Effect of Caffeine on the Inflammatory-Dependent Changes in the GnRH/LH Secretion in a Female Sheep Model.

Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood-brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic-pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic-pituitary unit, although its effect appears to be partially dependent on the animal's immune status.

Downregulation of peripheral luteinizing hormone rescues ovariectomy-associated cognitive deficits in APP/PS1 mice.

Alzheimer's disease (AD) is more prevalent in women than men, supposing due to the decline of estrogens in menopause, accompanied by increased gonadotropins such as luteinizing hormone (LH). We and others found that the transcription factor early growth response-1 (EGR1) regulates cholinergic function including the expression of acetylcholinesterase (AChE) and plays a significant role in cognitive decline of AD. Here we investigated in APP/PS1 mice by ovariectomy (OVX) and estradiol (E2) supplementation or inhibition of LH the effect on hippocampus-related cognition and related molecular changes. We found that OVX-associated cognitive impairment was accompanied by increased dorsal hippocampal EGR1 expression, which was rescued by downregulating peripheral LH rather than by supplementing E2. We also found in postmortem AD brains a higher expression of pituitary LH-mRNA and higher EGR1 expression in the posterior hippocampus. Both, in human and mice, there was a significant positive correlation between respectively posterior/dorsal hippocampal EGR1 and peripheral LH expression. We conclude that peripheral increased LH and increased posterior hippocampal EGR1 plays a significant role in AD pathology.

Selenium reduces acrylamide-induced testicular toxicity in rats by regulating HSD17B1, StAR, and CYP17A1 expression, oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

This study investigated the effects of Selenium (Se) on testis toxicity induced by Acrylamide (ACR) in rats. In our study, 50 male adult rats were used, and the rats were divided into five groups; control, ACR, Se0.5 + ACR, Se1 + ACR, and Se1. Se and ACR treatments were applied for 10 days. On the 11th day of the experimental study, intracardiac blood samples from the rats were taken under anesthesia and euthanized. Sperm motility and morphology were evaluated. Dihydrotestosterone, FSH, and LH levels in sera were analyzed with commercial ELISA kits. MDA, GSH, TNF-α, IL-6, and IL-1ß levels and SOD, GPx, and CAT, activities were measured to detect the level of oxidative stress and inflammation in rat testis tissues. Expression analysis of HSD17B1, StAR, CYP17A1, MAPk14, and P-53 as target mRNA levels were performed with Real Time-PCR System technology for each cDNA sample synthesized from rat testis RNA. Testicular tissues were evaluated by histopathological, immunohistochemical, and immunofluorescent examinations. Serum dihydrotestosterone and FSH levels decreased significantly in the ACR group compared to the control group, while LH levels increased and a high dose of Se prevented these changes caused by ACR. A high dose of Se prevented these changes caused by ACR. ACR-induced testicular oxidative stress, inflammation, apoptosis, changes in the expression of reproductive enzymes, some changes in sperm motility and morphology, DNA, and tissue damage, and Se administration prevented these pathologies caused by ACR. As a result of this study, it was determined that Se prevents oxidative stress, inflammation, apoptosis, autophagy, and DNA damage in testicular toxicity induced by ACR in rats.

L-arginine supplementation attenuates ovarian oxidative stress in female rats subjected to chronic intermittent hypoxia.

