4

 

 NEURAL  CONTROL  OF  GAMETOGENESIS

 

She can do this because she is sensitive to diverse cues from the environment (photoperiod, temperature, relative humidity, substrate odor, food, proximity and state of mates, etc.), is able to integrate this information in her nervous system, and via her endocrine system can use it to develop and deposit her eggs at the right time and place.

                                                                                                                                           B.S.  Heming

 

The whole process of oogenesis is regulated by the integrated control system (ICS). The process starts with neural signals from various neurotransmitter systems in response to specific external and internal stimuli. Most of these signals are conducted to gonads via the hypothalamic-pituitary-ovarian axis, but gonadal innervation also plays an important role. Within the framework of this hierarchical control system, the ovary secretes oestradiol and progesterone in a dynamic pattern that reflects the nature of transformations taking place in the ovary itself and in the reproductive system in general. These hormones play a crucial role in the activity of the granulosa and theca cells. The coordination of complex interactions between the oocyte and surrounding cell types, as well, is under neural control via the hypothalamus-pituitary-ovarian axis as well as directly via the nerves innervating the ovary. Similarly, the reproductive activity of males is under ultimate CNS control. Of crucial importance in the processes of oogenesis and spermiogenesis in metazoans is the precise synthesis and placement in gametes of cytoplasmic factors, which represent the indispensable starter and regulator of the early embryonic development.

 

Neural Control of Oogenesis in Insects and Gastropod Molluscs

 

Signal cascades for oogenesis in invertebrates originate in the CNS. In the female fire ant, Solenopsis invicta, e.g., electrical activation of the dopamine system, resulting from the processing in the brain of an external stimulus (queen pheromone), controls oogenesis and oviposition (Boulay et al., 2001). The uptake of a blood meal by the predatory bug of the Reduviidae family, Panstrongylus megistus, acts as a stimulus to which certain median neurosecretory cells of the pars intercerebralis (cells A) respond by releasing a neurohormone that stimulates proliferation of oogonia and prefollicular cells in the fifth instar up until day 6, and a neuron of another type (cells A’), which responds by stimulating secretion of ecdysone by prothoracic glands, thus determining the differentiation of ovarioles between days 16 and 24 (Heming, 2003).

Oogenesis in Drosophila is proximately regulated by the ecdysteroid hormone and JH (sesquiterpenoid juvenile hormone) (Carney and Bender, 2000). Both hormones, ecdysone and JH, are cerebrally regulated by brain signals, PTTH (prothoracicotropic hormone) (Zitnan et al., 1993) and allatotropins/allatostatins respectively. There are indications that upstream these brain signals are neurotransmitters/ neuromodulators released as a result of the processing of internal/external stimuli in neural circuits. So, e.g. a queen pheromone in colonies of Solenopsis invicta ants prevents the reproductive activity in virgin females via a neural pathway (olfactory signals are transmitted from the antennal lobe for processing in the brain). Separation of virgin ant females from the colony (this prevents the influence of the queen pheromone) for 15 days induces more than 80% increase in the dopamine level in their brain, stimulating wing shedding and reproductive activity, including ovarian development and egg laying (Boulay et al., 2001).

In Drosophila melanogaster, the development of the oocyte arrests just before vitellogenesis. The vitellogenin receptor (and its mRNA), which is essential for yolk uptake at this moment, is present and distributed throughout the oocyte. Nevertheless, endocytosis of vitellogenin into the oocyte does not start until the vitellogenin receptors increase markedly in the oocyte cortex. Vitellogenin endocytosis begins after the development of the oocyte resumes as a result of hormonal and environmental cues (Schonbaum et al., 2000). The environmental cues received via the sensory pathways are processed in the CNS and what reaches the ovary and the oocyte is not the cue itself but its neural representation, i.e. a hormonal signal (ecdysone + JH) secreted under the ultimate control of the insect CNS.

During the Drosophila oogenesis two ecdysone receptor (EcR) types are expressed in nurse cells and follicle cells, indicating that ecdysone exerts its activity in the developing oocyte via the hemolymph. EcR mutant females show oogenesis defects, including defects in the development of the egg chamber and in the vitellogenic stages.

As mentioned earlier, the oogenesis in Drosophila is regulated by ecdysone and JH (Buszczak et al., 1999). The ecdysone early response genes, E75, E74, and BR-C are expressed in stages, according to the cerebrally regulated ecdysone levels during oogenesis and the stage-specific expression of these genes regulates the egg chamber development and determines specification of the dorsal follicle cell fates (Buszczak et al., 1999).

