Early Luteal Research Articles

Monitoring Contractility of Junctional Zone Endometrium across Menstrual Cycle Using the ElectroUteroGraph (EUG): A Clinical Evaluation

(1) Background: Abnormal uterine contractility for nonpregnant women has been associated with gynecological pathologies and infertility. The objective of this study was to evaluate the ability of a novel monitoring technique to assess the contractility of the nongravid uterus using a simple, standardized, direct, in vivo methodology during the different phases of the menstrual cycle. (2) Methods: Twenty-six healthy women of reproductive age (28–48 years) were recruited. An ElectroUteroGraph (EUG) was used to measure the electrical activity from the contractility of the junctional zone endometrium (JZE) across the menstrual cycle. Derived recordings were separated into the early proliferative (EP) (n = 10), late proliferative (LP) (n = 31), early luteal (EL) (n = 27), and late luteal (LL) (n = 12) phases of the menstrual cycle. EUG recordings were performed by inserting a flexible electrode array into the endometrial cavity. (3) Results: Waveforms that were measured from the electrode closer to the fundus (1 cm distance) were processed. The Root-Mean-Square (RMS) Voltage Amplitude (VJZE-RMS) (in μV) and the Mean Frequency (fJZE-mean) (in cycles/min) of the JZE’s electrical activity, as direct indicators of the intensity and frequency changes in the JZE’s contractions, were extracted from the recorded waveforms. There was a trend in the median values of the VJZE-RMS decreasing from the EP to the LP phase (247–158 μV). During the EL phase, an upward trend was observed (158–374 μV, p < 0.05), reaching its highest value during the LL phase (374–477 μV, p < 0.05) when compared to the LP phase. The fJZE-mean showed the opposite trend, increasing from 2.5 cycles/min during the EP phase to 2.96 cycles/min during the LP phase. During the EL phase, a downward trend was observed (2.96–2.37 cycles/min), continuing to fall to 1.33 cycles/min, in the LL phase, with p < 0.05 when compared to the previous three phases. (4) Conclusions: The novel in vivo monitoring technique has shown clinically, for the first time, significant electrical activity differences in the different sub-phases of the menstrual cycle, recorded in a safe and painless way.

Attention, response inhibition, impulsivity, and decision-making within luteal phase in women with premenstrual dysphoric disorder.

Cognitive impairment is a key feature of depressive disorder. Various forms of cognitive function have yet to be investigated in women with premenstrual dysphoric disorder (PMDD) during early luteal (EL) and late luteal (LL) phases. Therefore, we evaluated response inhibition and attention in PMDD in these two phases. We also examined the associations between cognitive functions, impulsivity, decision-making style, and irritability. There is a total of 63 female participants with PMDD and 53 controls, as determined through psychiatric diagnostic interviewing and a weekly symptoms checklist. The participants completed a Go/No-go task, Dickman's impulsivity inventory, Preference for Intuition and Deliberation scale, and the Buss-Durkee Hostility Inventory: Chinese Version-Short Form at the EL and LL phases. The women with PMDD had poorer attention in the Go trials at the LL phase and poorer response inhibition in the No-go trials at the EL and LL phases. Repeated measures analysis of variance revealed an LL exacerbation of deficit in attention among PMDD group. In addition, impulsivity negatively correlated with response inhibition at the LL phase. Preference for deliberation correlated with attention at the LL phase. Women with PMDD experienced LL declined attention and impaired response inhibition across the luteal phase. Response inhibition is linked to impulsivity. The deficit in attention links preference for deliberation among women with PMDD. These results reveal the different courses in different domains of cognitive impairment in PMDD. Further studies are required to elucidate the mechanism underlying cognitive dysfunction in PMDD.

Early and Late Luteal Executive Function, Cognitive and Somatic Symptoms, and Emotional Regulation of Women with Premenstrual Dysphoric Disorder.

Objective: Cognitive and somatic symptoms were vital factors in developing personalized treatment of depressive disorder. The study aimed to evaluate the following: (1) the cognitive and somatic symptoms of premenstrual dysphoric disorder (PMDD) in the early luteal (EL) and later luteal (LL) phase; and (2) their association with depression and functional impairment of PMDD. Methods: We prospectively evaluated executive function, emotion regulation, cognitive and somatic symptoms, and depression in the EL and LL phases in women with PMDD. Sixty-three women with PMDD and 53 healthy controls completed Simon’s task and questionnaire to assess emotion regulation, inattention, fatigue, insomnia, and depression. Results: Women with PMDD had a poor performance in Simon’s task during the LL phase. They were less likely to exercise cognitive reappraisal during EL and LL phases. Their cognitive reappraisal positively correlated with executive function and negatively associated with depression. In the LL phase, they also experience higher inattention, insomnia, and fatigue, which correlate with the depression and functional impairment of PMDD. Inattention is the most associated factor of PMDD and functional impairment in controlling depression. Conclusion: Executive function was impaired in women with PMDD during the LL phase. Its performance correlated positively with emotion regulation and negatively with depression. The association between inattention and PMDD functional impairment indicates that evaluation and intervention for cognitive impairment were essential in treating women with PMDD. Further studies were required to elucidate the possible etiology underlying these associations.