Background: Systemic and organ-specific oxidative stress triggered by hypoxia is suggested to play a key role in germ cell apoptosis and DNA damage. This study was designed to investigate the impact of chronic intermittent hypoxia (CIH) on female fertility and evaluate the potential antioxidant effect of L-arginine (L-Arg) supplementation. Methods: Adult female rats were allocated into three groups: controls (normoxic), hypoxic and hypoxic supplemented with L-Arg. After 12 weeks; hematocrit value was determined, body weight (BW) and ovarian weight were measured for the calculation of the gonado-somatic index. Plasma levels of luteinizing hormone (LH) and progesterone were estimated. Ovarian tissue malondialdehyde (MDA) and catalase were assessed, and caspase-3 enzyme expression was detected by immunohistochemistry. Results: Compared to controls, CIH resulted in increased oxidative stress in the ovarian tissue, decreased ovarian weight, and increased frequency of irregular cycles and higher plasma level of LH in rats with either regular or irregular ovarian cycles. Histological examination of ovarian sections revealed areas of degeneration, atretic follicles, interstitial edema, congested vessels and inflammatory cell infiltration. Immunohistochemistry confirmed the presence of apoptosis by increased caspase-3 expression. Hypoxic rats pre-treated with L-Arg showed increased BW and ovarian weight, decreased ovarian tissue MDA and plasma LH accompanied by a lower incidence of irregular cycles and mortality. The histological picture was improved and caspase-3 expression was reduced. Conclusion: Oxidative stress caused by CIH is detrimental to the structure and function of the corpus luteum with an increased risk of reduced fertility. L-Arg supplementation increases antioxidant capacity and improves hypoxia-induced fertility disorders.

Influence of Vitamin D on the Incidence of Metabolic Syndrome and Hormonal Balance in Patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that affects 8-13% of women of reproductive age. It is one of the most common causes of infertility and is associated with hyperandrogenism in the form of hirsutism and acne, non-ovulatory cycles, and characteristic ovarian morphology. The available research on serum vitamin D deficiency in patients with PCOS and the appropriateness of vitamin D supplementation in this group of women is inconclusive, so we decided to investigate the influence of vitamin D on the incidence of metabolic syndrome and hormonal balance in patients with polycystic ovary syndrome. The study comprised 120 women aged between 18 and 42 years, who were divided into two groups: a group with diagnosed polycystic ovary syndrome (PCOS) and a group of regularly menstruating women without features of androgenisation, in whom polycystic ovary syndrome was excluded. Each patient underwent a history and physical examination, including a gynecological examination, anthropometric measurements were taken, including height, weight, waist, and hip circumference, and blood pressure was measured using the Korotkow method. In the female patients, the following parameters were also determined from the blood: follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, TSH, ft4, prolactin (PRL), total testosterone, DHEASO4, 17-hydroxyprogesterone (17-OHP), sex-hormone-binding globulin (SHBG), androstendione, 25(OH) vitamin D3 metabolite. The majority of the patients with polycystic ovary syndrome were found to have deficient or suboptimal serum vitamin D levels, and the effects of vitamin D on the SHBG levels and free-androgen indices in these patients was examined. The effects of vitamin D on the incidence of metabolic syndrome and BMI, waist-to-hip ratio, waist circumference, and blood pressure in patients with polycystic ovary syndrome were also found.

Recombinant-luteinzing hormone supplementation in women during IVF/ICSI cycles with GNRH-antagonist protocol: A systematic review and meta-analysis.

The objective of this meta-analysis is to determine the beneficial effect of recombinant-luteinizing Hormone (r-LH) addition in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with gonadotropin-releasing hormone (GnRH) antagonist protocol and whether an optimal time of Recombinant-Luteinizing Hormone (r-LH) supplementation exist during the controlled of stimulation (COS). The primary outcomes are clinical Pregnancy rate and the number of oocytes retrieved. Secondary outcomes are the number of metaphase II oocytes, miscarriage rate and live birth rate. Results show that supplementation of LH generated a greater number of oocytes retrieved than patients who did not receive LH supplementation, but it did not help with other pregnancy outcomes. Furthermore, the result of the subgroup analysis revealed no significant difference in the outcomes with different LH addition times.

The impact of inflammatory stress on hypothalamic kisspeptin neurons: Mechanisms underlying inflammation-associated infertility in humans and domestic animals.

