scholarly journals Specialized Subpopulations of Kisspeptin Neurons Communicate With GnRH Neurons in Female Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Devesh Kumar ◽  
Michael Candlish ◽  
Vinod Periasamy ◽  
Nergiz Avcu ◽  
Christian Mayer ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Reproductive Physiology ◽  
The Other ◽  
Functional Specialization ◽  
Neuron Population ◽  
Female Mice ◽  
Reproductive Maturation ◽  
Neuron Populations ◽  
Periventricular Nucleus ◽  
Gnrh Neurons

Abstract The neuropeptide kisspeptin is a potent stimulator of GnRH neurons and has been implicated as a major regulator of the hypothalamus-pituitary-gonadal axis. There are mainly two anatomically segregated populations of neurons that express kisspeptin in the female hypothalamus: one in the anteroventral periventricular nucleus (AVPV) and the other in the arcuate nucleus (ARC). Distinct roles have been proposed for AVPV and ARC kisspeptin neurons during reproductive maturation and in mediating estrogen feedback on the hypothalamus-pituitary-gonadal axis in adults. Despite their pivotal role in the regulation of reproductive physiology, little is known about kisspeptin neuron connectivity. Although previous data suggest heterogeneity within the AVPV and ARC kisspeptin neuron populations, how many and which of these potential kisspeptin neuron subpopulations are actually communicating with GnRH neurons is not known. Here we used a combinatorial genetic transsynaptic tracing strategy to start to analyze the connectivity of individual kisspeptin neurons with the GnRH neuron population in female mice with a single-cell resolution. We find that only subsets of AVPV and ARC kisspeptin neurons are synaptically connected with GnRH neurons. We demonstrate that the majority of kisspeptin neurons within the AVPV and ARC does not communicate with GnRH neurons. Furthermore, we show that all kisspeptin neurons within the AVPV connected to GnRH neurons are estrogen sensitive and that most of these express tyrosine hydroxylase. Our data demonstrate functional specialization within the two kisspeptin neuron populations.

Chemical and Cold Sensitivity of Two Distinct Populations of TRPM8-Expressing Somatosensory Neurons

2006 ◽  
Vol 95 (2) ◽  
pp. 1221-1230 ◽  
Author(s):  
Hong Xing ◽  
Jennifer Ling ◽  
Meng Chen ◽  
Jianguo G. Gu
Keyword(s):  
Sodium Channels ◽  
The Other ◽  
Cold Sensitivity ◽  
Single Type ◽  
Drg Neurons ◽  
Neuron Population ◽  
Nociceptive Neurons ◽  
Neuron Populations ◽  
Low Concentrations ◽  
Somatosensory Neurons

The cold- and menthol-sensing TRPM8 receptor has been proposed to have both nonnociceptive and nociceptive functions. However, one puzzle is how this single type of receptor may be used by somatosensory neurons to code for two distinct sensory modalities. Using acutely dissociated rat dorsal root ganglion (DRG) neurons without culture, we show that TRPM8 receptors are expressed on two distinct classes of somatosensory neurons. One class is sensitive to menthol and features nonnociceptive neuron properties, including capsaicin-insensitive, ATP-insensitive, transient acid response, and expression of TTX-sensitive sodium channels only. This class is termed the menthol-sensitive/capsaicin-insensitive neuron class (MS/CIS). The other class is also sensitive to menthol but has characteristics of nociceptive neurons including capsaicin-sensitive, ATP-sensitive, prolonged acid response, and expression of both TTX-sensitive and TTX-resistant sodium channels. This class is termed the menthol-sensitive/capsaicin-sensitive neuron class (MS/CS). The presence of these two neuron classes in acutely dissociated DRG neurons support the idea that TRPM8 receptors can have both nonnociceptive and nociceptive functions. While both neuron classes respond to menthol and cold, the overall responses induced by menthol and cold are significantly larger in MS/CIS than in MS/CS neurons. Furthermore, low concentrations of menthol produce strong selection of the MS/CIS neuron population over the MS/CS neuron population. On the other hand, the population selection becomes weaker with higher concentrations of menthol. TRPM8 current density shows significant higher in MS/CIS neurons than in MS/CS neurons, suggesting different expression levels of TRPM8 receptors between the two neuron populations, and this difference may provide a mean of selective activation of MS/CIS neurons at low stimulation intensity.

