Normal Cycling Females Research Articles

Proteome of follicular fluid from Murrah buffaloes (Bubalus bubalis): Normal cycling versus repeat-breeder females

Clinical evaluations have shown that repeat breeding is a major cause of infertility in buffaloes. The follicular fluid (FF) composition reflects directly metabolic status and fertility in females. Given this scenario, this study aimed to perform quantitative proteomic analysis of the FF collected from normal cycling (NC) and compared to repeat-breeder females. According to farm records, buffaloes were divided into two groups: normal cycling (NC, n = 7) and repeat-breeder (RB, n = 8) females. After estrus synchronization and using ultrasound-guided ovum pick-up, FF was aspirated from large follicles (˃ 8 mm). Posteriorly, proteins were identified by the shotgun method. A total of 119 proteins were identified and, among theses, three were uncharacterized and a protein (LOC123334375) was identified only in the NC group. The protein HP-25 homolog 2 was expressed only in RB females. The LFQ (label-free quantitation)-intensity of the proteins afamin (AFM), transthyretin (TTR), clotting factor IX (F9) and Xaa-Pro dipeptidase (PEPD) was significantly (P < 0.05) higher in RB than in NC females. In conclusion, the use of quantitative proteomics proved to be an important tool for the study of RB in buffaloes. The identification of HP-25 homolog 2 protein only in the RB females suggests that it can be used as a biomarker for this reproductive disorder. Additionally, an uncharacterized (LOC123334375) protein was identified only in normal cycling females and compensatory oxidative stress proteins were more expressed in repeat-breeders.

Abnormal prolactin secretion is associated with changes in metabolic health biomarkers in acyclic female African elephants (Loxodonta africana)

Circulating prolactin aberrations (chronically high or low concentrations) have been shown to have strong associations with ovarian dysfunction in African female elephants. However, despite the well-established pleiotropic role that prolactin plays in human health, comprehensive metabolic effects from chronically elevated or suppressed prolactin have yet to be investigated in this species. In humans, in addition to amenorrhea, hyperprolactinemic women have shown increased risks for accelerated atherosclerosis, hyperandrogenemia, lowered metabolism, and insulin resistance. The aim of the study was to determine if elephants with long-term abnormal prolactin secretion were also experiencing alterations in metabolic biomarkers. One year of serum samples, collected biweekly, were obtained from female African elephants (n = 74) housed in North American zoos and categorized based on ovarian cyclicity and prolactin status: normal cycling, normal prolactin (NORMAL, n = 25), acyclic, high prolactin (HIGH, n = 25), or acyclic, low prolactin (LOW, n = 24). Each sample was further analyzed for measures of metabolic function, glucose metabolism, and cardiovascular health. Overall, thyroid hormones were significantly lower in both HIGH (TSH, T3, T4) and LOW (TSH) prolactin elephants compared to NORMAL counterparts. Additionally, HIGH prolactin elephants exhibited lower glucose, G:I ratios, and low-density lipoprotein values, but higher cholesterol concentrations compared to normal cycling females. Overall, LOW prolactin elephants exhibited higher body condition scores and G:I ratios, and higher concentrations of insulin, high-density lipoproteins, cortisol and testosterone, but decreased triglyceride values compared to NORMAL elephants in the study. Data suggest that HIGH prolactin elephants may be experiencing hypothyroidism as a comorbidity, whereas LOW prolactin elephants may be exhibiting aspects of insulin resistance, albeit different from human clinical data. Specific studies are suggested that would help elucidate the underlying mechanisms at play and increase our understanding of prolactin’s role in elephant physiology.

Perinatal exposure of pregnant rats to cypermethrin delays testicular descent, impairs fertility in F1 male progeny leading to developmental defects in F2 generation