Inflammatory diseases attenuate reproductive functions in humans and domestic animals. Lipopolysaccharide (LPS), an endotoxin released by bacteria, is known to disrupt female reproductive functions in various inflammatory diseases. LPS administration has been used to elucidate the impact of pathophysiological activation of the immune system on reproduction. Hypothalamic kisspeptin neurons are the master regulators of mammalian reproduction, mediating direct stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) release and consequent release of gonadotropins, such as luteinizing hormone (LH) and follicle-stimulating hormone from the pituitary. The discovery of kisspeptin neurons in the mammalian hypothalamus has drastically advanced our understanding of how inflammatory stress causes reproductive dysfunction in both humans and domestic animals. Inflammation-induced ovarian dysfunction could be caused, at least partly, by aberrant GnRH and LH secretion, which is regulated by kisspeptin signaling. In this review, we focus on the effects of LPS on hypothalamic kisspeptin neurons to outline the impact of inflammatory stress on neuroendocrine regulation of mammalian reproductive systems. First, we summarize the attenuation of female reproduction by LPS during inflammation and the effects of LPS on ovarian and pituitary function. Second, we outline the inhibitory effects of LPS on pulsatile- and surge-mode GnRH/LH release. Third, we discuss the LPS-responsive hypothalamic-pituitary-adrenal axis and hypothalamic neural systems in terms of the cytokine-mediated pathway and the possible direct action of LPS via its hypothalamic receptors. This article describes the impact of LPS on hypothalamic kisspeptin neurons and the possible mechanisms underlying LPS-mediated disruption of LH pulses/surge via kisspeptin neurons.

Ovarian stimulation with luteinizing hormone supplementation: the impact of timing on ovarian response and ICSI outcomes.

OBJECTIVE: To investigate whether the timing of rLH addition to rFSH during controlled ovarian stimulation (COS) impacts ovarian response and the outcomes of intracytoplasmic sperm injection (ICSI) cycles. METHODS: Data of 1278 patients undergoing ICSI between 2015 and 2018, in a private university-affiliated IVF center were analyzed. Patients were divided into groups according to the timing of LH addition to the COS protocol: Group LH-start (n=323), in which LH was administered since day 1 of ovarian stimulation; and Group LH-mid (n=955), in which LH was administered concomitantly with gonadotropin releasing hormone (GnRH) antagonist. Data were also stratified according to female age and response to COS. The outcomes of COS and ICSI were compared between the groups. RESULTS: For the general group and in patients aged ≥ 35 years, higher blastocyst development rates were in Group LH-mid compared to Group LH-start. In patients with poor response to COS (POR), higher fertilization rate, blastocyst development rate and implantation rate were observed in Group LH-mid. CONCLUSIONS: rLH supplementation in POR patients may improve laboratorial and clinical outcomes when started in the mid-follicular phase, in GnRH antagonist ICSI cycles.

The Effects of Six-Gram D-Aspartic Acid Supplementation on the Testosterone, Cortisol, and Hematological Responses of Male Boxers Subjected to 11 Days of Nocturnal Exposure to Normobaric Hypoxia.

The aim of this study was to evaluate the effects of D-aspartic acid (DAA) supplementation during a simulated altitude protocol on the hormonal and hematological responses in athletes. We hypothesized that DAA supplementation would contribute to an increase in the luteinizing hormone (LH), free, and testosterone and a greater increase in hematological variables. Sixteen male boxers participated; they were randomly assigned to an experimental group (DAA) or a control group (C) and underwent 14 days of supplementation, 6 g/day of DAA. Both DAA and C participants were exposed to normobaric hypoxia (FiO2 = 15.5%; 2500 m) for 10-12 h a day over a period of 11 days. The results showed that DAA had no significant effect on resting, LH, or the testosterone/cortisol ratio during the training camp. Hypoxic exposure significantly (p < 0.05) increased red blood cell and reticulocyte counts as well as hemoglobin and hematocrit concentrations in both groups, but DAA had no significant effect on these changes. In conclusion, we found that DAA supplementation at a dose of 6 g/day for 14 days does not affect the testosterone, cortisol, or hematological responses of athletes during.