Relative expression profile of Kisspeptin (Kiss1-Kiss1r) and gonadotrophin receptor in the ovarian follicular tissue and their association in the Buffalo (Bubalus bubalis)

In the past decade, kisspeptin research was primarily focussed on the regulation of GnRH release in hypothalamus. Present study was designed to explore the expression of extra-hypothalamic kisspeptinergic (Kiss1- Kiss1r) system in the follicular compartment of buffalo ovary. Buffalo genitalia (n=32) were collected immediately after exsanguinations and categorized into early luteal (EL), mid luteal (ML), follicular (FL) and acyclic (n=8 per group), based on the gross ovarian morphology. Ovarian follicular tissue samples were subjected to total RNA extraction, cDNA synthesis and qPCR amplification of Kiss1, Kiss1r, follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) along with an endogenous control (β-actin) gene. The expression of ovarian Kiss1 transcripts was abundant in the cyclic than acyclic stage. The fold change was significantly upregulated in ML (66.79 fold) followed by EL (28.64 fold) and FL (14.09 fold) stages against the acyclic stage (calibrator). Similarly, the Kiss1r expression was highest at ML (77.26 fold). The expression of FSHR was upregulated at FL (15.08 fold) stage in response to follicular activity and subsequently observed to be down regulated at EL (0.09 times) and ML (0.27 times). Further, the expression of Kiss1 was positively correlated with FSHR only at ML and FL. From this study, it could be concluded that Kiss1 and Kiss1r are expressed in the buffalo ovarian follicle and their expression is associated with the stage of estrous cycle.

Natural Fluctuations in Progesterone Do Not Impact Vascular Function in Healthy Premenopausal Women

Endogenous sex hormone concentrations vary across the menstrual cycle of naturally menstruating premenopausal women and may elicit concomitant changes in vascular function. Specifically, estrogen (E2) may enhance vascular function, partially by increasing nitric oxide bioavailability. In contrast, the influence of progesterone (P4) on vascular function remains unclear, with some data suggesting it increases nitric oxide bioavailability and other data suggesting it antagonizes the dilatory effects of E2. The objective of the study was to elucidate potential effects of P4 on the macrovascular function of healthy premenopausal women in the presence of relatively lower E2 concentrations. It was hypothesized that measures of macrovascular function would be similar between the early follicular (EF) and early luteal (EL) phases of healthy premenopausal women, despite a significant increase in the progesterone-to-estrogen ratio from the EF to the EL phase. Sex hormones and vascular function were measured in ten healthy premenopausal women (22±2 y) during the EF phase (within 5 days of the onset of menstruation) and the EL phase (4±2 days post-ovulation) of a single menstrual cycle. Serum concentrations of E2 and P4 were analyzed using enzyme-linked immunosorbent assays. Independent concentrations of E2 and P4 were calculated, as well as P4:E2. Macrovascular function was assessed via brachial artery flow-mediated dilation (FMD). %FMD was calculated as the percent change in brachial artery diameter following an ischemic stimulus. Data were compared between phases with paired t-tests. Serum concentrations of E2 and P4 increased from the EF to the EL phase (91.8±34.5 vs. 120.9±32.6 pg/mL, p=0.01 and 1.4±0.6 vs. 5.1±3.6 ng/mL, p=0.01, respectively). The P4:E2 increased significantly from the EF to the EL phase as a result of the P4 surge in the EL phase (15.5±4.8 vs. 42.9±30.5, p=0.02). %FMD did not differ between the EF and EL phases (9.6±4.4 vs. 9.5±3.5 %, p=0.97). In conclusion, the macrovascular function of healthy premenopausal women is similar between the EF and EL phases despite significant increases in the P4:E2. Findings may suggest that P4 does not play an antagonist role on E2 and may have a synergistic effect on increasing %FMD among decreased concentrations of E2.