Cypermethrin (CYP) is a widely used synthetic pyrethroid insecticide and regarded as a potential endocrine disruptor. CYP exposure may pose a great risk to human health including adverse effect on their reproductive functions. This study aimed to delineate the effects of perinatal exposure of rats to CYP on the sexual maturation and fertility of F1 male progeny. Pregnant rats (F0) were gavaged daily with CYP (0, 1, 10, 25 mg/kg BW/day) and Diethylestilbestrol (DES, 10 μg/kg BW/day), as positive control from gestation day 6 to postnatal day 21. The effects of CYP on body weight gain and reproductive functions were evaluated at the Juvenile (PND 22), peri-pubertal (PND 45) and adult (PND 75) stages of development. A significant delay in the age of testicular descent and prepuce separation was observed at 1 and 25 mg/kg doses of CYP. At the same dose level, reproductive organ development and their functions were also affected. A significant alteration in testicular histology, expression of steroid hormone receptors, and circulatory steroid hormones was observed throughout development. Reduced sperm count and motility were observed at PND 75 leading to subfertility and reduced litter size. These adult male rats when cohabitated with unexposed normal cycling females, the F2 fetuses exhibited developmental defects. Taken together, CYP perinatal exposure caused significant long lasting effects of the reproductive functions of F1 generation male rats, which were vertically transmitted to F2 generation leading to developmental defects. The mechanism of transgenerational effects needs to be explored in details.

Recovery of lead-induced suppressed reproduction in male rats by testosterone.

The objective of the present study was to investigate the effects of testosterone in recuperation of lead-induced suppressed reproduction in adult male rats. Lead acetate was administered orally to adult male rats (95±5days) at dosage level of 0.05 and 0.15% for 55days through drinking water and injected intraperitoneally with either testoviron depot at a dose of 4.16mgkg(-1) body weight or vehicle alone on days 1, 7 and 14 respectively. At the end of treatment, control and treated males were cohabited with untreated normal-cycling females. After cohabitation for 5days, all the male rats were killed and weights of reproductive organs were determined. Significant increase in the indices of testis, epididymis, seminal vesicles, vas deferens and prostate glands was observed in testosterone (T)-treated rats when compared to those of lead-exposed rats. Testosterone treatment significantly increased epididymal sperm count, motile spermatozoa, viable spermatozoa and HOS tail-coiled spermatozoa and also the activity levels of testicular 3β- and 17β-hydroxysteroid dehydrogenases when compared to those of lead-exposed males. From the results, it can be hypothesised that supplementation of testosterone mitigated lead-induced suppressed reproduction in male rats.

Serum leptin levels in polycystic ovary syndrome and its relationship with metabolic and hormonal profile in pakistani females.

The study aimed to investigate the levels of serum leptin in PCOS females and to correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety normal cycling (NC) females with matched age and body mass index (BMI) were recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free testosterone, progesterone, thyroid profile, and FBG levels were measured. The mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL ± 1.49 vs 41.78 ± 1.31 ng/mL, P > 0.05); however, leptin levels showed a strong correlation with BMI in PCOS and NC group (r = 0.77, P < 0.0001; r = 0.82, P < 0.0001, resp.). High E2 levels in NC had a significant correlation with leptin whereas FBG correlated with leptin in PCOS (r = 0.51, P = 0.005). TSH had a substantial correlation (r = 0.49, P < 0.005; r = 0.69, P < 0.005) in PCOS and NC, respectively. There was no significant difference found in circulating leptin concentration between PCOS and NC subjects. Leptin levels in PCOS were related with metabolic impairments manifested by disturbance in FBG levels and impairment of reproductive functions in terms of reduced E2 secretion.

Influence of ovarian hormones on cortical spreading depression and its suppression by L-kynurenine in rat.

Migraine is sexually dimorphic and associated in 20–30% of patients with an aura most likely caused by cortical spreading depression (CSD). We have previously shown that systemic L-kynurenine (L-KYN), the precursor of kynurenic acid, suppresses CSD and that this effect depends on the stage of the estrous cycle in female rats. The objectives here are to determine the influence of ovarian hormones on KCl-induced CSD and its suppression after L-KYN by directly modulating estradiol or progesterone levels in ovariectomized rats. Adult female rats were ovariectomized and subcutaneously implanted with silastic capsules filled with progesterone or 17β-estradiol mixed with cholesterol, with cholesterol only or left empty. Two weeks after the ovariectomy/capsule implantation, the animals received an i.p. injection of L-KYN (300 mg/kg) or NaCl as control. Thirty minutes later CSDs were elicited by applying KCl over the occipital cortex and recorded by DC electrocorticogram for 1 hour. The results show that both estradiol and progesterone increase CSD frequency after ovariectomy. The suppressive effect of L-KYN on CSD frequency, previously reported in normal cycling females, is not found anymore after ovariectomy, but reappears after progesterone replacement therapy. Taken together, these results emphasize the complex role of sex hormones on cortical excitability. The CSD increase by estradiol and, more surprisingly, progesterone may explain why clinically migraine with aura appears or worsens during pregnancy or with combined hormonal treatments.