KNDy Neurons of the Hypothalamus and Their Role in GnRH Pulse Generation: an Update.

There is considerable evidence that synchronized activity within a reciprocally connected population of cells in the arcuate nucleus (ARC) coexpressing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy cells) is crucial for the generation of gonadotrophin-releasing hormone (GnRH) pulses in mammals. The initial "KNDy hypothesis" proposed that pulsatile GnRH secretion is elicited by episodic kisspeptin release from KNDy cells following synchronized activation and termination of the population by NKB and dynorphin, respectively. Since then, the role of KNDy cells as a critical component of the pulse generator has been further supported by studies at the single-cell level, demonstrating that the population is both necessary and sufficient for pulsatility. In addition, there have been considerable modifications and expansion of the original hypothesis, including work demonstrating the critical role of glutamate in synchronization of the KNDy cell network, functional interactions with other ARC subpopulations, and the existence of species differences in the role of dynorphin in pulse generation. Here we review these recent changes and discuss how the translation of these findings has led to the development of new therapies for disorders related to pulse generation. We also outline critical gaps in knowledge that are currently limiting the application of KNDy research in the clinic, particularly regarding the role of dynorphin in pulse generation in primates.

An Ovarian Steroid Metabolomic Pathway Analysis in Basal and Polycystic Ovary Syndrome (PCOS)-like Gonadotropin Conditions Reveals a Hyperandrogenic Phenotype Measured by Mass Spectrometry.

Prior work has demonstrated that murine ovarian explants and isolated ovarian follicles can recapitulate human-like 28-day cycles in vitro with normal patterns of estradiol and progesterone secretion in response to gonadotropin stimulation. The objective of this study was to manipulate the gonadotropin stimulation protocol to mimic polycystic ovary syndrome (PCOS) and assess the resulting changes in ovarian steroidogenesis. A secondary aim of the study was to develop a high-throughput, sensitive, and specific liquid chromatography with tandem mass spectrometry (LC-MS/MS) assay to measure seven steroid hormones (estrone, estradiol, progesterone, testosterone, androstenedione, dehydroepiandrosterone, and dihydrotestosterone) in conditioned culture media. Ovaries were harvested from 12-day-old CD-1 mice and cultured for 28 days, with ovulation induction on culture day 14. Media were supplemented human chorionic gonadotropin (hCG, a luteinizing hormone analog) and follicle stimulating hormone (FSH) at ratios of 1:0 (standard media), 1:1 (physiologic ratio), and 3:1 (PCOS-like ratio). Ovaries cultured in PCOS-like media displayed hyperandrogenism and impaired ovulation, two key features of a PCOS-like phenotype. Taken together, this first-of-its-kind presentation of hormone levels from single tissues creates a map of the enzymatic steps most acutely affected by gonadotropin dysregulation and may provide opportunities for assessing other potential insults in PCOS pathogenesis.

Hypothalamic Expression of Estrogen Receptor Isoforms Underlies Estradiol Control of Luteinizing Hormone in Female Rats.

Luteinizing hormone (LH) secretion during the ovarian cycle is governed by fluctuations in circulating estradiol (E2) that oppositely regulate kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) of the hypothalamus. However, how these effects are orchestrated to achieve fertility is unknown. Here, we have tested the hypothesis that AVPV and ARC neurons have different sensitivities to E2 to coordinate changes in LH secretion. Cycling and ovariectomized rats with low and high E2 levels were used. As an index of E2 responsiveness, progesterone receptor (PR) was expressed only in the AVPV of rats with high E2, showing the preovulatory LH surge. On the other hand, kisspeptin neurons in the ARC responded to low E2 levels sufficient to suppress LH release. Notably, the Esr1/Esr2 ratio of gene expression was higher in the ARC than AVPV, regardless of E2 levels. Accordingly, the selective pharmacological activation of estrogen receptor α (ERα) required lower doses to induce PR in the ARC. The activation of ERß, in turn, amplified E2-induced PR expression in the AVPV and the LH surge. Thus, ARC and AVPV neurons are differently responsive to E2. Lower E2 levels activate ERα in the ARC, whereas ERß potentiates the E2 positive feedback in the AVPV, which appears related to the differential Esr1/Esr2 ratio in these 2 brain areas. Our findings provide evidence that the distinct expression of ER isoforms in the AVPV and ARC plays a key role in the control of periodic secretion of LH required for fertility in females.

