-access conditions (6 h/day, 10 days) followed by forced abstinence. Separate groups of animals received cue-induced seeking tests in a drug-free state during early (1-2 days) or later periods of abstinence (43-45 days). To track estrous cycle stage, animals were regularly vaginally swabbed throughout the study. We observed oxycodone-induced estrous cycle dysregulation in the majority (~60%) of the animals during both self-administration and the first month of abstinence. In animals whose cycles were not dysregulated, we found a reduction in oxycodone intake during estrus compared to all other cycle stages (non-estrus). We also found that males but not females showed a time-dependent intensification or incubation of cue-induced oxycodone craving over the first 6 weeks of abstinence. This sex difference was estrous cycle-dependent, driven by a selective reduction in drug seeking during estrus. These findings highlight the importance of tracking drug-induced estrous cyclicity and identify a clear impact of ovarian hormones on oxycodone taking and seeking behavior.

Human umbilical cord mesenchymal stem cells restore chemotherapy-induced premature ovarian failure by inhibiting ferroptosis in vitro ovarian culture system

BackgroundMesenchymal stem cells (MSCs) have shown potential in repairing chemotherapy-induced premature ovarian failure (POF). However, challenges such as stem cell loss and immune phagocytosis post-transplantation hinder their application. Due to easy and safe handling, in vitro ovarian culture is widely available for drug screening, pathophysiological research, and in vitro fertilization. MSCs could exhibit therapeutic capacity for ovarian injury, and avoid stem cell loss and immune phagocytosis in vitro tissue culture system. Therefore, this study utilizes an in vitro ovarian culture system to investigate the reparative potential of human umbilical cord mesenchymal stem cells (hUCMSCs) and their mechanism.MethodsIn this study, a chemotherapy-induced POF model was established by introducing cisplatin in vitro ovarian culture system. The reparative effects of hUCMSCs on damaged ovarian tissue were validated through Transwell chambers. Tissue histology examination, immunohistochemical staining, Western blotting, and RT-PCR were employed to evaluate the expression effects of hUCMSCs on ferroptosis and fibrosis-related genes during the process of repairing cisplatin-induced POF.ResultsCisplatin was found to activate ovarian follicles in vitro POF model. Transcriptomic sequencing analysis revealed that cisplatin could activate genes associated with ferroptosis. hUCMSCs alleviated cisplatin-induced POF by suppressing the expression of ferroptosis. Moreover, inhibiting ferroptosis by hUCMSCs also ameliorated ovarian hormone levels and reduced the expression of fibrosis-related factors α-SMA and COL-I in the ovaries.ConclusionsThis study confirms that cisplatin-induced ovarian damage via ferroptosis in vitro POF model, and hUCMSCs repair ovarian injury by inhibiting the ferroptosis pathway and suppressing fibrosis. This research contributes to evaluating the effectiveness of hUCMSCs in treating chemotherapy-induced POF by inhibiting ferroptosis in an in vitro ovarian culture system and provides a potential therapeutic strategy for chemotherapy-induced POF.

Menstrual cycle does not impact the hypoxic ventilatory response and acute mountain sickness prediction

The relationship between the variations in ovarian hormones (i.e., estrogens and progesterone) and the hypoxic ventilatory response (HVR) remains unclear. HVR is a key adaptive mechanism to high altitude and has been proposed as a predictor for acute mountain sickness (AMS). This study aimed to explore the effects of hormonal changes across the menstrual cycle on HVR. Additionally, it assessed the predictive capacity of HVR for AMS and examined whether a particular menstrual phase could enhance its predictive accuracy. Thirteen eumenorrheic women performed a pure nitrogen breathing test near sea level, measuring HVR and cerebral oxygenation in early follicular, late follicular, and mid-luteal phases. Oxidative stress and ovarian hormone levels were also measured. AMS symptoms were evaluated after spending 14 h, including one overnight, at an altitude of 3,375 m. No differences in HVR, ventilation, peripheral oxygen saturation, or cerebral oxygenation were observed between the three menstrual cycle phases. Moreover, these parameters and the oxidative stress markers did not differ between the women with or without AMS (31% vs 69%), regardless of the menstrual cycle phase. In conclusion, ventilatory responses and cerebral oxygenation in normobaric hypoxia were consistent across the menstrual cycle. Furthermore, these parameters did not differentiate women with or without AMS.