Prenatal di‐n‐butyl phthalate exposure alters reproductive functions at adulthood in male rats

This study was aimed to investigate the reproductive health in adult male rats exposed to di-n-butyl phthalate (DBP) during embryonic development. Pregnant rats were injected with DBP and F1 male rats were weaned and on postnatal day 100, used for mating with normal cycling females to assess reproductive performance. After completion of cohabitation period, rats were analyzed for other reproductive end points. Transplacental exposure to DBP significantly decreased fertility in adult male rats. Prenatal exposure to DBP significantly decreased sperm density, number of motile sperms, viable sperms, and hypoosmotic swelling tail coiled sperms with an increase in morphological abnormalities in sperms. Testicular steroidogenic enzyme activity levels and serum testosterone levels were significantly decreased in rats exposed to DBP during embryonic development. In conclusion, transplacental exposure to DBP impairs male reproductive performance by decreasing steroidogenesis and spermatogenesis.

Delta opioid receptors colocalize with corticotropin releasing factor in hippocampal interneurons

The hippocampal formation (HF) is an important site at which stress circuits and endogenous opioid systems intersect, likely playing a critical role in the interaction between stress and drug addiction. Prior study findings suggest that the stress-related neuropeptide corticotropin releasing factor (CRF) and the delta opioid receptor (DOR) may localize to similar neuronal populations within HF lamina. Here, hippocampal sections of male and cycling female adult Sprague–Dawley rats were processed for immunolabeling using antisera directed against the DOR and CRF peptide, as well as interneuron subtype markers somatostatin or parvalbumin, and analyzed by fluorescence and electron microscopy. Both DOR- and CRF-labeling was observed in interneurons in the CA1, CA3, and dentate hilus. Males and normal cycling females displayed a similar number of CRF immunoreactive neurons co-labeled with DOR and a similar average number of CRF-labeled neurons in the dentate hilus and stratum oriens of CA1 and CA3. In addition, 70% of DOR/CRF dual-labeled neurons in the hilar region co-labeled with somatostatin, suggesting a role for these interneurons in regulating perforant path input to dentate granule cells. Ultrastructural analysis of CRF-labeled axon terminals within the hilar region revealed that proestrus females have a similar number of CRF-labeled axon terminals that contain DORs compared to males but an increased number of CRF-labeled axon terminals without DORs. Taken together, these findings suggest that while DORs are anatomically positioned to modulate CRF immunoreactive interneuron activity and CRF peptide release, their ability to exert such regulatory activity may be compromised in females when estrogen levels are high.

Influence of Estrous Cycle and Gonadal Hormone Depletion on Nociception and Opioid Antinociception in Female Rats of Four Strains

Evidence suggests that gonadal hormones can modulate sensitivity to nociceptive stimuli and opioid antinociception. However, cross-study comparisons addressing the nature of this modulation have been complicated by a number of methodologic factors, including the use of different rodent strains and opioids. The present study examined the influence of estrous cycle and gonadal hormone depletion (ovariectomy) on thermal nociception and opioid antinociception in female F344, Lewis, Long Evans, and Wistar rats. Estrous cycle-dependent differences in nociceptive sensitivity were not observed in any of the strains. Ovariectomy decreased nociceptive sensitivity relative to their intact female counterparts. In normal cycling females, morphine and buprenorphine were generally most potent in metestrus and proestrus and least potent in estrus. The magnitude of these differences was consistently larger with buprenorphine. Ovariectomy increased the antinociceptive potency of morphine and buprenorphine, with this effect also being larger with buprenorphine. These data suggest that in adult females of a number of rat strains, estrous cycle and gonadal hormone depletion modulate the antinociceptive potency of opioids, with the magnitude of this effect being dependent on the type of opioid. In contrast, depletion of gonadal hormones, but not estrous cycle, modulates thermal nociceptive sensitivity in adult female rats. Perspective Gonadal hormones influence opioid antinociception, and this effect is apparent across different genetic backgrounds. These results suggest that the phase of the menstrual cycle might alter the effectiveness of certain opioids administered to relieve pain in women.