Regulation of cellular communication network factor 1 by Ras homolog family member A in bovine steroidogenic luteal cells.

Development of the corpus luteum (CL) requires the growth of a new capillary network from preexisting vasculature, a process known as angiogenesis. Successful building of this capillary network occurs through a sequence of cellular events-differentiation, proliferation, migration, and adhesion-which are regulated by a suite of angiogenic proteins that includes cellular communication network factor 1 (CCN1). We previously reported that the expression of CCN1 was highest in luteal tissue obtained from the early-cycle, 4-d-old bovine CL (i.e., corpus hemorrhagicum) compared to the mid- and late-cycle CL. In the present study, we treated steroidogenic bovine luteal cells from early-cycle CL with luteinizing hormone (LH), but it had no effect on CCN1 expression. Direct stimulation of the canonical LH pathway with forskolin and dibutyryl-cyclic adenosine monophosphate (cAMP), however, inhibited CCN1 mRNA expression. In endothelial cells, stimulation of Ras homolog family member A (RhoA) induces CCN1 expression, whereas RhoA inactivation inhibits it. Yet, it is unknown if regulation of CCN1 in steroidogenic luteal cells works likewise. We hypothesized that a similar mechanism of CCN1 regulation exists in bovine luteal cells and that thrombin, a known RhoA activator, may be a physiologic trigger for this mechanism in the early-cycle CL. To test this hypothesis, ovaries were collected from lactating dairy cows on days 3 or 4 of the estrous cycle, and corpora lutea were dissected and dissociated. Steroidogenic luteal cells were suspended in defined Ham's F12 medium, supplemented with insulin/transferrin/selenium and gentamicin, and seeded into 6-well plates. After 24 h, spent medium was replaced with fresh Ham's F12, and the cells were cultured for 24 to 48 h. Cells were treated for 2 h with defined medium, 10% fetal bovine serum (FBS), thrombin (1, 5, 10 U/mL), or Rho Activator II (0.25, 1, 2 µg/mL). Cells were then lysed for RNA extraction, followed by cDNA generation, and quantitative polymerase chain reaction (qPCR). Thrombin (1, 5, 10 U/mL; n = 3) and Rho Activator II (0.25, 1, 2 µg/mL; n = 6) increased (P < 0.05) CCN1 mRNA expression. In summary, CCN1 in bovine steroidogenic luteal cells was induced by thrombin and appeared to be regulated in a Rho-dependent manner. Future work will elucidate the signaling partners downstream of Rho which leads to CCN1 gene expression.

The corpus luteum (CL) is a transient ovarian endocrine gland that secretes progesterone, the hormone of pregnancy. Development of an optimally functioning CL requires the creation of a dense capillary bed through growth of new blood vessels, which is an intricate process called angiogenesis. A myriad of factors regulates angiogenesis, including the angiogenic inducer protein, cellular communication network factor 1 (CCN1). Although it is highly expressed in the early-cycle bovine CL, the mechanisms of CCN1 regulation have not been fully elucidated. In the present study, we showed that CCN1 expression in steroidogenic luteal cells from the early-cycle bovine CL was induced by Ras homolog family member A (RhoA) and by thrombin, but not by luteinizing hormone (LH). To the best of our knowledge, the involvement of thrombin and its signaling partner, RhoA, in regulating CCN1 in bovine steroidogenic luteal cells has not been previously reported. These findings will inform our future work to determine how RhoA activation by thrombin leads to increased expression of CCN1.