scholarly journals SUN-244 Role of Activin, Follistatin, and Inhibin in the Regulation of KISS-1 Gene Expression in Hypothalamic Cell Models

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Aki Oride ◽  
Haruhiko Kanasaki ◽  
Zolzaya Tumurgan ◽  
Tuvshintugs Tumurbaatar ◽  
Satoru Kyo
Keyword(s):  
Gene Expression ◽  
Arcuate Nucleus ◽  
Cell Model ◽  
Gonadotropin Releasing Hormone ◽  
The Other ◽  
Cell Models ◽  
Inhibin A ◽  
Hpg Axis ◽  
Periventricular Nucleus

Abstract Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1-expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin αsubunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.

scholarly journals OR16-01 The Expression of the Homeodomain Transcription Factor SIX3 within Kisspeptin Neurons Is Necessary for Reproduction in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Shanna N Lavalle ◽  
Jacqueline Hernandez ◽  
Pamela L Mellon
Keyword(s):  
Transcription Factor ◽  
Estrous Cycle ◽  
Arcuate Nucleus ◽  
Homeodomain Transcription Factor ◽  
Female Mice ◽  
Gnrh Neurons ◽  
Cycle Lengths ◽  
Single Allele ◽  
Reproductive Processes

Abstract The homeodomain transcription factor SIX3 is necessary for normal reproductive processes in mice. The loss of a single allele results in haploinsufficient phenotypes that are reflective of individuals with Kallmann Syndrome, such as hypogonadism, reduced GnRH neurons, and anosmia. Six3 heterozygous mice have reproductive impairments including an increased time to first litter, increased estrous cycle lengths in females, and fewer litters in males compared to wildtype controls. Prior studies found that deleting SIX3 specifically from GnRH neurons did not recapitulate the same phenotypes produced from a global knockout of the Six3 allele and imposed no reproductive abnormalities. This suggests that the role of SIX3 in reproduction is due to SIX3 populations outside of GnRH neurons. Using qPCR and RNA-seq, we have verified that Six3 is expressed in arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) populations of kisspeptin neurons and can regulate the kisspeptin promoter in vitro. This led us to hypothesize that SIX3 in kisspeptin neurons is required for Kiss1 regulation and maximal fertility. We selectively deleted Six3 from kisspeptin neurons by crossing a Six3-floxed mouse with a Kiss1-Cre mouse to produce Six3 flox/flox; Kiss1-Cre positive mice (cKO) and Six3 flox/flox, Kiss-Cre negative littermates (controls). In female mice, we found that the loss of SIX3 from kisspeptin neurons disrupted the estrous cycle and reduced fertility. Compared to controls, cKO mice had fewer cycles in a 16-day period (0.38 vs 1.44; p=0.004; n=8-9), and spent a greater percentage of time in diestrus (80.5 vs 61.8; p=0.002; n=8-9) and a smaller percentage of time in estrus (15.6 vs 29.2; p=0.030; n=8-9). The loss of kisspeptin-specific SIX3 also resulted in reduced fecundity, with the cKO female mice having fewer pups within 90 days (15.0 vs 34.4; p=0.048; n=5-6) compared to controls. In addition to its importance in female mice, kisspeptin-specific SIX3 also plays a role in male fertility. We found that male cKO mice had reduced motile sperm (52.2% vs 72.5%; p=0.012; n=7-9) compared to controls. We also assayed levels of Kiss1 mRNA in the male arcuate nucleus and observed decreased Kiss1 levels compared to controls (0.34 vs 1.01; p=0.042; n=3-4). These results support our hypothesis that SIX3 in kisspeptin neurons is necessary for critical reproductive processes in both females and males, including progression through the estrous cycle, fecundity, and sperm motility, potentially through Kiss1 regulation.