Comparative endocrinology of cycling and non-cycling Asian ( Elephas maximus) and African ( Loxodonta africana) elephants

Up to 14% of Asian and 29% of African elephants in captivity are not cycling normally or exhibit irregular cycles based on progestin profiles. To determine if ovarian acyclicity is related to other disruptions in endocrine activity, serum pituitary, thyroid, adrenal, and ovarian hormones in weekly samples collected for 6–25 months were compared between normal cycling ( n=22 each species) and non-cycling ( n=6 Asian; n=30 African) elephants. A subset of cycling females ( n=4 Asian, 7 African) also were blood sampled daily during the follicular phase to characterize the peri-ovulatory period. In normal cycling females, two leutinizing hormone (LH) surges were observed 3 weeks apart during a normal follicular phase, with the second inducing ovulation (ovLH). Serum FSH concentrations were highest at the beginning of the non-luteal phase, declining to nadir concentrations within 4 days of the ovLH surge. FSH remained low until after the ovLH surge and then increased during the luteal phase. A species difference was noted in prolactin secretion. In the African elephant, prolactin was increased during the follicular phase, but in Asian elephants concentrations remained stable throughout the cycle. Patterns of thyroid hormones (thyroid-stimulating hormone, TSH; free and total thyroxine, T4; free and total triiodothyronine, T3) and cortisol secretion were not affected by estrous cycle stage or season in cycling elephants. In non-cycling elephants, there were no fluctuating patterns of LH, FSH, or prolactin secretion. Overall mean concentrations of all hormones were similar to those in cycling animals, with the exception of FSH, prolactin, and estradiol. Mean serum FSH concentrations were lower due to females not exhibiting normal cyclic increases, whereas serum estradiol was higher overall in most acyclic females. Prolactin concentrations were significantly increased in 11 of 30 non-cycling females, all of which were African elephants. In sum, while there were no consistent endocrine anomalies associated with ovarian acyclicity, hyperprolactinemia may be one cause of ovarian dysfunction. The finding of elevated estrogens in some acyclic females also deserves further investigation, especially determining how it relates to reproductive tract pathologies.

Effect of tamoxifen on sperm fertilising ability and preimplantation embryo development

Recent evidences point to a role of estrogens in males. We have earlier reported that tamoxifen, a synthetic non-steroidal antiestrogen, when administered to adult male rats, in the dose range of 0.04–0.4 mg/kg per day, reduced fertility. The reduced fertility was measured in terms of fertility index (a measure of the efficiency of the ovulated ovas to fertilise and implant), fecundity (siring ability) and litter size. The present study was done to investigate whether the reduction in fertility index was due to reduction in fertilising ability or increase in pre-implantation embryo loss. Also a dose related effect of tamoxifen from 0.02 mg to 2 mg/kg per day on the fertility of the male rats was studied. To study the fertilising ability, control and tamoxifen (0.4 mg/kg per day, the most effective dose) treated adult male rats were mated with normal cycling females and the females sacrificed at day 0–4 of gestation. Eggs fertilised/unfertilised were flushed from the oviduct/uterus and the number and types of eggs were noted. The index of fertilisation, a measure of the fertilising ability was determined. The studies demonstrate that the reduction in fertility is not due to decreased fertilising ability but because of the increased pre-implantation embryo loss as evident from an increase in number of abnormal eggs in the treated group with no change in index of fertilisation. A dose related decrease in fertility was observed. The present study suggests that tamoxifen at 0.02–2-mg dose is predominantly estrogenic in males and paternal factor/s sensitive to tamoxifen is involved in embryogenesis.

Prolactin (PRL)-releasing peptide stimulates PRL secretion from human fetal pituitary cultures and growth hormone release from cultured pituitary adenomas.