In molluscs reproduction is seasonally regulated in response to environmental stimuli, with the photoperiod being the most important cue. The neuronal structures for processing these reproductive stimuli in mollusks

 

are diffusely located in the brain and the neuroendocrine circuitry is highly complex. (Wayne, 2001)

 

The central nervous system in molluscs comprises varied numbers of ganglia, each of them composed of thousands of neurons.

 

When continually kept under laboratory short day conditions males and females of the slug Limax maximus remain sexually immature, but they develop the mature reproductive tract and produce mature gametes soon after they are transferred under long day conditions. Transplantation of the ganglia of long day-stimulated slugs into the immature short day-inhibited slugs induced the development of the mature reproductive tract whereas transplantation of short day ganglia did not induce the development of the reproductive tract (Wayne, 2001). Under the influence of stimulating long days, the slug brain secretes a maturation-inducing hormone (MH), which induces the synthesis of one or more hormones by the gonads (figures 4.1 and 4.2). Implantation of the brains of long day-stimulated slugs into the brains of short day-inhibited slugs, even under short day conditions, stimulates development of gonads and accessory sex organs in the latter (McCrone and Sokolove, 1986).

Biologists have known for some time that in many invertebrates hormones, as mediators of neural signals, regulate the ovulation and the number of eggs to be deposited, but recently it has been reported that in the snail, Helix aspersa, a branch of the intestinal nerve rather than hormones is immediately responsible for that regulation (Antkowiak and Chase, 2003; figure 4.3).. These experiments suggest that photoperiod activates neurons in the brain that, in turn, activate the gonad, thereby stimulating maturation of the accessory sex organs.

 

Figure 4.1. (a) Effects of photoperiod and brain transplants on the reproductive system of Limax maximus.  Brains transplanted from donor slugs maintained on stimulatory long days stimulated the reproductive system in recipient slugs maintained on inhibitory short days. Brains from short-day animals had no effect on maturation of the reproductive system. These findings indicate that the brain mediates the effects of photoperiod on maturation of the reproductive system.

(b) Effects of brain and gonad transplants on the reproductive system of Limax. Transfer of gonadectomized slugs from inhibitory short days to stimulatory long days had no effect on maturation of the accessory sex organs, indicating that secretions from the gonad are important for mediating the effect of photoperiod on this aspect of the maturation process. Transplanting gonads from slugs maintained on long days to gonadectomized animals stimulated maturation of the accessory sex organs. Likewise, transplanting brains from long-day

(c) A model for photoperiodic stimulation of the reproductive system of Limax. Long photoperiods stimulate unknown photoreceptors, activating neurons in the cerebral ganglion to secrete a hermaphroditic maturation factor and male gonadotropic factor. These secretions from the cerebral ganglion stimulate the gonad to release additional hormones that stimulate maturation of the female and male accessory sex organs (From Wayne, 2001).

 

 

 

Figure 4.2. (a) Organization of the female reproductive endocrine system of Lymnaea stagnalis. Neurons in the lateral lobes activate the endocrine dorsal bodies and caudodorsal cells. Dorsal body hormone, secreted from the lateral and medial dorsal bodies, stimulates vitellogenesis and growth and differentiation of the female accessory sex organs. Caudodorsal cell hormone secreted by the caudodorsal cells, stimulates ovulation and egg-laying behaviors.

 (b) Organization of the female reproductive system of Aplysia californica. Signals from neurons in the cerebral ganglia are transmitted to the pleural ganglia and then to the bag cell neurons located at the junction between the abdominal ganglion and pleurovisceral connective nerves. This electrical input from higher-order centers activates a long-lasting afterdischarge (typically 10-30 min in duration). The afterdischarge triggers secretion of egg-laying hormone (ELH), which then stimulates ovulation and egg-laying behaviors.

(c) Temperature sensitivity of the Aplysia reproductive axis, influencing ovulation and egg-laying behavior. Studies show that temperature has no significant effect on responsiveness of the ovotestis to ELH stimulation, has some effects on bag-cell neuron functions, and has a robust effect on responsiveness of the head ganglia to stimulation. Temperature’s effects on ovulation and egg-laying behavior is primarily through changes in excitability of the head ganglia, ultimately controlling whether or not the bag-cell neurons will afterdischarge. The direct effects of temperature on bag-cell excitability and ELH secretion are variable and less robust, suggesting that temperature-induced changes in responsiveness of the bag cell neurons play a secondary role.