8607 Gender Affirming Hormone Therapy: Influence of Brain Network Connectivity Changes on Affect

Abstract Disclosure: J. Andreano: None. A. Lopez: None. M. Misra: None. Background: Previous research indicates that acute gonadal treatments and fluctuations in ovarian hormone levels over the course of the menstrual cycle can alter patterns of communication between brain regions, as well as producing significant changes in self-reported affect. Recent research from our laboratory indicates changes in both brain connectivity and affect with gender affirming hormone therapy (GAHT). However, the relationship between these changes with GAHT are not well understood. Additionally, it is difficult to separate influences of GAHT and transgender identity in understanding differences in connectvity and affect from cisgender controls. A better understanding of the influence of GAHT on intrinsic network connectivity could point the way towards improved GAHT treatment regimens that minimize affective side effects. Objective: To assess relationships between changes in brain network connectivity and affective changes following GAHT, identifying regions in which changes of connectivity are associated with changes in self-reported affect, and to examine differences in brain network connectivity between transgender participants and cisgender controls. Methods: 14 transgender individuals receiving GAHT (estradiol n =7, testosterone n = 7)) were scanned using functional magnetic imaging (fMRI) at rest at two timepoints: baseline, prior to treatment, and 6 months into GAHT. Additionally, 20 cisgender controls (10 male, 10 female) were scanned once each. The time course of neural activity was computed for each voxel in the brain, then tested for correlation with each other voxel to develop a whole-brain connectome for each participant. Maps of average connectivity to two seeds known to associate with two major networks in the brain (posterior cingulate cortex for Default Mode Network, and anterior insula for Salience Network) were then generated for each participant. Within transgender participants, these maps were then compared between the baseline and 6 month timepoints. Additionally, baseline scans were also compared to scans from cisgender controls corresponding to biological sex. Results: Within-subjects analyses of transgender participants showed diverse associations between changes in seed-based connectivity and changes in self-reported anxiety and depression following GAHT in both the default mode and salience networks. Between subjects comparisons showed significantly higher connectivity within the salience network in trans men relative to cis women, as well as greater inter-network connectivity in this group. In contrast, cis men showed greater connectivity within both default mode and salience networks relative to trans women. Conclusions: Changes in affect following GAHT appear related to GAHT-induced changes in network connectivity; these influences appear independent of differences between cis and transgender individuals. Presentation: 6/2/2024

Di-(2-ethylhexyl) phthalate exposure induces ferroptosis by regulating the Nrf2-mediated signaling pathway in mouse ovaries

Di-(2-ethylhexyl) phthalate (DEHP), an endocrine-disrupting chemical present in plasticized products, exerts strong modulation on the anatomy and function of the female reproductive system. However, the potential mechanisms underlying DEHP-induced regulation of prepubertal female reproductive toxicity have not yet been elucidated. Therefore, this study was designed to elucidate the molecular mechanism of ovarian injury induced by DEHP exposure in mice. Elevated serum mono-2-ethylhexyl phthalate (MEHP) concentrations, decreased levels of ovarian hormones (E2 and P4), and observed ovarian injury were found after DEHP exposure. Ovarian transcriptome analysis revealed significant alterations in ferroptosis-associated gene expression, with potential regulation by Nrf2. Subsequent analysis of ferrous iron, malondialdehyde (MDA), Western blotting, and immunofluorescence of the ovaries confirmed the RNA-seq findings. Transcriptome analysis of granulosa cells revealed a direct or indirect regulatory relationship between Nrf2 and downstream ferroptosis-related proteins following MEHP exposure. Further experiments demonstrated that ferrostatin-1 attenuated MEHP-induced ferroptosis in granulosa cells. Additionally, Nrf2 stabilization and accumulation in the nucleus of granulosa cells were observed following MEHP treatment. RNAi-mediated knockdown of Nrf2 exacerbated MEHP-induced ferroptosis in granulosa cells. This evidence indicates that DEHP exposure induces ferroptosis through regulation of the Nrf2-mediated signaling pathway in mouse ovaries, laying the groundwork for future studies aiming to develop therapeutic strategies against DEHP toxicity.

Metabolomic and Transcriptomic Analyses Reveal the Potential Mechanisms of Dynamic Ovarian Development in Goats during Sexual Maturation.