Effect of oviductal fluid on bull sperm functionality and fertility under non-capacitating and capacitating incubation conditions

This study investigated the effect of bovine oviductal fluid from late follicular (LF) and early luteal (EL) phases on bull sperm functionality under non-capacitating (NCAP) and capacitating (CAP) conditions. Frozen-thawed semen samples from five bulls were thawed and incubated (0, 1 or 2 h) in NCAP and CAP media supplemented with 1% bovine oviductal fluid (LF and EL groups) and in absence of fluid (C group). Motion parameters were assessed by CASA; sperm viability, acrosomal integrity and membrane lipid disorder parameters were evaluated by flow cytometry; and sperm DNA fragmentation was evaluated by the Comet assay. Finally, in vitro fertilization with sperm treated under CAP conditions was performed and further embryo culture results evaluated. In NCAP medium, addition of LF and EL fluid increased the total and progressive motility, and LF fluid improved the stability of sperm DNA. However, under CAP conditions addition of LF and EL fluid decreased some sperm motion parameters and some parameters of sperm DNA stability. Proportion of viable sperm cells with low lipid disorder was higher in NCAP than CAP medium and addition of LF fluid markedly increased the proportion of viable spermatozoa with high lipid disorder and acrosome alteration (spontaneous acrosome reaction). Under current conditions, incubation of bull sperm with oviductal fluid before insemination did not affect detrimentally the IVF results nor embryo development, being blastocyst rate similar between CAP-LF, CAP-EL and control groups. In conclusion, oviductal fluid positively influences sperm functionality and modulate in vitro capacitation.

Leptin and ghrelin concentrations and eating behaviors during the early and late luteal phase in women with premenstrual dysphoric disorder

ObjectivesIn this study, we evaluated the changes in leptin and ghrelin concentrations, eating behavior, depression, and impulsivity and their correlations within the luteal phase among women with premenstrual dysphoric disorder (PMDD). MethodsIn 63 women with PMDD and 53 healthy controls, we prospectively evaluated serum levels of leptin and ghrelin, Body Mass Index(BMI), and self-reported sweet cravings, cognitive restraint, uncontrolled eating, emotional eating, depression, and impulsivity during the early luteal (EL) and late luteal (LL) phases. ResultsCompared with the controls, the women with PMDD had higher BMI, higher leptin concentrations in the EL and LL phase, and leptin concentrations increased from the EL to the LL phase. However, there is no significant difference in ghrelin. Women with PMDD increased sweet cravings and uncontrolled eating from EL to LL phase. No significant correlation was observed between the EL-LL changes in leptin or ghrelin concentrations and those in eating behaviors. Both depression and impulsivity correlated with sweet craving and uncontrolled eating. Depression mediated the association between PMDD and uncontrolled eating. The BMI of women with PMDD positively correlated with their EL-LL change in leptin, and LL depression levels and emotional eating. ConclusionYoung women with PMDD had higher leptin concentrations and BMI in the luteal phase. The LL leptin level was not the primary factor responsible for the increased uncontrolled eating of PMDD. Whether the increased eating and depression in the LL phase contribute to the risk of obesity or hyperleptinemia among women with PMDD need to be evaluated in the future.

229 From head to tail: A red wolf sperm project

Development of assisted reproductive technologies for the critically endangered red wolf (Canis rufus) is crucial to the maintenance of genetic diversity to support species recovery. Towards this goal, a cryopreservation protocol has previously been developed for red wolf sperm; however, the ability of the gametes to undergo capacitation has not been assessed in this species. Previously, we have shown that oviductal extracellular vesicles (oEVs) improve cat sperm motility and fertilizing ability. The objectives were to (1) compare the effects of culture media on motility and acrosomal integrity of fresh sperm, and select the best medium that can be used in a capacitation protocol; (2) identify potential biomarkers for sperm cryo-tolerance; and (3) determine the influence of canine oEVs on sperm survival and motility post-thaw. In Study 1, sperm were collected by electro-ejaculation from adult red wolves (n=8) and immediately cryopreserved in TRIS-egg yolk buffer with 8% glycerol or incubated for 18h in 5% CO2 and 38.5°C in one of the following media: canine capacitation medium (CCM), FERT-TALP (FERT), NCSU, synthetic oviductal fluid (SOF) and TRIS. At 0, 1, 2, 3, 4, and 18h, sperm were evaluated for total motility and acrosome integrity (FITC-PNA). In Study 2, sperm with high (>80%, HM, n=2 wolves) and low (<15%, LM, n=2 wolves) motility post-incubation at 4°C in the cryopreservation medium for 18h were subjected to proteomic analysis. In Study 3, oviducts were collected from domestic dogs (1-9 years, n=12) after elective spaying, and oEVs from various stages of the oestrous cycle [early follicular (EF), late follicular (LF), early luteal (EL), and late luteal (LL)] were isolated using the Total Exosome Isolation kit (Invitrogen). Frozen-thawed red wolf sperm (n=4 males) were incubated with 30×106 oEVs in non-capacitating CCM, and assessed as in study 1 at 0, 0.5, 1, 2, 3, 4, 6, 8, and 10h. Data were analysed using a paired samples t-test with 95% CI (Prism8, GraphPad Inc.). Sperm incubated in CCM and NCSU had higher motility than those in FERT, SOF, and TRIS after 2h of incubation and onward (2 h: 65±6, 68±6, 42±10, 57±8, and 43±5; 3 h: 60±9, 63±8, 36±11, 46±9, and 34±6; 4 h: 60±9, 60±10, 30±10, 43±8, and 20±5; 18 h: 12±7, 15±7, 9±5, 3±2, and 0, respectively; P<0.05). After 1h of incubation, samples incubated in CCM, NCSU, and SOF had a higher number of sperm with intact acrosomal membranes (P>0.05) than other treatments. A total of 179 proteins were identified, of which 129, including those regulating energy metabolism and mitochondrial mediated apoptosis, were differentially expressed between HM and LM. Preliminary data from Study 3 suggested that thawing and incubating sperm in the presence of LF, EL, and LL oEVs improved sperm motility. In conclusion, CCM and NCSU sustained sperm survival after invitro incubation and could be candidates for invitro fertilization studies in the red wolf. Data generated from sperm proteomic analysis provided insights into cellular pathways regulating sperm cryo-sensitivity. Finally, we demonstrated the potential of oEVs in improving wolf sperm survival post-thawing.