HUMAN URINARY GONADOTROPHINS ASSAYED BY DIFFERENT RESPONSES IN THE SAME ANIMAL

1960 ◽  
Vol XXXIV (III) ◽  
pp. 375-389 ◽  
Author(s):  
P. S. Brown
Keyword(s):  
Postmenopausal Women ◽  
Ovarian Response ◽  
The Other ◽  
Relative Potency ◽  
Vaginal Opening ◽  
Serial Sections ◽  
Immature Female ◽  
Female Mice ◽  
Marked Disparity ◽  
Relative Potencies

ABSTRACT Selected human urinary gonadotrophins were assayed against one another using various measures of response in the same immature female mice. Intact or hypophysectomized animals were used and in some experiments the results of hypophysectomy were checked in complete serial sections. Extracts from the urine of two subjects with Turner's syndrome were compared. In intact mice, the relative potency judged by the ovarian response differed from that shown by the uterine response and the 95 % fiducial limits of the two estimates did not overlap. When the mice were hypophysectomized, one extract became much less potent while the other did not. Similar differences were shown in the response of intact mice to urinary extracts from two subjects with Klinefelter's syndrome. There was a marked disparity between the relative potencies shown by the uterine response and by the incidence of vaginal opening. Similar differences were not shown between the responses to different extracts from the urine of normal postmenopausal women, but these extracts were known to differ little in quality. The results are interpreted in terms of qualitative differences between human urinary gonadotrophins.

scholarly journals Expression of type one cannabinoid receptor in different subpopulation of kisspeptin neurons and kisspeptin afferents to GnRH neurons in female mice

2021 ◽  
Author(s):  
Tamás Wilheim ◽  
Krisztina Nagy ◽  
Mahendravarman Mohanraj ◽  
Kamil Ziarniak ◽  
Masahiko Watanabe ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Third Ventricle ◽  
Glutamate Transporter ◽  
Neuroendocrine Cells ◽  
Receptor Protein ◽  
Specific Expression ◽  
Female Mice ◽  
Gnrh Neurons ◽  
Periventricular Area ◽  
Cycle Dependent

AbstractThe endocannabinoids have been shown to target the afferents of hypothalamic neurons via cannabinoid 1 receptor (CB1) and thereby to influence their excitability at various physiological and/or pathological processes. Kisspeptin (KP) neurons form afferents of multiple neuroendocrine cells and influence their activity via signaling through a variation of co-expressed classical neurotransmitters and neuropeptides. The differential potency of endocannabinoids to influence the release of classical transmitters or neuropeptides, and the ovarian cycle-dependent functioning of the endocannabinoid signaling in the gonadotropin-releasing hormone (GnRH) neurons initiated us to study whether (a) the different subpopulations of KP neurons express CB1 mRNAs, (b) the expression is influenced by estrogen, and (c) CB1-immunoreactivity is present in the KP afferents to GnRH neurons. The aim of the study was to investigate the site- and cell-specific expression of CB1 in female mice using multiple labeling in situ hybridization and immunofluorescent histochemical techniques. The results support that CB1 mRNAs are expressed by both the GABAergic and glutamatergic subpopulations of KP neurons, the receptor protein is detectable in two-thirds of the KP afferents to GnRH neurons, and the expression of CB1 mRNA shows an estrogen-dependency. The applied estrogen-treatment, known to induce proestrus, reduced the level of CB1 transcripts in the rostral periventricular area of the third ventricle and arcuate nucleus, and differently influenced its co-localization with vesicular GABA transporter or vesicular glutamate transporter-2 in KP neurons. This indicates a gonadal cycle-dependent role of endocannabinoid signaling in the neuronal circuits involving KP neurons.