The ovary is a crucial reproductive organ in mammals, and its development directly influences an individual's sexual maturity and reproductive capacity. To comprehensively describe ovarian sexual maturation in goats, we integrated phenotypic, hormonal, metabolomic, and transcriptomic data from four specific time points: after birth (D1), at 2 months old (M2), at 4 months old (M4), and at 6 month old (M6). The study showed that during the early stage (D1-M2), ovarian growth was the most rapid, with weight and morphology increasing by 284% and 65%, respectively, and hormone levels rose significantly, with estradiol increasing by 57%. Metabolomic analysis identified 1231 metabolites, primarily lipids, lipid molecules, and organic acids, which can support hormone balance and follicle development by providing energy and participating in signaling transduction. Transcriptomic analysis identified 543 stage-specific differentially expressed genes, mainly enriched in steroid biosynthesis, amino acid metabolism, and the PI3K/AKT pathway, which are key factors influencing ovarian cell proliferation, apoptosis, hormone secretion, and metabolism. The integrated analysis revealed the key processes in the ovarian steroid hormone biosynthesis pathway and gene/metabolite networks associated with ovarian phenotypes and hormone levels, ultimately highlighting scavenger receptor class B type 1 (SCARB1), Cytochrome P450 Family 1 Subfamily A Member 1 (CYP11A1), 3beta-hydroxysteroid dehydrogenase (3BHSD), progesterone, estradiol, and L-phenylalanine as key regulators of ovarian morphological and functional changes at different developmental stages. This study is the first to reveal the metabolic changes and molecular regulatory mechanisms during ovarian sexual maturation in goats, providing valuable insights for understanding reproductive system development and optimizing reproductive performance and breeding efficiency.

Effect of early postmenopause and premenopause on resting-state electroencephalographic and their correlation with ovarian hormone levels.

This study aimed to compare the effect of the early postmenopausal period on resting-state electroencephalographic spectral power with that of the premenopausal period and to analyze the correlation between electroencephalographic spectral power values and endogenous ovarian hormone levels. This study involved 13 early postmenopausal women and 10 premenopausal women in the early follicular, 10 in the ovulatory phase, and 10 in the early luteal phase who underwent resting-state quantitative electroencephalographic spectral power with eyes closed and endogenous ovarian hormone measurements. The delta, theta, alpha1, alpha2, beta1, and beta2 absolute power were compared between the early postmenopausal and premenopausal groups. Correlations between electroencephalographic spectral power values and 17β estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone levels were analyzed in early postmenopausal women. Compared with the premenopausal group, the early postmenopausal group showed significantly higher resting-state theta power in the frontal region, alpha1 and alpha2 power in the frontal and central regions, beta1 power in the frontal, central, parietal, and occipital regions, and beta2 power in the centroparietal region. Beta2 power values were positively correlated with FSH levels. The current findings highlight that early postmenopausal women show greater resting-state alpha and beta power, which suggests cortical excitability of fast frequency bands involved in states of alertness, focus of attention, cognition, and emotion. Additionally, we emphasized the effect of FSH levels on fast cortical activation in early postmenopausal women.

Complex ontogeny of sexual size dimorphism in a female-larger gecko: Implications of determinate growth for lizard body size and life-history evolution.

Ectothermic vertebrates such as reptiles were assumed to be indeterminate growers, which means that there is no terminal point in time or size for growth in their lifetime. In recent years, evidence for the determinate nature of growth in lizards has accumulated, necessitating a re-examination of models of their ontogeny and evolution of sexual size dimorphism (SSD). In the female-larger gecko Paroedura vazimba, we monitored post-embryonic growth over a period of 15 months. After hatching, females grew faster than males but also reached their final body size, that is, closed growth of their vertebrae, earlier than males. The closure of bone growth in females correlates with the onset of reproductive maturation. We compared this pattern with the previously minutely studied, male-larger species Paroedura picta, where we documented determinate growth as well. We propose a model to explain the evolutionary switches in the direction of SSD in lizards based on bipotential effects of ovarian hormones on growth. In this model, male growth is assumed to require no male-specific growth modifier, such as sex-limited hormonal regulators, while growth is feminized by ovarian hormones in females. Low levels of ovarian hormones can promote bone growth, but high levels associated with maturation of the reproductive organs promote senescence of bone growth plates and thus cessation of bone growth. We suggest that models on growth, life-history and evolution of body size in many lizards should acknowledge their determinate nature of growth.

Combined perceptual and chemical analyses show no compelling evidence for ovulatory cycle shifts in women's axillary odour.