Early- and Late-Luteal-Phase Estrogen and Progesterone Levels of Women with Premenstrual Dysphoric Disorder.

Objective/introduction: The dynamics of ovarian hormone fluctuations during the luteal phase of the menstruation cycle were previously suggested to contribute to the development of premenstrual dysphoric disorder (PMDD) symptoms, but adequate empirical evidence has not been obtained from hormone concentration studies. We prospectively evaluated estrogen and progesterone levels in the early luteal (EL) and late luteal (LL) phases in women with PMDD and the association of these levels with PMDD symptom severity. Methods: 63 women with PMDD and 53 controls without such severe symptoms were evaluated for the estrogen and progesterone levels, and PMDD severity in the EL and LL phases. Results: The results demonstrated that the women with PMDD had a lower EL-phase estrogen level than the controls. Covariant analysis demonstrated that the interaction term between EL-phase estrogen and EL-phase progesterone level was associated with PMDD severity. Among women with lower EL estrogen levels, higher EL-phase progesterone was observed among the women with PMDD versus controls. These results suggest that low EL-phase estrogen level could moderate the provoking effect of EL progesterone in women with PMDD. Overall, these data suggest a possible role of estrogen and progesterone in the development of PMDD symptoms.

Expression of Kisspeptin and its receptor in the hypothalamus of cyclic and acyclic buffalo (Bubalus bubalis)

Kisspeptin (Kiss1), neurokinin-B (NKB) and dynorphin (Dyn) neurons regulate the surge and pulsatile centres of gonadotropin releasing hormone (GnRH) in the hypothalamus and are modulated by the ovarian steroids. Accordingly, we studied the temporospatial expression of Kiss1, its receptor and other genes that regulate GnRH in the preoptic area (POA) and arcuate (ARC) regions of hypothalamus at different phases of bubaline estrous cycle. Brain of buffalo (n = 32) was collected immediately after exsanguination and categorized into early luteal (EL), mid luteal (ML), follicular (FL) stages and acyclic (n = 8/group). Total RNA was extracted from the POA and ARC of each stage and real time PCR amplification of Kiss1, Kiss1r, NKB, NKB receptor (NKBR), Dyn, Dyn receptor (OPRK1), GnRH1, ERα, PR, LEPR and GHSR was done using GAPDH as endogenous control and acyclic stage as calibrator group. Further, immunolocalization of Kiss1 and Kiss1r was done on the hypothalamus. In the POA, significant up-regulation of Kiss1 and NKB with a concomitant down-regulation of Dyn transcripts was recorded at FL stage. There was, however, down-regulation of Kiss1 and Kiss1r during the EL perhaps due to the loss of estradiol as a consequence of ovulation. On the other hand, in the ARC, there was a significant up-regulation of Kiss1 and Dyn at FL and ML, while NKB transcript was consistently down-regulated at any stage of estrous cycle. In the POA, expression of ERα was not modulated; however, PR was down-regulated in the EL. In the ARC, the ERα expression was significantly up-regulated in the EL, whereas, PR was moderately expressed irrespective of the stage of estrous cycle. The immunolocalization study revealed the presence of Kiss1 and Kiss1r in the POA and ARC in the cyclic buffalo with relative abundance at FL. The transcriptional profile of the genes suggests that there is estrous cycle stage specific expression of Kiss1, Kiss1r and other GnRH regulating genes in the POA and ARC regions of hypothalamus in the buffalo. Up-regulation of Kiss1r in the POA during ML and ARC during EL indicates the involvement of kisspeptinergic system in the regulation of low LH pulse frequencies during the early and mid luteal phases in the cyclic buffalo.

