1. Gamete and Zygote Transport
Chapter 30
Gamete and Zygote Transport
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

2. FIGURE 30.1 This figure is reproduced in color in the color plate section. (A) Schematic representation of the head of a mouse embryo at E14.5, showing the scaffold of vomeronasal/terminal nerve fibers (thick lines) along which GnRH cells (neuron-like shapes) migrate from the nose to the brain. (B) Sagittal section of the rostral and ventral forebrain regions at E14.5, immunolabeled for GnRH. Arrows show GnRH neuronal cell bodies. (C, D) Coronal section of the preoptic region showing GnRH neuroendocrine cells (arrows, C) and their nerve terminals in the median eminence (me, D) in newborn (P0) mice. In D, the inset shows a higher magnification of the area identified by the arrow in the main panel. Abbreviations: oe, olfactory epithelium; vno, vomeronasal organ; nm, frontonasal mesenchyme; mob, main olfactory bulb; aob, accessory olfactory bulb; vfb, ventral forebrain; cx, cerebral cortex; ovlt, organum vasculosum of the lamina terminalis; 3V, third ventricle. Scale bar: 100 μm (50 μm in inset).
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

3. FIGURE 30.2 Centrally driven gonad-independent and gonad-dependent activation of the female HPG axis. (Hypothalamic development) Although the morphological development of the hypothalamic site (the AVPV) known to mediate the positive-feedback effect of estradiol (E2) onto GnRH neurons (ovals) in sexually mature female individuals is complete at birth, axons of the ARH neurons, which are suspected of play- ing a key role in mediating the estrogen negative feedback, first reach the preoptic region during the infantile period. Mature projections are established by postnatal day 16 (P16). (Hormonal profiles) Schematic diagrams illustrating our present understanding of centrally driven gonad- independent and gonad-dependent changes in hormonal profiles during female postnatal development. (Ovarian maturation) Schematic diagram illustrating how the aforementioned changes affect folliculogenesis, and conversely, how the advancement of follicular maturation modulates hypothalamic/pituitary function through E2 secretion during postnatal development. AVPV, anteroventral periventricular nucleus; ARH, arcu- ate nucleus of the hypothalamus; DMH, dorsomedial nucleus of the hypothalamus; LHA, lateral hypothalamic area; MEPO, median preoptic nucleus; MPN, medial preoptic nucleus; PVH, paraventricular nucleus.
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

4. FIGURE 30. 3 Postnatal maturation of the male HPG axis
FIGURE 30.3 Postnatal maturation of the male HPG axis. (Hypothalamic development) As in females, although development of the sexually dimorphic AVPV is complete at birth and its masculinization via gonad-dependent mechanisms occurs during the neonatal period, ARH projec- tions to the preoptic region develop and mature during the infantile period. In the male, GnRH neurons (ovals) are subjected to extensive pruning of their dendrites and changes in dendritic spine density during postnatal development; although GABAergic inputs to GnRH neurons do not appear to change, glutamatergic afferents are thought to increase dramatically between the infantile period and adulthood. (Hormonal profiles) Schematic diagrams illustrating our present understanding of centrally driven (and likely gonad-independent changes in hormonal profiles dur- ing male postnatal development). (Testicular maturation) Schematic diagram illustrating how the aforementioned changes affect spermatogenesis and Leydig cell function in the testes. Glu, glutamate; AVPV, anteroventral periventricular nucleus; ARH, arcuate nucleus of the hypothalamus; DMH, dorsomedial nucleus of the hypothalamus; LHA, lateral hypothalamic area; MEPO, median preoptic nucleus; MPN, medial preoptic nucleus; PVH, paraventricular nucleus.
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