Some effects of the diet of mice on Nematospiroides dubius (Nematoda)

Parasitology ◽  
1969 ◽  
Vol 59 (1) ◽  
pp. 203-213 ◽  
Author(s):  
R. J. Bawden
Keyword(s):  
Technical Assistance ◽  
Growth Potential ◽  
The Other ◽  
Adequate Diet ◽  
Female Mice ◽  
Other Hand ◽  
Australian Wool ◽  
Nematospiroides Dubius

The establishment of N. dubius juveniles was more successful in mice maintained on a diet inadequate to support the full growth potential of the animals than in mice maintained on an adequate diet. The distribution of encysted juveniles along the duodenum was considerably more extensive in the former group of mice.More juveniles were established in male than in female mice within the respective dietary groups, although the pattern of distribution was similar.The distribution of adult nematodes at 10 days after infection was confined to a smaller area of the duodenum than that of the encysted juveniles at 5 days.The differences in distribution of nematodes after 5 and 10 days between the HP and LP mice was not evident after 21 days. The survival of adult nematodes in the HP mice was more successful than in the LP animals.The female nematodes in the LP mice achieved a greater length but were less prolific egg producers than those in the HP mice.A diet inadequate to support the full growth potential of mice was therefore associated with the increased ability of Nematospiroides dubius juveniles to establish themselves in mice compared with the situation in adequately fed animals. The low plane diet, on the other hand, was associated with a decreased ability of the adult nematodes to survive.This work was supported by grants from the Commonwealth Scholarship and Fellowship Plan and the Australian Wool Board. I should like to express my appreciation for the supervision of this work by Professor J. F. A. Sprent and to thank Miss Sharon McFeeter and Mrs Anne McKeown for their most competent technical assistance.

P–060 Dose- dependent mitigation of lead acetate toxicity in males on embryo development in female mice

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Dolati ◽  
M J Zamiri ◽  
A Akhlaghi ◽  
Z Jahromi
Keyword(s):  
Adverse Effects ◽  
Embryonic Development ◽  
Embryo Development ◽  
Lead Acetate ◽  
Endocrine System ◽  
Cell Number ◽  
The Other ◽  
Control Group ◽  
Male Mice ◽  
Female Mice

Abstract Study question Does quercetin (75 or 100 mg/kg BW/day) co-administration with lead acetate to male mice affects embryonic development in female mice? Summary answer The low-dose quercetin (75 mg/kg BW/day) ameliorated the adverse effects of lead acetate on mouse embryogenesis. What is known already Lead causes male infertility by impacting on endocrine system and spermatogenesis, and may exert undesirable effects on the offspring. The currently approved treatment for lead poisoning is the use of chelating agents, which form an insoluble complex with lead and shield it from biological targets; thus, reducing its toxicity. One of the main mechanisms of lead-induced toxicity is oxidative stress, and it has been reported that natural antioxidants can reduce the heavy metals toxicity. The aim of the present study was to examine the protective effects of quercetin on the toxicity induced by lead acetate on the embryogenesis in mice. Study design, size, duration Sexually mature (eight-week-old) NMRI male mice (n = 24) were randomly divided into four groups (n = 6 per group) receiving (i) distilled water (control group); (ii) lead acetate (150 mg/kg BW/day) dissolved in deionized water (LA); (iii) lead acetate (150 mg/kg BW/day) + quercetin (75 mg/kg BW/day) (LQ75); (IV) lead acetate (150 mg/kg BW/day) + quercetin (100 mg/kg BW/day) (LQ100). Treatments were applied daily as oral gavages for one cycle of the seminiferous epithelium (35 days). Participants/materials, setting, methods At the end of treatment administration, the males were joined with super-ovulated females, and the retrieved zygotes were cultured for evaluation of the embryo development (at 2-cell, 4-cell, 8-cell, and blastocyst stages), and blastocyst cell number using differential staining (propidium iodide and bisbenzimide). After incubation of capacitated sperm with oocytes, an ultraviolet light microscope was used following 3 min incubation with 25 µg⁄mL bisbenzamide solution for fertilization assessment. Main results and the role of chance Lead acetate (LA) treatment of male mice decreased the 2-cell stage compared with the control group (P > 0.05). There was no difference between control and LQ75, and between LA and LQ100. The other stages of embryonic development were not significantly affected by the treatment. Overall, early embryonic development in the control and LQ75 mice were better than LQ100 and LA mice. The number of cells in the trophectoderm and inner-cell mass were not affected by treatments. However, the total blastocyst cell number in the control was higher than in the other groups; there was no significant difference between LQ100, LQ75 and LA groups. Fertilization rate was not affected by the treatments (P < 0.05). Quercetin acts as a potent antioxidant at low doses, but at high doses exerts a pro-oxidant action. According to previous reports, higher concentrations of quercetin increased apoptosis and necrosis while decreasing the activities of the antioxidant enzymes. Also, it has been suggested that quercetin might disrupt the endocrine system and interfere with Sertoli cell function and sperm motility. Limitations, reasons for caution A limitation of this study is narrow dose selection; more studies are needed to determine the effective dose of quercetin in ameliorating the lead toxicity. There are also side effects of lead-quercetin chelates such as metal redistribution, essential metal loss, accumulation and persistency in intracellular sites, and peroxidation. Wider implications of the findings: Lead administration adversely impacted on the embryogenesis; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on mice embryogenesis. Trial registration number Not applicable

