Mapping <scp>GABA</scp> and glutamate inputs to gonadotrophin‐releasing hormone neurones in male and female mice

Moore, Aleisha M.; Abbott, Georgina; Mair, Jonathan; Prescott, Melanie; Campbell, Rebecca E.

doi:10.1111/jne.12657

Cited by 23 publications

(24 citation statements)

References 55 publications

(125 reference statements)

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“…AAs, as one of major pathways of function, can be transformed into metabolites such as gamma-aminobutyric acid (GABA) [56], nitric oxide (NO) [57], dopamine [58], and serotonin (5-HT) [59]. The ability of GABA to modulate GnRH secretion has been proven in sheep [60] and mice [61], and its role in driving ovulation has been confirmed [62]. Furthermore, NO, an important metabolite, can affect GnRH release [63].…”

Section: Discussionmentioning

confidence: 99%

Comparative Transcriptomics Reveal Key Sheep (Ovis aries) Hypothalamus LncRNAs that Affect Reproduction

Zhang

Tang

et al. 2019

Animals

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The diverse functions of long noncoding RNAs (lncRNAs), which execute their functions mainly through modulating the activities of their target genes, have been have been widely studied for many years (including a number of studies involving lncRNAs in the ovary and uterus). Herein, for the first time, we detect lncRNAs in sheep hypothalami with FecB++ through RNA Sequencing (RNA-Seq) and identify a number of known and novel lncRNAs, with 622 and 809 found to be differentially expressed in polytocous sheep in the follicular phase (PF) vs. monotocous sheep in the follicular phase (MF) and polytocous sheep in the luteal phase (PL) vs. monotocous sheep in the luteal phase (ML), respectively. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed based on the predicted target genes. The most highly enriched GO terms (at the molecular function level) included carbonyl reductase (NADPH), 15-hydroxyprostaglandin dehydrogenase (NADP+), and prostaglandin-E2 9-reductase activity in PF vs. MF, and phosphatidylinositol-3,5-bisphosphate binding in PL vs. ML was associated with sheep fecundity. Interestingly, the phenomena of valine, leucine, and isoleucine degradation in PL vs. ML, and valine, leucine, and isoleucine biosynthesis in PF vs. MF, were present. In addition, the interactome of lncRNA and its targets showed that MSTRG.26777 and its cis-targets ENSOARG00000013744, ENSOARG00000013700, and ENSOARG00000013777, and MSTRG.105228 and its target WNT7A may participate in the sheep reproductive process at the hypothalamus level. Significantly, MSTRG.95128 and its cis-target Forkhead box L1 (FOXG1) were shown to be upregulated in PF vs. MF but downregulated in PL vs. ML. All of these results may be attributed to discoveries of new candidate genes and pathways related to sheep reproduction, and they may provide new views for understanding sheep reproduction without the effects of the FecB mutation.

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Section: Discussionmentioning

confidence: 99%

Comparative Transcriptomics Reveal Key Sheep (Ovis aries) Hypothalamus LncRNAs that Affect Reproduction

Zhang

Tang

et al. 2019

Animals

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“…Perfusion fixed brains were saturated in 30% sucrose-Tris buffer saline (TBS) and cut into three or four series of 30-μm thick coronal sections using a freezing stage microtome (Leica®, Wetzlar, Germany). The brain tissue of every experimental animal was subjected to standard single or double immunofluorescent labelling as detailed previously [36] to assess transfection levels and probe or cannula placement.…”

Section: In Vivo Chemogenetic Activation Protocolsmentioning

confidence: 99%

Activation of arcuate nucleus GABA neurons promotes luteinizing hormone secretion and reproductive dysfunction: Implications for polycystic ovary syndrome