Although men's attraction to women's body odour has been suggested to vary over the ovulatory cycle, peaking around the fertile window, we still lack methodologically robust evidence corroborating this effect. Further, the chemical underpinnings of male preference for the odour of ovulating women remain unknown. Here, we combined perceptual and chemical analyses to investigate the axillary odour of naturally cycling women over 10 days, covering the gradual change in fertility across the ovulatory cycle with a focus on fertile days. The fertile state was confirmed by urinary ovulation tests as well as salivary oestradiol and progesterone levels. Men rated the scent of unfamiliar women, resembling a first encounter. We used multivariate analyses to relate variation in both odour ratings and chemical composition to female conception probability, temporal distance to ovulation and ovarian hormone levels. Our results provide no evidence that males prefer the odour of fertile women. Furthermore, the volatile analysis indicated no link between axillary odour composition and current fertility status. Together, our results showed no convincing support for a chemical fertility cue in women's axillary odour, questioning the presence of olfactory fertility information that is recognizable during first encounters in modern humans.

P-793 New approaches for treating diminished ovarian reserve: MSC-derived extracellular vesicles and autologous platelet rich plasma

Abstract Study question Does intraovarian injection of MSC-Derived Extracellular Vesicles (EVs) and autologous platelet rich plasma (PRP) improves the outcome of IVF in women with Diminished Ovarian reserve? Summary answer EVs and PRP therapies increse Antral follicle count (AFC), lower FSH level and result in higher amount of mature oocytes and blastocysts What is known already Diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) are significant impediments to the success of in vitro fertilization (IVF). Current strategies for ovarian stimulation primarily affects only the growth of antral follicles. Even in scenarios where ovarian ovulatory function is compromised, a reservoir of dormant follicles persists, which could potentially be activated by stem cells. Mesenchymal stem cells (MSCs), owing to their multipotent differentiation capabilities and paracrine signaling properties, have emerged as leading candidates for innovative therapeutic approaches. Recent scientific inquiries have highlighted the paracrine impact of EVs secreted by stem cells, underscoring their prospective therapeutic relevance. Study design, size, duration This prospective interventional study was conducted at the V.I. Kulakov Scientific Research Center for Obstetrics, Gynecology, and Perinatology in Russia. It involved 60 infertile female participants aged 20 to 38 years, each with DOR and a history of at least two unsuccessful IVF cycles. These participants were enrolled in the study during their subsequent IVF cycle. Prior to inclusion, all patients provided written informed consent. Participants/materials, setting, methods Patients in group 1 (n = 30) received treatment with exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs-Exos) prior to initiating their in vitro fertilization (IVF) cycle. In contrast, participants in group 2 (n = 30) underwent intraovarian therapy with autologous platelet-rich plasma (PRP) in preparation for their IVF cycle. The comparative analysis encompassed antral follicle count (AFC), anti-Müllerian hormone (AMH) levels, follicle-stimulating hormone (FSH) levels, ovarian stimulation outcomes, and the primary characteristics of oogenesis and embryogenesis. Main results and the role of chance After transplantation of EVs and PRP the ovarian function-related hormone levels and the AFC returned to nearly normal parameteres.Meanwhile, after exosomal treatment the improvement in reproductive outcomes was more significant. FSH concentration was significantly different before and 30 days after the procedure in both groups. In group 1 FSH values were less than the initial data In 95% of cases, in group 2 – in 72% of cases. AMH levels did not change significantly in both groups. The AFC increased in group 1 compared to group 2. All Patients underwent an IVF antagonist cycle after 3 months from the treatment. The number of obtained oocytes in group 1 ranged from 2 to 8, MII from 1 to 6; in group 2: from 0-5, MII – 0-5. The number of blastocysts in group 1 ranged from 1 to 5, in group 2 – from 0 to 3. In group 1, pregnancy occurred in 9 patients (30%): 1 women ( 3,3%) conceived spontaneously in the cycle of procedures, 8 (26,7%) attempted IVF, in group 2 pregnancy occurred in 4 patients (13,3%): 4 attempted IVF. EVs and PRP injections improve outcomes of IVF results in women with low ovarian reserve. Limitations, reasons for caution Limitations may include the fact that the study is single-center and has a rather small amount of patients enrolled in the study. Fundamental approaches to further research in this area are also required to better understand the obtained results. Wider implications of the findings EVs and PRP therapies appear to enhance ovarian reserve metrics and the success rates of IVF programs in patients with DOR. The clinical implementation of these interventions may offer improved reproductive prospects for patients whose sole option was previously oocyte donation. Trial registration number 121040600410-7

Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage.

Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy. This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy. A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included 'ovarian microenvironment' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine). The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors. Ovarian function is determined by its 'seeds' (follicles) and 'soil' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field. Not applicable.

The Effects of Saturated and Polyunsaturated Fatty Acids on Reproductive Performance and Reproductive Hormonal Changes in Dairy Cows at the Transition Period

Reproductive success is crucial in dairy farming as it heavily relies on the consumption of a complete mixed ration for the diet. The current study investigated the effects of adding saturated (SFA) and polyunsaturated fatty acids (PUFAs) to dairy cows' diets on reproductive performance and reproductive hormones during the transition period. A total of 30 Holstein dairy cows were randomly divided into three groups (10 animals in each group), based on parity and body condition score. The cows had an initial body weight of 567.5 ± 40.3 kg (mean ± SD), a body condition score of 3.5 ± 0.26 out of 5 (mean ± SD), and a parity of 1.7 ± 0.02 (mean ± SD). The control group received a balanced ration meeting all the nutrient requirements according to the National Research Council (NRC) guidelines. The SFA group received 1.4% of dry matter (DM) as palm oil (RumiFat®), while the omega group had 5% of DM as safflower (a source of n-6 fatty acids) added from 21 days before parturition to 21 days after, and 4% of DM as flaxseed (a source of n-3 fatty acids) added from 21 to 42 days after parturition. In the Omega group, estradiol concentration significantly increased on artificial insemination (AI) day (12.54 pg/mL). Additionally, serum prostaglandin F2-alpha concentration was significantly higher in the omega group (0.732 pg/mL on day 7 and 1.68 pg/mL on day 14) compared to other groups. The control group exhibited the highest progesterone concentrations at 14 and 21 days post-calving compared to the other groups, other groups. whereas the omega group highest concentration five days after AI. The omega group also showed a significantly higher mean number of follicles &gt;10mm and larger ovulatory follicle diameter. Moreover, a higher percentage of pregnant cows at 120 days in milk, fewer open days, and lower service per conception were observed in the omega group compared to the other groups. In conclusion, supplementing dairy cows' diets with PUFAs during the transition period positively influenced ovarian function, hormone levels, and reproductive performance.

Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation

BackgroundThyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid‐treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known.AimsTo determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes.Materials and MethodsProspective cohort study involving 46 euthyroid (anti‐thyroid peroxidase antibody negative) and 16 levothyroxine‐replaced women with baseline thyroid‐stimulating hormone (TSH) &lt;2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick‐up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared.ResultsMedian serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine‐replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine‐replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ.ConclusionAdequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Impact of repeated ovarian hyperstimulation on the reproductive function

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Struma Ovarii during Pregnancy.

Struma ovarii is a rare type of ovarian teratoma primarily composed of over 50% thyroid tissue. Its occurrence is reported in 2-5% of all ovarian teratomas, with approximately 0.5% to 10% showing malignant transformation. Managing it during pregnancy poses significant challenges as pregnancy can promote the growth of malignant struma ovarii due to elevated levels of ovarian and pregnancy-related hormones, including estrogen, progesterone, and human chorionic gonadotrophin (hCG). Most ovarian tumors, including struma ovarii, are detected during routine ultrasonography in the first and second trimesters, often as acute emergencies. Diagnosis during pregnancy is rare, with some cases incidentally discovered during cesarean section when inspecting the adnexa for ovarian cysts. This review explores the diagnostic, management, and therapeutic approaches to struma ovarii during pregnancy.

Regulation of mitochondrial dysfunction by estrogens and estrogen receptors in Alzheimer's disease: A focused review.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily manifests itself by progressive memory loss and cognitive decline, thus significantly affecting memory functions and quality of life. In this review, we proceed from the understanding that the canonical amyloid-β hypothesis, while significant, has faced setbacks, highlighting the need to adopt a broader perspective considering the intricate interplay of diverse pathological pathways for effective AD treatments. Sex differences in AD offer valuable insights into a better understanding of its pathophysiology. Fluctuation of the levels of ovarian sex hormones during perimenopause is associated with changes in glucose metabolism, as a possible window of opportunity to further understand the roles of sex steroid hormones and their associated receptors in the pathophysiology of AD. We review these dimensions, emphasizing the potential of estrogen receptors (ERs) to reveal mitochondrial functions in the search for further research and therapeutic strategies for AD pharmacotherapy. Understanding and addressing the intricate interactions of mitochondrial dysfunction and ERs potentially pave the way for more effective approaches to AD therapy.