Gonadotropin-releasing hormone (GnRH) measurements in pituitary portal blood: A history.

Much about the neuroendocrine control of reproduction is inferred from changes in the episodic release of luteinizing hormone (LH), as measured in samples of peripheral blood. This, however, assumes that LH precisely mirrors gonadotropin-releasing hormone (GnRH) release from the hypothalamus. Because GnRH is not measurable in peripheral blood, characterization of the relationship between these two hormones required the simultaneous measurement of GnRH and LH in pituitary portal and peripheral blood, respectively. Here, we review the history of why and how portal blood collection was developed, the aspects of the true output of the central component of the hypothalamic-pituitary-gonadal axis that this methodology helped clarify, and conditions under which the pituitary fails to serve as an adequate bioassay for the release pattern of GnRH.

Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge.

For billions of years before electric light was invented, life on Earth evolved under the pattern of light during the day and darkness during the night. Through evolution, nearly all organisms internalized the temporal rhythm of Earth's 24-hour rotation and evolved self-sustaining biological clocks with a ~24-hour rhythm. These internal rhythms are called circadian rhythms, and the molecular constituents that generate them are called molecular circadian clocks. Alignment of molecular clocks with the environmental light-dark rhythms optimizes physiology and behavior. This phenomenon is particularly true for reproductive function, in which seasonal breeders use day length information to time yearly changes in fertility. However, it is becoming increasingly clear that light-induced disruption of circadian rhythms can negatively impact fertility in nonseasonal breeders as well. In particular, the luteinizing hormone surge promoting ovulation is sensitive to circadian disruption. In this review, we will summarize our current understanding of the neuronal networks that underlie circadian rhythms and the luteinizing hormone surge.

Evaluation of fertility and embryo implantation in rats after the oral administration of Salvia officinalis (sage) extract / Evaluación de la fertilidad y la implantación de embriones en ratas después de la administración oral de extracto de Salvia officinalis (salvia)

SUMMARY: In Saudi Arabia, it is widely believed that women with reproductive problems can use the extract of the sage plant as a tea drink. This study was conducted to investigate the effects of this herb on the fertility of female rats and embryo implantation. Forty-eight Wistar virgin female rats were divided into four groups at random, with 12 rats in each group. The control group received distilled water orally. The three treatment groups received different concentrations of sage extract: 15, 60, or 100 mg/kg for 14 days before mating, then mated with a male and sacrificed on the 7th day of gestation, the uterine horns removed, and photographed. The total body weight of mothers, weight of uteri and ovaries and number of fetuses were determined. Ovarian and uteri tissues were cut into 5 µ sections and stained with hematoxylin and eosin. Serum FSH, LH were determined by the ELISA method. The present study showed that low dose of sage (15 mg/kg) have no effects on serum concentration levels of FSH and LH hormones, also has no effect on the number of growing follicles. The present study showed a significant differences (P≤0.05) in body weight, ovary and uterus weight in the groups treated with high doses of Salvia officinalis as compared to control group. Also a significant differences (P≤0.05) found in FSH, LH hormones. Histological study showed overall histomorphological structural configurations including growing and matured graafian follicular countable changes, besides a number of corpora lutea and regressed follicles in the treated groups with high doses of Salvia officinalis as compared to control group. The researchers concluded that the extract of the sage plant with high doses can stimulate the growth graafian follicles and improve fertility in female rats.