P.1.h.051 - Are smarter rats less social? − ‘empathy’ and pro-social behavior in relation to cognitive performance

In this study, we evaluated the changes in leptin and ghrelin concentrations, eating behavior, depression, and impulsivity and their correlations within the luteal phase among women with premenstrual dysphoric disorder (PMDD).In 63 women with PMDD and 53 healthy controls, we prospectively evaluated serum levels of leptin and ghrelin, Body Mass Index(BMI), and self-reported sweet cravings, cognitive restraint, uncontrolled eating, emotional eating, depression, and impulsivity during the early luteal (EL) and late luteal (LL) phases.Compared with the controls, the women with PMDD had higher BMI, higher leptin concentrations in the EL and LL phase, and leptin concentrations increased from the EL to the LL phase. However, there is no significant difference in ghrelin. Women with PMDD increased sweet cravings and uncontrolled eating from EL to LL phase. No significant correlation was observed between the EL-LL changes in leptin or ghrelin concentrations and those in eating behaviors. Both depression and impulsivity correlated with sweet craving and uncontrolled eating. Depression mediated the association between PMDD and uncontrolled eating. The BMI of women with PMDD positively correlated with their EL-LL change in leptin, and LL depression levels and emotional eating.Young women with PMDD had higher leptin concentrations and BMI in the luteal phase. The LL leptin level was not the primary factor responsible for the increased uncontrolled eating of PMDD. Whether the increased eating and depression in the LL phase contribute to the risk of obesity or hyperleptinemia among women with PMDD need to be evaluated in the future.

Relationship between estradiol and progesterone concentrations and cognitive performance in normally cycling female cynomolgus monkeys

Preclinical research has demonstrated that cognitive function may be influenced by estradiol (E2) and progesterone (P4) concentrations, although few cognition studies involve normally cycling females. The present study examined cognitive performance in normally cycling female cynomolgus macaques (n=14), a species with similarities to humans in brain organization and a nearly identical menstrual cycle to women. Initial assessments compared cognitive measures to circulating concentrations of E2 and P4 (n=12). Once a relationship was characterized between hormones and cognitive performance, the menstrual cycle was divided into four distinct phases: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL), verified by the onset of menses and serum concentrations of E2 and P4. Concentrations of E2 were highest during the LF phase and P4 concentrations peaked during the EL phase. All monkeys were trained on two cognitive tasks: reversal learning, involving simple discrimination (SD) and reversal (SDR), which measured associative learning and behavioral flexibility, respectively (n=3–4 per phase) and a delayed match-to-sample (DMS) task which assessed working memory (n=11). P4 concentrations were positively correlated with number of trials and errors during acquisition of SD performance, but not during acquisition of the SDR task or maintenance of the reversal-learning task. Across the menstrual cycle, significantly fewer errors were made in the SDR task during the LF phase, when E2 concentrations were high and P4 concentrations low. Working memory, assessed with the DMS task, was not consistently altered based on previously characterized menstrual cycle phases. These findings demonstrate a relationship between P4, E2 and cognitive performance in normally cycling cynomolgus monkeys that is task dependent. Knowledge of these interactions may lead to a better understanding of sex-specific cognitive performance.

Differential Expression of Leptin and Leptin Receptor mRNA in Obese and Non-Obese Women across the Menstrual Cycle Title

OBJECTIVE: The aim of this study was to investigate the messenger ribonucleic acid expression of leptin (L-mRNA) and the leptin receptor (OB-RmRNA) in subcutaneous fat tissue and to determine their relationship with leptin and testosterone and steroid serum levels over the course of the menstrual cycle (MC), in obese (OBW) and non-obese women (NOW). DESIGN: Observational study investigating mRNA transcript expression of leptin and the leptin receptor from human subcutaneous fat specimens, as well as leptin serum levels, both in relation to the testosterone and sex hormones during the MC in obese and non-obese women. METHODS: Nineteen women, thirteen with a body mass index (BMI) > 25 Kg/m2 and 6 with BMI 2 were included. RT-PCR was used to detect L-mRNA transcripts of leptin and its receptor in samples from 28 fat biopsies taken from seven volunteers (20 from OW and 8 from NOW). The serum concentrations of leptin and steroid hormones were measured throughout the MC using radioinmuno analysis. RESULTS: The percentages of women expressing leptin L-mRNA during the phases of the MC were: early follicular (EF), 14.3%; late follicular (LF), 28.6%; early luteal (EL), 14.3%; and late luteal (LL), 42.9%. The percentages of OB-RmRNA were: EF, 71.4%; LF, 14.3%; EL, 28.6%; and LL, 71.4%. Leptin serum levels were directly related to BMI (p < 0.001), and testosterone (p < 0.001) and indirectly to SHBG (p < 0.001). CONCLUSION: The L-mRNA expression and its receptor in subcutaneous human tissue are regulated throughout the MC in a periodic manner. The physiological role of testosterone in regulation of expression L-mRNA and OB-RmRNA during the secretory phase of the MC in obese women requires further investigation.