The hypothalamic peptide PRL-releasing peptide (PrRP) has recently been cloned and identified as a ligand of an orphan pituitary receptor that stimulates in vitro PRL secretion. PrRP also induces PRL release in rats in vivo, especially in normal cycling females. However, no information on the effects of PrRP in the human is available. To elucidate the role of PrRP in regulating human anterior pituitary hormones, we used human PrRP-31 in primary cultures of human pituitary tissues, including fetal (20--27 weeks gestation) and normal adult pituitaries, as well as PRL- and GH-secreting adenomas. PrRP increased PRL secretion from human fetal pituitary cultures in a dose-dependent manner by up to 35% (maximal effect achieved with 10 nM), whereas TRH was slightly more potent for PRL release. Coincubation with estradiol resulted in enhanced fetal PRL response to PrRP, and GH release was only increased in the presence of estradiol. Although PRL secretion from PRL-cell adenomas was not affected by PrRP, PrRP induced PRL release from cultures of a GH-cell adenoma that cosecreted PRL. PrRP enhanced GH release in several GH-secreting adenomas studied by 25--27%, including GH stimulation in a mixed PRL-GH-cell tumor. These results show for the first time direct in vitro effects of PrRP-31 on human pituitary cells. PrRP is less potent than TRH in releasing PRL from human fetal lactotrophs and is unable to release PRL from PRL-cell adenomas in culture, but stimulated GH from several somatotroph adenomas. Thus, PrRP may participate in regulating GH, in addition to PRL, in the human pituitary.

Sialic acid binding protein of human endometrium: its regulation by steroids.

In the present study, we have observed that sialic acid binding protein (SABP - a 54 kDa glycoprotein which was isolated from human endometrial scrapings taken at various stages of the menstrual cycle from normal cycling females and purified to apparent homogeneity and was earlier reported from this laboratory) was found in sufficiently detectable amount in the endometrium of normal cycling women whereas it was found in lesser amount in tissue from women who have recently entered the postmenopause stage. SABP was observed in both follicular and luteal phase of menstrual cycle which was found by western blot analysis. In the de-novo synthesis experiment, synthesis and secretion of SABP was found to be stimulated by estradiol (E2) whereas progesterone (P4) was found to have no significant stimulatory effect on it which was also confirmed by HEC cell culture. In the HEC cell culture, priming of cells with E2 was found to influence the effect of P4 on SABP when it was added 2 h after E2 administration. This was observed by doing immunoprecipitation followed by SDS-PAGE and autoradiography. Hence this report clearly indicates that E2 regulates the synthesis and secretion of 54 kDa SABP from human endometrium. How E2 priming of endometrium influences the effect of P4 on SABP has been discussed.

Otoacoustic Emissions in Normal-Cycling Females

The purpose of this study was to determine if the menstrual cycle influences the amplitude of transient (TEOAEs) and distortion-product (DPOAEs) otoacoustic emissions. Thirteen normal-hearing, normal-cycling females were monitored weekly for 12 weeks. TEOAE and DPOAE amplitudes were analyzed to determine if amplitude changes could be detected and correlated to phases of the menstrual cycle. No systematic amplitude changes were observed, demonstrating that evoked OAEs are unaffected by physiologic changes associated with the menstrual cycle.

Hormonal regulation of connexin-43 in baboon corpora lutea.

The synthesis and secretion of progesterone in the corpus luteum are regulated by both endocrine and paracrine/ autocrine factors which affect the steroidogenic cells. Evidence suggests that these cells communicate via cell-cell junctional proteins, the connexins. Previously we have shown that connexin-43 is expressed in both human and baboon (Papio hamadryus anubis) corpora lutea, with differential expression throughout luteal development, but is not detectable in corpora albicantia. We have examined the effect of human chorionic gonadotropin (hCG), oxytocin, clomiphene citrate and the anti-progesterone onapristone on expression of connexin-43 protein in the early luteal phase 1-5 days after the mid-cycle luteinizing hormone (LH) surge (LH+ 1-5 days), the mid-luteal phase 6-10 days after the LH surge (LH+ 6-10 days), and the late luteal phase 11-15 days after the LH surge (LH+ 11-15 days) in corpora lutea obtained from normal adult cycling females. Connexin-43 was localized by immunohistochemistry in cultured cells from all the three stages. Western blot analysis of the treated cells indicated the presence of two bands at 43 and 45 kDa. The band at 45 kDa was found to be phosphorylated connexin-43, indicating the presence of functional gap junctions. hCG (10 IU/ml) stimulated the expression of connexin-43 throughout luteal development; however, maximum expression occurred in the early luteal phase with a significantly greater expression of the non-phosphorylated protein. In contrast, in the mid-luteal phase, the expression of the phosphorylated protein was predominant. Oxytocin (200 mU/ml) also stimulated connexin-43 expression throughout luteal development with similar effects on the phosphorylated and non-phosphorylated protein in the early and mid-luteal phase; however, compared with hCG, oxytocin had a greater effect on mid-luteal phase connexin-43 expression. In the presence of both hCG and oxytocin, the expression of connexin-43 was significantly higher than the control only in the late luteal phase. Both clomiphene citrate and onapristone suppressed connexin-43 expression, and concomitant addition of hCG did not counteract their effect. In the context of our previous studies, it is concluded that, together with LH/hCG and the steroid hormones, oxytocin is involved in cell-cell contact-dependent communication in the corpus luteum.