RESUMEN: En Arabia Saudita, se cree ampliamente que las mujeres con problemas reproductivos pueden usar el extracto de la planta de salvia como bebida de té. Este estudio se realizó para investigar los efectos de esta hierba sobre la fertilidad de las ratas hembra y la implantación del embrión. Se dividieron cuarenta y ocho ratas hembra vírgenes Wistar en cuatro grupos al azar, con 12 ratas en cada grupo. El grupo control recibió agua destilada por vía oral. Los tres grupos de tratamiento recibieron diferentes concentraciones de extracto de salvia: 15, 60 o 100 mg/kg durante 14 días antes del apareamiento, luego se aparearon con un macho y se sacrificaron el día 7 de gestación, se extrajeron los cuernos uterinos y se fotografiaron. Se determinó el peso corporal total de las madres, el peso del útero y los ovarios y el número de fetos. Los tejidos ováricos y uterinos se cortaron en secciones de 5 µ y se tiñeron con hematoxilina y eosina. FSH sérica, LH se determinaron por el método ELISA. El presente estudio mostró que dosis bajas de salvia (15 mg/kg) no tienen efectos sobre los niveles de concentración sérica de las hormonas FSH y LH, tampoco tienen efecto sobre el número de folículos en crecimiento. El presente estudio mostró diferencias significativas (P≤0,05) en el peso corporal, peso de ovario y útero en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo control. También se encontraron diferencias significativas (P≤0,05) en las hormonas FSH, LH. El estudio histológico mostró configuraciones estructurales histomorfológicas generales que incluyen cambios contables en los folículos maduros (de Graaf) y en crecimiento, además de una cantidad de cuerpos lúteos y folículos en regresión en los grupos tratados con altas dosis de Salvia officinalis en comparación con el grupo de control. Los investigadores concluyeron que el extracto de la planta de salvia en altas dosis puede estimular el crecimiento de los folículos maduros y mejorar la fertilidad en ratas hembra.

A mechanistic evaluation of the potential for octamethylcyclotetrasiloxane to produce effects via endocrine modes of action.

This review is a hypothesis driven, mechanistic evaluation of the potential for octamethylcyclotetrasiloxane (D4) to produce any effects via endocrine modes of action. D4 is a volatile, lipophilic liquid used in the production of high molecular weight dimethylsiloxane polymers. These are used in a variety of industrial, medical, cleaning, and personal care products, and they may contain low levels of residual D4. Low concentrations of D4 are found in the environment and there is potential for low level human exposure. All of the measured environmental and workplace levels of D4 fall below no observed effect levels (NOEL). Most of the effects of high dose D4 involve the female reproductive system. In the mature intact female rat following chronic high dose exposure, D4 may cause inhibition of mating and ovulation, decreased live litter sizes, small increases in the estrogen to progesterone ratio primarily through decreases in progesterone, and increases in uterine hyperplasia. When endogenous estrogens are very low, high dose D4 causes increases in some uterine parameters. To assess whether these high dose effects can be attributed to an endocrine mode of action, endpoints are ranked for relevance and strength, consistent with published concepts. When sufficient information is available the level of activity of D4 for producing the observed effect is compared with that of potent endocrines. The conclusions reached are that all of the effects of D4 fall well short of any established criteria for D4 to be capable of producing any adverse effect via an endocrine mode of action.

Reproductive Regulation of PrRPs in Teleost: The Link Between Feeding and Reproduction.