320 BASELINE AND SUPEROVULATION HYPERANDROGENISM AND FOLLICULAR DYNAMICS IN THE OSSABAW PIG SUGGEST AN ANIMAL MODEL FOR POLYCYSTIC OVARY SYNDROME

The objective of this study was to validate the obese Ossabaw pig as a model of the obese polycystic ovary syndrome (PCOS) phenotype. Four sows were fed a high fat–high fructose diet to induce metabolic syndrome (MetS), and 5 sows were fed a control diet (Lean). Sows had twice-weekly blood collection and ovarian ultrasound; serum was assessed weekly for androstenedione (A) and twice weekly for progesterone (P). The follicular phase of the oestrous cycle was determined by absence of a corpus luteum on ultrasound and a nadir in P below 2.5 ng mL–1. After baseline measurement collection, sows were down-regulated with a GnRH agonist and superovulated with subcutaneous FSH/LH injections administered every 8 h until large follicles (5–12.5 mm) were visible on the ultrasound (3–7 days), at which point hCG was administered. Oestrous cycle data were divided into follicular (F), early luteal (EL), mid-luteal (ML), late luteal (LL), and transition (T) phases. Superovulation data were subdivided by percentage of stimulation completion and number of days post-hCG. Non-normal data were transformed before analysis with PROC MIXED for repeated-measures in SAS. The MetS sows had a longer average oestrous cycle length than did Lean sows (MetS, 32.2 ± 1.3 days; Lean, 25.2 ± 1.0 days; P &lt; 0.05). In each cycle phase, with the exception of T, MetS A (F: 1.95 ± 0.01 ng mL–1, EL: 1.31 ± 0.07 ng mL–1, ML: 1.14 ± 0.04 ng mL–1, LL: 1.34 ± 0.04 ng mL–1) was higher (P &lt; 0.05) than Lean A (F: 1.11 ± 0.09 ng mL–1, EL: 0.98 ± 0.07 ng mL–1, ML: 0.98 ± 0.04 ng mL–1, LL: 1.04 ± 0.04 ng mL–1). Within the MetS sows, A was significantly higher in F compared with the entire luteal (L) phase (1.25 ± 0.05 ng mL–1; P &lt; 0.05). The MetS sows had similar numbers of large follicles in the F (3.0 ± 1.1 avg pig–1) and L (3.6 ± 1.1 avg pig–1) phases, whereas Lean sows had fewer large follicles during L (0.7 ± 1.1 avg pig–1) compared with F (3.0 ± 1.1 avg pig–1) phase (P &lt; 0.05). The MetS sows had more large follicles than did Lean sows during the EL (MetS, 7.0 ± 1.1, Lean, 0.0 ± 0.0; P &lt; 0.05) and T phases (MetS, 4.0 ± 1.1; Lean, 1.0 ± 1.1; P &lt; 0.05). Lean sows did not form any cystic structures (CS; &gt;12.5 mm). The MetS sows had significantly more CS than did Lean sows during the EL and ML phases (2.0 ± 0.5 avg pig–1; P &lt; 0.05). In response to superovulation, MetS sows had higher A than did Lean sows at completion of stimulation (MetS, 8.45 ± 1.75 ng mL–1; Lean, 2.79 ± 1.36 ng mL–1; P &lt; 0.05) and tended to have higher A than did Lean sows one day post-hCG administration (MetS, 6.00 ± 1.75 ng mL–1; Lean, 2.53 ± 1.36 ng mL–1; P = 0.09). Although not significantly different, MetS sows produced higher numbers of large follicles (range: 9.0–58.6 avg pig–1) than did Lean sows (range: 6.3–33.3 avg pig–1). In conclusion, MetS sows have long oestrous cycles, are hyperandrogenemic, have increased numbers of large follicles in the luteal phase, form cystic structures, and may recruit abnormally high numbers of large follicles in response to superovulation. The obese Ossabaw sow is an excellent animal model in which to study PCOS because women with this disease similarly have oligomenorrhea, hyperandrogenism and ovarian cysts, and recruit high numbers of large follicles at superovulation.