Effects of hormone deficiency, androgen therapy and calcium supplementation on bone mineral density in female transsexuals.

A total of 79 healthy female transsexuals, divided into four groups, were involved in this study. Group 1 comprised 15 pre-operated normal cycling females; Group 2, five pre-operated females who were on regular androgen therapy for 1-3 years; Group 3, 27 post-operated females who were on regular androgen therapy for 2-12 years; and Group 4, 32 post-operated females who either had stopped or were on irregular androgen therapy. A bone scan of the lumber spine, at positions L2-L4, was carried out for each subject. A blood sample was taken for measurement of plasma testosterone concentrations. Ten subjects from Group 3 had a repeat bone scan following 10-39 months of calcium supplement (625 mg daily as calcium carbonate); another 10 post-operated females of Group 3 had a repeat bone scan 6-59 months later; and five subjects from Group 4 had a repeat scan following resumption of regular androgen therapy for 17-27 months. The mean +/- SE concentrations of testosterone of Groups 1-4 were, respectively, 0.58 +/- 0.05, 10.1 +/- 2.48, 7.7 +/- 0.98 and 0.99 +/- 0.14 ng/ml. Pre-operated females (Group 2) following 1-3 years of regular androgen therapy had significantly higher BMD and age-matched BMD than corresponding levels in pre-operated normal cycling females in Group 1. While the age-matched BMDs of post-operated females, who were on regular androgen therapy, were not significantly different, the mean BMD was significantly lower than corresponding values in the controls of Group 1. Post-operated females in Group 4 had significantly lower BMDs and age-matched BMDs as compared to corresponding values in controls of Group 1. The BMDs and age-matched BMDs of post-operated females, who were on regular androgen therapy, were significantly raised following daily calcium supplementation for durations ranging from 10-39 months. A repeat bone scan carried out following a lapse of 6-59 months did not reveal any significant change in the BMDs and age-matched BMDs of 10 post-operated females on regular androgen therapy. On the other hand, the BMDs and age-matched BMDs of post-operated females in Group 4 were significantly raised following the resumption of regular androgen therapy for 17-27 months. Results of the present study showed that ovariectomy and remaining in the hormone-deficient state for a sufficiently long duration was associated with a definite loss of bone mass. However, it was shown in this study that the resumption of regular androgen therapy for a sufficient duration could arrest this loss and, additionally, substantially increase the bone mass. Androgen appears to have a potentially greater impact on bone mass than oestrogen. Furthermore, calcium supplementation in a Singaporean population, which is accustomed to a low dietary calcium intake, can assist in the accretion of a higher bone mass in an adult population.

Sex differences in paradoxical sleep: influences of estrus cycle and ovariectomy

Previously, we reported that paradoxical sleep (PS) is sexually dimorphic in mice and rats. Since some early studies indicate that PS is suppressed during proestrus night, it is important to know whether the estrus cycle and accompanying circulating ovarian hormones could explain the sexual dimorphism of PS. To examine this, sleep patterns of male rats were compared with those of normal cycling female rats and ovariectomized females in a 12:12 h light/dark cycle. Slow wave sleep and total sleep time are indistinguishable between the males, cycling females and ovariectomized females. However, normal males display significantly more PS than cycling females during both daytime and nighttime (average of all estrus stages). On the other hand, while ovariectomy has no visible effect on daytime sleep - the sexual dimorphism of PS is unchanged by ovariectomy - during nighttime, ovariectomy produces a selective increase of PS, eliminating the sex difference during the night. In sum, normal cycling females show no change in daytime sleep patterns across the estrus cycle, but have significantly less PS during proestrus nights than during metestrus and diestrus nights. The results indicate that the sex difference in nighttime PS is due to the suppression of PS by ovarian hormones during proestrus and, to a less extent, estrus nights. The sex difference in daytime PS, on the other hand, appears to be independent of circulating ovarian hormones.

