Impact of Proestrus on Gene Expression in the Medial Preoptic Area of Mice

Abstract

The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have been recognized as gonadal hormone receptive regions of the rodent brain that—via wiring to gonadotropin-releasing hormone (GnRH) neurons—contribute to orchestration of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction of GnRH surge show altered expression in proestrus. Therefore, we compared the expression of 48 genes obtained from intact proestrous and metestrous mice, respectively, by quantitative real-time PCR (qPCR) method. Differential expression of 24 genes reached significance (p < 0.05). Genes upregulated in proestrus encoded neuropeptides (kisspeptin (KP), galanin (GAL), neurotensin (NT), cholecystokinin (CCK)), hormone receptors (growth hormone secretagogue receptor, μ-opioid receptor), gonadal steroid receptors (estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR)), solute carrier family proteins (vesicular glutamate transporter 2, vesicular monoamine transporter 2), proteins of transmitter synthesis (tyrosine hydroxylase (TH)) and transmitter receptor subunit (AMPA4), and other proteins (uncoupling protein 2, nuclear receptor related 1 protein). Proestrus evoked a marked downregulation of genes coding for adenosine A2a receptor, vesicular gamma-aminobutyric acid (GABA) transporter, 4-aminobutyrate aminotransferase, tachykinin precursor 1, NT receptor 3, arginine vasopressin receptor 1A, cannabinoid receptor 1, ephrin receptor A3 and aldehyde dehydrogenase 1 family, member L1. Immunocytochemistry was used to visualize the proteins encoded by Kiss1, Gal, Cck and Th genes in neuronal subsets of the AVPV/MPOA of the proestrous mice. The results indicate that gene expression of the AVPV/MPOA is significantly modified at late proestrus including genes that code for neuropeptides, gonadal steroid hormone receptors and synaptic vesicle transporters. These events support cellular and neuronal network requirements of the positive estradiol feedback action and contribute to preparation of the GnRH neuron system for the pre-ovulatory surge release.

Reorganization of perineuronal nets in the medial Preoptic Area during the reproductive cycle in female rats

“…In addition to its key role in the expression of parental and sexual behavior [38][39][40] , the mPOA is involved in neuroendocrine functions as the secretion of gonadotropin-releasing hormone, among other endocrine mediators 41 . As pointed out by Horii-Hayashi et al, in cycling females the mPOA would require high levels of neural plasticity, both structurally and synaptically, to adequately respond to the hormonal levels in the circulation, a fact that might explain the absence of PNNs 26 .…”

Estradiol Increases Glutamate and GABA Neurotransmission into GnRH Neurons via Retrograde NO-Signaling in Proestrous Mice during the Positive Estradiol Feedback Period

“…Earlier studies have demonstrated that kisspeptin neuron populations of the AVPV region and the kisspeptin/neurokininB/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) mediate the positive and negative feedback actions of E2 toward the GnRH system ( Smith et al, 2005 ; Kalló et al, 2012 ; Clarkson et al, 2017 ; Lunenfeld and Buhler, 2017 ; Vastagh and Liposits, 2017 ). Human mutations and knock out animals clearly showed the importance of these indirect pathways in the feedback regulation of GnRH neurons ( Mayer and Boehm, 2011 ; Brioude et al, 2013 ; Ratnasabapathy and Dhillo, 2013 ; Demirbilek et al, 2015 ).…”

Social Behavior: How the Brain Thinks like a Mom

“…In the last century, lesion experiments revealed that neural activity located in the medial preoptic area (MPOA) region of the hypothalamus is crucial to initiate parental care [6,7]. This area of the brain is composed of a variety of neuron types each expressing different neurotransmitters, neuropeptides, and receptors [8], yet only a subset is likely to promote parenting because the MPOA is also required to drive other innate behaviors including thermoregulation [9], sleep [10], and courtship behavior [11]. More recently, Catherine Dulac and colleagues identified one of these MPOA neural subsets that is distinguished by their expression of the neuropeptide galanin (MPOA Gal ) [12].…”

“…This is in contrast to the prefrontal cortex (PFC), where neurons show a high degree of mixed selectivity [4], such that identifying perceptual content has proved to be more challenging. As such, despite ample evidence that PFC activity underlies subjective judgments in perceptual tasks [5,6], the causal status of PFC activity for consciousness is debated [7,8].…”