Silva¹,

Desroziers²,

Hessler

et al. 2019

eBioMedicine

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Background Enhanced GABA activity in the brain and a hyperactive hypothalamic-pituitary-gonadal axis are associated with polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Women with PCOS exhibit elevated cerebrospinal fluid GABA levels and preclinical models of PCOS exhibit increased GABAergic input to GnRH neurons, the central regulators of reproduction. The arcuate nucleus (ARN) is postulated as the anatomical origin of elevated GABAergic innervation; however, the functional role of this circuit is undefined. Methods We employed a combination of targeted optogenetic and chemogenetic approaches to assess the impact of acute and chronic ARN GABA neuron activation. Selective acute activation of ARN GABA neurons and their fiber projections was coupled with serial blood sampling for luteinizing hormone secretion in anesthetized male, female and prenatally androgenised (PNA) mice modelling PCOS. In addition, GnRH neuron responses to ARN GABA fiber stimulation were recorded in ex vivo brain slices. Chronic activation of ARN GABA neurons in healthy female mice was coupled with reproductive phenotyping for PCOS-like features. Findings Acute stimulation of ARN GABA fibers adjacent to GnRH neurons resulted in a significant and long-lasting increase in LH secretion in male and female mice. The amplitude of this response was blunted in PNA mice, which also exhibited a blunted LH response to GnRH administration. Infrequent and variable GABA A -dependent changes in GnRH neuron firing were observed in brain slices. Chronic activation of ARN GABA neurons in healthy females impaired estrous cyclicity, decreased corpora lutea number and increased circulating testosterone levels. Interpretation ARN GABA neurons can stimulate the hypothalamic-pituitary axis and chronic activation of ARN GABA neurons can mimic the reproductive deficits of PCOS in healthy females. Unexpectedly blunted HPG axis responses in PNA mice may reflect a history of high frequency GnRH/LH secretion and reduced LH stores, but also raise questions about impaired function within the ARN GABA population and the involvement of other circuits.

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“…FSH and LH then co-activate the ovarian secretion of 17β-estradiol (E 2 ) and progesterone (P 4 ) via their receptors in the granulosa cells or luteal cells (Albritton, 1941; Nalbandov and Card, 1946; Liu et al., 2018), while the secretion and release of GnRH to the pituitary portal system can be induced and controlled through stimuli received from other mediators in different regions of cerebrum. Diverse mediators such as central neurotransmitters and neuropeptides are integrated in the hypothalamus to regulate the reproductive system (Moore et al., 2018; Saedi et al., 2018). Neurotransmitters of norepinephrine (NE) and prostaglandin E 2 (PGE 2 ), which regulated the activity of neurons in hypothalamus, are potential stimulators affecting the hypothalamic GnRH release (Zwain et al., 2002; Sharif et al., 2013; Fujioka et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

Electro-Acupuncture Affects the Activity of the Hypothalamic-Pituitary-Ovary Axis in Female Rats

et al. 2019

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Hypothalamic-pituitary-ovary (HPO) axis is a dominant system controlling ovulation during puberty. Electro-acupuncture (EA) has been widely used to cure the reproductive diseases associated with endocrinological disorders. However, whether EA treatment affects HPO axis activity of physiological animals and induces alterations on the hormones in the HPO axis was also unclear. Here, we performed the EA stimuli on bilateral acupoints of Sanyinjiao (SP6) and Zusanli (ST36) on female virgin rats every 3 days and for a total of 5 times. The results showed that GnRH levels in hypothalamus were greatly upregulated in EA-treated rats than untreated animals at day 7 and 13. The serum levels for FSH and LH were severely reduced after EA treatment compared with EA-untreated animals at day 1, while they were greatly increased at day 7 and 13. The serum concentrations of 17β-estradiol were lower in EA-treated rats versus untreated animals at day 7, while they were higher in EA-treated rats than other groups at day 13. However, the progesterone concentrations were lower in EA-treated rats than Control and Sham-EA rats both at day 7 and 13. More importantly, we found that the prostaglandin E 2 level in serum was reduced in EA-treated rats versus untreated rats at day 1, while they were upregulated at day 7 and 13. Conversely, the norepinephrine level in serum was increased at day 1, while they were decreased greatly in EA-treated rats versus untreated rats at day 7 and 13. The current results demonstrated that EA could modulate homeostasis of HPO axis in physiologic rats, which would be useful to clarify the mechanisms of EA application on pathological and physiological animals or human.

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Mapping GABA and glutamate inputs to gonadotrophin‐releasing hormone neurones in male and female mice

Cited by 23 publications

References 55 publications

Comparative Transcriptomics Reveal Key Sheep (Ovis aries) Hypothalamus LncRNAs that Affect Reproduction

Comparative Transcriptomics Reveal Key Sheep (Ovis aries) Hypothalamus LncRNAs that Affect Reproduction

Activation of arcuate nucleus GABA neurons promotes luteinizing hormone secretion and reproductive dysfunction: Implications for polycystic ovary syndrome

Electro-Acupuncture Affects the Activity of the Hypothalamic-Pituitary-Ovary Axis in Female Rats

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