Sex differences in paradoxical sleep: influences of estrus cycle and ovariectomy

Previously, we reported that paradoxical sleep (PS) is sexually dimorphic in mice and rats. Since some early studies indicate that PS is suppressed during proestrus night, it is important to know whether the estrus cycle and accompanying circulating ovarian hormones could explain the sexual dimorphism of PS. To examine this, sleep patterns of male rats were compared with those of normal cycling female rats and ovariectomized females in a 12:12 h light/dark cycle. Slow wave sleep and total sleep time are indistinguishable between the males, cycling females and ovariectomized females. However, normal males display significantly more PS than cycling females during both daytime and nighttime (average of all estrus stages). On the other hand, while ovariectomy has no visible effect on daytime sleep - the sexual dimorphism of PS is unchanged by ovariectomy - during nighttime, ovariectomy produces a selective increase of PS, eliminating the sex difference during the night. In sum, normal cycling females show no change in daytime sleep patterns across the estrus cycle, but have significantly less PS during proestrus nights than during metestrus and diestrus nights. The results indicate that the sex difference in nighttime PS is due to the suppression of PS by ovarian hormones during proestrus and, to a less extent, estrus nights. The sex difference in daytime PS, on the other hand, appears to be independent of circulating ovarian hormones.

Purification and characterization of a sperm-binding glycoprotein from human endometrium.

A sialic-acid-binding protein (SABP) was purified to apparent homogeneity from human endometrial scrapings taken at various stages of the menstrual cycle from normal cycling females. The 54 kDa monomer was found to be an O-linked glycoprotein with a total carbohydrate content of 34%. This protein agglutinated washed 2% v/v rabbit red blood cells (RBC) in the presence of calcium. Amongst sialic acids and sialoglycoproteins tested for haemagglutination inhibitory activities, N-glycolyl neuraminic acids and human alpha 1-acid glycoprotein were found to be the most potent, the agglutination activity being totally abolished on desialylation of the RBC in the presence of neuraminidase. Western blot studies showed it to be present in the uterine fluid but absent in normal female serum and in full-term placenta. It was also absent in endometrial homogenates of some cases of unexplained primary infertility. Specific binding studies and Scatchard analysis revealed that 125I-labelled human SABP ligand can bind to human spermatozoa with a Ka = 2.6 x 10(9) M-1, their receptors probably being glycoconjugates having a terminal sialic acid moiety, since the sperm-protein interaction could also be abolished when spermatozoa were desialylated with neuraminidase. The binding occurred specifically on the sperm head plasma membrane and decreased markedly when spermatozoa were previously capacitated in vitro using human serum albumin, implicating the possible loss of a sialoglycoprotein receptor to which the ligand binds during capacitation. The biological importance of this sperm-binding secretory glycoprotein and its functional significance in human reproduction have been discussed.

Sex hormones regulate abr latency

In an effort to characterize more completely the influence of sex hormones on auditory brainstem response (ABR) latency, we evaluated the ABRs of normal male and female subjects and women with previously diagnosed endocrinologic syndromes. We describe ABR latency results from the following subjects: five normal males, nine normally cycling females on no hormonal therapy, nine females using oral contraceptive pills, five females with premature ovarian failure (POF) undergoing cyclic estrogen-progesterone replacement therapy, and five hyperandrogenized females with polycystic ovarian disease (PCOD) treated with the gonadotropin-releasing hormone agonist, Lupron depot, to suppress ovarian steroid production. All subjects were between 23 and 40 years of age. Serum levels of estradiol, progesterone, testosterone, prolactic, and gonadotropins (lutienizing hormone and follicle stimulating hormone) were measured to document the hormonal status of each of the subjects at the time of the ABR evaluation. Normal cycling females and females with POF underwent ABR testing during different phases of the same cycle. Male subjects and females using birth control pills were studied four times in the same month at 1-week intervals. Females with PCOD were also studied four times; baseline and then at 2-week intervals after the initiation of Lupron depot therapy. Increased ABR wave V peak latencies were found to be associated with elevated levels of estrogen or testosterone. We have previously reported a lengthening of ABR wave V peak latencies coincident with peak estrogen levels during the female cycle.(ABSTRACT TRUNCATED AT 250 WORDS)