Isometric Knee-Extension and Knee-Flexion Torque Production During Early Follicular and Postovulatory Phases in Recreationally Active Women

Acute decreases in strength have been associated with risky biomechanical strategies that might predispose one to injury. Whether acute changes in thigh muscle torque occur across the menstrual cycle remains equivocal. We compared maximal voluntary isometric contraction (MVIC) torque of the knee flexors and extensors between the early follicular (EF) and either the early luteal (EL) or midluteal (ML) phases, which were confirmed by serum hormone concentrations. We expected that MVIC torques would increase from the EF to the EL phase after estradiol peaked and before increased exposure to progesterone. Cohort study. Applied Neuromechanics Research Laboratory. Seventy-one recreationally active women (age range, 18-30 years). The MVICs were measured 1 day during menses and 1 day during the 8 days after ovulation. Participants were grouped by the hormone profile of their luteal test days as EL phase, ML phase, or anovulatory cycle. The MVIC torque of knee flexors and extensors (Nm/kg), estradiol (pg/mL), progesterone (ng/mL), and testosterone (ng/dL). We tested 29 women during their EL phases, 32 during their ML phases, and 10 during anovulatory cycles. Although we observed relatively large individual changes in sex hormone concentrations and MVIC torques across the 2 test sessions, we observed no difference in MVIC torque between test phases (F(1,68) = 1.17, P = .28) or among groups by test phase (F(2,68) = 0.31, P = .74). Thigh MVIC torque did not change from time of menses (when estradiol and progesterone were lowest) to time in the luteal phase after an unopposed estradiol rise or combined estradiol and progesterone rise. However, these findings were limited to MVIC torque production measured at 2 different times, and further research examining these relationships at multiple times and using other measures of neuromuscular function is needed.

Central, peripheral and resistance arterial reactivity: fluctuates during the phases of the menstrual cycle

The purpose of this study was to document the temporal changes in vascular reactivity occurring simultaneously in central, peripheral and microvascular resistance arteries in the same cohort of women during the normal menstrual cycle. Twenty-three (n = 23) women (mean age (+/-SD) = 19 +/- 1 y) were tested during four phases of a normal menstrual cycle. Delineation of the four phases occurred as follows: (1) the early follicular phase; (2) the late follicular (LF) phase; (3) the early luteal (EL) phase; and (4) the late luteal phase. Non-invasive measurement of central hemodynamics and peripheral artery pulse wave velocity (PWV) were performed using applanation tonometry. Measurement of peripheral endothelial function was determined by flow-mediated dilation (FMD) testing in the brachial artery and venous occlusion plethysmography in the forearm and calf resistance arteries. Additionally, plasma NOx and 17beta-estradiol (E) concentrations were measured. Both central (aortic) and peripheral blood pressure (BP) were lowest (P < 0.05) during the LF phase and BP reduction was sustained (P < 0.05) into the EL phase. The timing and amplitude of the reflected pressure wave were attenuated only during the LF phase (P < 0.05). No temporal changes were observed in either central (carotid-femoral) or peripheral PWV (femoral-dorsalis pedis, carotid-radial). Peak forearm and calf blood flow during reactive hyperemia were greatest in LF. Brachial FMD was greatest during the LF phase (P < 0.05). Plasma E and NOx concentrations were highest during the LF phase (P < 0.05). Young premenopausal women experienced an overwhelming pattern of reduced BP and increased systemic vascular reactivity during the LF phase prior to ovulation.

Sustained attention is favored by progesterone during early luteal phase and visuo-spatial memory by estrogens during ovulatory phase in young women

Studies examining the influence of the menstrual cycle on cognitive function have been highly contradictory. The maintenance of attention is key to successful information processing, however how it co-vary with other cognitive functions and mood in function of phases of the menstrual cycle is not well know. Therefore, neuropsychological performance of nine healthy women with regular menstrual cycles was assessed during ovulation (OVU), early luteal (EL), late luteal (LL) and menstrual (MEN) phases. Neuropsychological test scores of sustained attention, executive functions, manual coordination, visuo-spatial memory, verbal fluency, spatial ability, anxiety and depression were obtained and submitted to a principal components analysis (PCA). Five eigenvectors that accounted the 68.31% of the total variance were identified. Performance of the sustained attention was grouped in an independent eigenvector (component 1), and the scores on verbal fluency and visuo-spatial memory were grouped together in an eigenvector (component 5), which explained 17.69% and 12.03% of the total variance, respectively. The component 1 (p<0.034) and the component 5 (p<0.003) showed significant variations during the menstrual cycle. Sustained attention showed an increase in the EL phase, when the progesterone is high. Visuo-spatial memory was increased, while that verbal fluency was decreased during the OVU phase, when the estrogens levels are high. These results indicate that sustained attention is favored by early luteal phase progesterone and do not covaried with any other neuropsychological variables studied. The influence of the estrogens on visuo-spatial memory was corroborated, and covaried inversely with verbal fluency.