Prolactin-releasing peptide (PrRP), a sort of vital hypothalamic neuropeptide, has been found to exert an enormous function on the food intake of mammals. However, little is known about the functional role of PrRP in teleost. In the present study, two PrRP isoforms and four PrRP receptors were isolated from grass carp. Ligand-receptor selectivity displayed that PrRP1 preferentially binds with PrRP-R1a and PrRP-R1b, while PrRP-R2a and PrRP-R2b were special receptors for PrRP2. Tissue distribution indicated that both PrRPs and PrRP-Rs were highly expressed in the hypothalamus-pituitary-gonad axis and intestine, suggesting a latent function on food intake and reproduction. Using grass carp as a model, we found that food intake could significantly induce hypothalamus PrRP mRNA expression, which suggested that PrRP should be also an anorexigenic peptide in teleost. Interestingly, intraperitoneal (IP) injection of PrRPs could significantly induce serum luteinizing hormone (LH) secretion and pituitary LHß and GtHα mRNA expression in grass carp. Moreover, using primary culture grass carp pituitary cells as a model, we further found that PrRPs could directly induce pituitary LH secretion and synthesis mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways. Finally, estrogen treatment of prepubertal fish elicited increases in PrRPs and PrPR receptors expression in primary cultured grass carp hypothalamus cells, which further confirmed that the PrRP/PrRPR system may participate in the neuroendocrine control of fish reproduction. These results, taken together, suggest that PrRPs might act as a coupling factor in feeding metabolism and reproductive activities in teleost.

The human hypothalamic kisspeptin system: Functional neuroanatomy and clinical perspectives.

In mammals, kisspeptin neurons are the key components of the hypothalamic neuronal networks that regulate the onset of puberty, account for the pulsatile secretion of gonadotropin-releasing hormone (GnRH) and mediate negative and positive estrogen feedback signals to GnRH neurons. Being directly connected anatomically and functionally to the hypophysiotropic GnRH system, the major kisspeptin cell groups of the preoptic area/rostral hypothalamus and the arcuate (or infundibular) nucleus, respectively, are ideally positioned to serve as key nodes which integrate various types of environmental, endocrine, and metabolic signals that can influence fertility. This chapter provides an overview of the current state of knowledge on the anatomy, functions, and plasticity of brain kisspeptin systems based on the wide literature available from different laboratory and domestic species. Then, the species-specific features of human hypothalamic kisspeptin neurons are described, covering their topography, morphology, unique neuropeptide content, plasticity, and connectivity to hypophysiotropic GnRH neurons. Some newly emerging roles of central kisspeptin signaling in behavior and finally, clinical perspectives, are discussed.

Verbascoside attenuates experimental varicocele-induced damage to testes and sperm levels through up-regulation of the hypothalamus-pituitary-gonadal (HPG) axis.

CONTEXT: Verbascoside (VB), which is found in many medicinal plant families, exhibits biological activities in various diseases. However, its effects on varicocele (VCL)-induced damage remain unknown. OBJECTIVE: To investigate the effects and mechanism of VB on experimental rats with varicocele (VCL)-induced damage. MATERIALS AND METHODS: Sixty sexually mature male Sprague-Dawley (SD) rats were divided into six groups (n = 10): control, control-sham, VCL-vehicle (normal saline), and VCL + VB groups (50, 100, and 200 mg/kg/day, intraperitoneally). After 4 weeks of VB treatment, all animals were sacrificed, and the body and testicular weight, sperm quality parameters, histopathology, antioxidant status, and hormone levels were tested. The levels of gonadotropin-releasing hormone (GnRH) and gonadotropin-inhibitory hormone in the hypothalamus were detected by western blot. RESULTS: Compared with the VCL-vehicle group (41.14%), administration of VB significantly increased the sperm viability (59.29, 65.45, 84.93%). VB groups showed higher Johnson's score (3.57 ± 0.15, 4.71 ± 0.26, 7.93 ± 0.37) than VCL-vehicle group (2.72 ± 0.24). Antioxidant status and hormone levels alterations were also observed. Meanwhile, the mean number of apoptotic tubules (8.15 ± 0.96, 6.61 ± 1.05, 2.17 ± 0.08) and apoptotic index showed a marked decrease. Compared with the VCL-vehicle group (0.21 ± 0.09), the VB groups (0.36 ± 0.07, 0.42 ± 0.06, 0.88 ± 0.10) showed considerable increases in GnRH. DISCUSSION AND CONCLUSIONS: VB has protective effects on reproductive organs and VB may be therapeutically useful in the treatment of varicocele through up-regulation of the HPG axis.