GABAB receptor antagonism from birth to weaning permanently modifies Kiss1 expression in hypothalamus and gonads in mice

2021 ◽  
Author(s):  
Marianne Bizzozzero Hiriart ◽  
Noelia P. Di Giorgio ◽  
Carlos Libertun ◽  
Victoria A.R. Lux-Lantos
Keyword(s):  
Arcuate Nucleus ◽  
Gabab Receptor ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Hpg Axis ◽  
Estrous Cycles ◽  
Amino Butyric Acid ◽  
Periventricular Nucleus ◽  
Puberty Onset ◽  
Ovulatory Follicles

Introduction: The kisspeptin gene Kiss1 is expressed in two hypothalamic areas: anteroventral periventricular nucleus/periventricular nucleus (AVPV/PeN) and arcuate nucleus (ARC), and also in gonads. Evidences suggest that gamma-amino butyric acid B receptors (GABAB) signaling can regulate Kiss1 expression. Here we inhibited GABAB signaling from PND2-PND21 and evaluated the hypothalamic-pituitary-gonadal (HPG) axis. Methods: BALB/c mice were treated on postnatal days 2-21 (PND2-PND21) with CGP55845 (GABAB antagonist), and evaluated in PND21 and adulthood: gene expression (qPCR) in hypothalamus and gonads, hormones by radioimmunoassay, gonad histochemistry (H&E), puberty onset, estrous cycles. Results: At PND21, CGP inhibited Kiss1 and Tac2 and increased Pdyn and Gabbr1 in the ARC of both sexes and decreased Th only in female AVPV/PeN. Serum follicle-stimulating hormone (FSH) and testis weight decreased in CGP-males and puberty onset was delayed. In adults, Kiss1, Tac2, Pdyn, Pgr, Cyp19a1, Gad1 were downregulated, while Gabbr1 was upregulated in the ARC of both sexes. In the AVPV/PeN, Kiss1, Th, Cyp19a1 and Pgr decreased while Gad1 increased in CGP-females, whereas Cyp19a1 increased in CGP-males. Serum FSH increased in CGP-males while prolactin increased in CGP-females. Testosterone and progesterone increased in ovaries from CGP-females, in which Kiss1, Cyp19a1 and Esr1 were downregulated while Hsd3b2 was upregulated, together with increased atretic and decreased ovulatory follicles. Testes from CGP-males showed decreased progesterone, increased Gabbr1, Kiss1, Kiss1r, Esr2 and decreased Cyp19a1 and clear signs of seminiferous tubules atrophy. Conclusion: These results demonstrate that appropriate GABAB signaling during this critical prepubertal period is necessary for the normal development of the HPG axis.

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