The introduction of rams induces an increase in pulsatile LH secretion in cyclic ewes during the breeding season

Application of the ram effect during the breeding season has been previously disregarded because the ewe reproductive axis is powerfully inhibited by luteal phase progesterone concentrations. However, anovulatory ewes treated with exogenous progestagens respond to ram introduction with an increase in LH concentrations. We therefore tested whether cyclic ewes would respond to ram introduction with an increase in pulsatile LH secretion at all stages of the estrous cycle. We did two experiments using genotypes native to temperate or Mediterranean regions. In Experiment 1 (UK), 12 randomly cycling, North of England Mule ewes were introduced to rams midway through a frequent blood-sampling regime. Ewes in the early (EL; n = 6) and late luteal (LL; n = 6) phase responded to ram introduction with an increase in LH pulse frequency and mean and basal concentrations of LH (at least P < 0.05). In Experiment 2 (Australia), the cycles of 32 Merino ewes were synchronised using intravaginal progestagen pessaries. Pessary insertion was staggered to produce eight ewes at each stage of the estrous cycle: follicular (F), early luteal (EL), mid-luteal (ML) and late luteal (LL). In all stages of the cycle, ewes responded to ram introduction with an increase in LH pulse frequency ( P < 0.01); EL, ML and LL ewes also had an increase in mean LH concentration ( P < 0.05). In conclusion, ram introduction to cyclic ewes stimulated an increase in pulsatile LH secretion, independent of ewe genotype or stage of the estrous cycle.

Fluctuations in carotid arterial distensibility during the menstrual cycle do not influence cardiovagal baroreflex sensitivity

Fluctuations in autonomic nervous functions throughout the menstrual cycle and the underlying mechanism concerning them are not well known. This study was designed to test the hypothesis that fluctuations in cardiovagal baroreflex sensitivity (BRS) throughout the menstrual cycles of young women are due to fluctuations in carotid arterial distensibility. In eight eumenorrhoeic healthy young women (18-24 years), we determined the variations in the carotid arterial distensibility coefficient (DC; via simultaneous ultrasonography and applanation tonometry), cardiovagal BRS (phase IV of the Valsalva manoeuvre and the sequence method; up- or down-sequence spontaneous BRS), and serum oestradiol and progesterone concentrations at five points in the menstrual cycle (menstrual = M, follicular = F, ovulatory = O, early luteal = EL, and late luteal = LL). Serum oestradiol and progesterone levels were consistent with the predicted cycle phases. Carotid arterial DC fluctuated cyclically, increasing significantly from the M (52.4 +/- 4.9 x 10(-3) kPa(-1), mean +/- SE) and F (52.7 +/- 4.4) phases to the O (57.6 +/- 4.4) phase and declining sharply in the EL (46.0 +/- 4.0) and LL (45.1 +/- 3.0) phases (F = 6.37, P < 0.05). Contrary to our prediction, however, cardiovagal BRS by the Valsalva manoeuvre (P = 0.73) or sequence method (up-sequence spontaneous BRS; P = 0.84: down-sequence spontaneous BRS; P = 0.67) did not change significantly during the menstrual cycle. The results suggest that, although carotid arterial distensibility fluctuates with the changes in ovarian hormone levels that occur during the menstrual cycle, the fluctuations in carotid arterial distensibility do not influence cardiovagal BRS.

Performance in a test demanding prefrontal functions is favored by early luteal phase progesterone: an electroencephalographic study

There are some psychological studies showing changes in intellectual efficiency before and during menstruation. Many women report that they experience a feeling of difficulty to initiate activities, confront challenging situations and lack of concentration suggesting transient changes in frontal lobe functions related with gonadal hormone levels. Therefore, performance of a task demanding prefrontal functions, the Wisconsin Card Sorting Test, with simultaneous recording of electroencephalographic (EEG) activity was assessed in 9 healthy women, in a repeated measure study, during ovulation (OVU), early luteal (EL), late luteal (LL) and menstrual (MEN) phases. Spectral power of base line and task EEG, and number of responses to reach successful and unsuccessful outcomes in the task were evaluated. Performance was impaired to a certain degree during the OVU phase and was associated with an attenuated alpha1 power and with an increase of the theta and beta2 power. Performance was better during EL phase, when progesterone level is at its highest, no significant changes were observed from BL to task. Performance was worse during LL phase when hormone levels are at its lowest and was associated with a decrease in beta1 and beta2 power together with a significant attenuation of alpha1 and alpha2 power. During MEN phase performance was also improved and was associated with a significant decrease of alpha1 and alpha2 power and no changes in beta power were observed. These findings show that performance of a task demanding internal attention and planning is modulated by physiological progesterone and estrogen levels during menstrual cycle and is associated with specific EEG profiles.