5. FIGURE 30.4 Schematic diagram illustrating the different maturational steps leading to the onset of puberty in females and their putative neural control during postnatal development. The projection of ARH neurons to the preoptic region during the infantile period and the maturation of the synaptic contacts they establish may constitute the first centrally driven gonad-independent trigger for sexual maturation, by prompting the infantile FSH surge and thereby initiating the growth of the follicles that will ovulate at puberty. Subse- quently, with the gradual decrease in circulating levels of alpha-fetoprotein, the low estradiol (E2) levels produced by growing follicles pro- gressively gain access to the hypothalamus, where they exert a negative-feedback effect on ARH neurons. Besides, neurons and glial cells from the tuberal and preoptic regions of the hypothalamus, and possibly also neurons from other brain areas, contribute to the maturation of the pattern of pulsatile LH secretion throughout the juvenile and peripubertal periods, further promoting follicular growth. When ovar- ian follicles reach the Graafian stage, the increasing amount of E2 they produce exerts a positive-feedback effect on the neurons of the AVPV, which coordinate the onset of the first preovulatory GnRH and LH/FSH surge, thus triggering the first ovulation and conferring fertility on the individuals. PGE2, prostaglandin E2; AVPV, anteroventral periventricular nucleus; ARH, arcuate nucleus of the hypothalamus; PMv, ventral premammillary nucleus.
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition

6. FIGURE 30.5 There is now a growing body of evidence to indicate that, concurrently with the transsynaptic regulatory mechanisms illus- trated in Figure 30.4, cell–cell interactions involving nonneuronal cells such as astrocytes are also of critical importance for the regulation of GnRH secretion. Indeed, in the hypothalamus, as in most areas of the central nervous system, the classic one-way dialogue at the chemical synapse that forms the functional unit for the transmission of information between a nerve terminal and its target is being reevaluated on the strength of recent demonstrations that glial cells, the presumed electrically silent cohabitants of the nervous system, might be a critical third element of the synapse. 431,432,598–602 The present schematic diagram depicts one example of a mechanism by which hypothalamic astrocytes may contribute to the maturation of the GnRH neural network during postnatal development via the release of a gliotransmitter, prostaglandin E2 (PGE2), that not only potently stimulates the electrical activity of GnRH neurons, 603 but also modulates spine density in hypothalamic neurons. 590 Experimental studies have suggested that neuronally released glutamate (Glu) (1) coactivates metabotropic glutamatergic (mGluR) and AMPA glutamatergic receptors (GluR) in astrocytes, (2) stimulating the activity of zinc-dependent matrix metalloproteinases (MMPs) of the ADAM (a disintegrin and metalloproteinase) family, and (3) the MMPs catalyze ectodomain shedding by the pro-EGF ligands pro-TGFα and pro-NRG (proneuregulin). In particular, the processing of pro-TGFα has been shown to involve the metalloproteinase ADAM17, also known as tumor necrosis factor α converting enzyme (TACE). The subsequently released mature TGFα and NRG activate ERBB1/ERBB2 and ERBB4/ERBB2 heterodimers, respectively. 604 The co-activation of glutamatergic receptors induces the recruitment of ERBB1, ERBB4, and their pro-ligands to the cell membrane, where multiprotein complexes form, as demonstrated by the direct physical association of glutamatergic and erbB receptors (not shown). The activation of ERBB receptors in hypothalamic astrocytes promotes profound morphological changes, including cytoplasmic retraction and the elongation and stellation of processes 605 (4’). The activation of ERBB receptors also promotes the release of PGE 2595,604,606 (4), which stimulates a cAMP/protein kinase A (PKA) pathway in GnRH neurons through the mobilization of EP2 receptors (EP2-R) 603 (5). The activation of this signaling pathway induces a reversible membrane depolarization of GnRH neurons leading to the initiation of spike firing via a postsynaptic effect involving the activation of a nonselective cation current 603 (6). The perception of synaptically released glutamate, GABA, or both, 607 by astrocytes, may contribute to the increase in hypothalamic GnRH feed-forward signaling in developing mice and rats. Indeed, the selective alteration of only one of these signaling components in astrocytes, such as ERBB4, hampers spontaneous GnRH neuronal activity 603 and delays puberty onset. 259
© 2015, Elsevier, Inc., Plant and Zeleznik, Knobil and Neill's Physiology of Reproduction, Fourth Edition