Abbreviations: LDB, lateral dorsal body; LL, lateral lobe; MDB, medial dorsal body; CDC, caudodorsal cells; CDCH, caudodorsal cell hormone; DBH, dorsal body hormone; ELH, egg-laying hormone (From Wayne, 2001).

 

 

gland; HD, hermaphroditic duct; LCe, left cerebral ganglion; OT, ovotestis; P, proximal; RCe, right cerebral ganglion; RPa, right parietal ganglion; SV, seminal vesicle; V, visceral ganglion (From Antkowiak and Chase, 2003).

 

This brief review of the production of egg cells in insects and gastropod mollusks shows that it results from a complex process involving numerous systems and pathways, all of which point to the controlling role of the CNS in the process. Taking as an example the production of the egg cell by a female insect, Bruce S. Heming described the essence of the oogenesis as follows:

 

She can do this because she is sensitive to diverse cues from the environment (photoperiod, temperature, relative humidity, substrate odor, food, proximity and state of mates, etc.), is able to integrate this information in her nervous system, and via her endocrine system can use it to develop and deposit her eggs at the right time and place. (Heming, 2003)

 

 

Neural Control of Oogenesis in

Vertebrates

 

Neuroendocrine Control via the Brain-Hypothalamic-Pituitary Axis

 

In vertebrates, oogenesis is under control of signal cascades that start in the CNS, with the hypothalamus-pituitary-ovarian axis (hypothalamic GnRH à pituitary FSH à estrogen and progesterone) as the main neuroendocrine axis that regulates the egg cell development, ovulation like all the rest of the physiological, behavioral, and morphological changes related to the reproductive activity. Oogenesis and ovulation, in both ovulation-inducible vertebrates such as rabbits (Strand, 1999g) and cyclic ovulators such as humans (Johnson and Crowley, 1986; Villa-Diaz and Barrel, 1999) are under neural control (Adler and Crowley, 1984; Kalra et al., 1987; Gore and Terasawa, 2001).

So, e.g., even though resumption of meiosis requires progesterone, which is secreted by the follicle cells in response to pituitary gonadotropins (Gilbert, 1997b), the latter is secreted in response to brain signals, i.e., from hypothalamic GnRH (gonadotropin-releasing hormone) secreted by the hypothalamic GnRH neurons in response to other neurosignals from a number of brain centers.

In fish, the neurohormonal control of oocyte growth and maturation is mediated respectively by estradiol-17 beta and -17 alpha, 20 beta-DP (17-alpha,20-beta-dihydroxy-4-pregnen-3- one) that are synthesized in granulosa cells by steroid precursors provided by theca cells. The latter is the naturally maturation-inducing hormone in the medaka fish. A variety of other neuromodulatory factors are involved in steroidogenesis in fish ovarian follicles (Fukada et al., 1994; Nagahama et al., 1995).

In sheep it has been demonstrated that granulosa cells, in response to FSH stimulation start production of inhibin A (Campbell and Baird, 2001; Drummond et al., 2000). Inhibin production seems to be downregulated by follicle synthesis of estrogen (Drummond et al., 2000), but it has endocrine effects on the pituitary FSH. In humans, paracrine IGFs (insulin-like growth factors) are involved in the synthesis of inhibin A and B, but the main regulators of their production are gonadotropin hormones, FSH and LH, via protein kinase A signal transduction pathway (Vanttinen et al., 2000). As it is well known, gonadotropins themselves are under the control of CNS signals.

The synthesis of progesterone by the granulosa cells is stimulated by various hormones and growth factors, with gonadotropins and IGF1 (inslulin-like growth factor 1) as the most important ones (Khamsi and Roberge, 2001). The immediate effect of neurohormones on progesterone secretion, as well as the fact that gonadotropins and IGF-1 are under neuroendocrine control (hypothalamic GHRH à pituitary GH à IGF-1), shows that progesterone secretion is a downstream element of a signal cascade that starts with an electrical/chemical output of the neural circuits in the CNS. Experiments on rat granulosa cells have also demonstrated the stimulating effect of adrenergic agents on progesterone secretion (Selvaraj et al., 2000).

Another growth factor, interleukin-6, inhibits expression of the LHR (luteinizing hormone receptor) in granulosa cells, which may have a role in the maturation of ovarian follicles (Tamura et al., 2001). It is also found to be involved in the regulation of oocyte maturation by inhibiting secretion of estradiol (E2) and the FSH-stimulated progesterone (Salmassi et al., 2000).

 

 

Local Control by Ovarian Innervation

 

In vertebrates, the innervation of the ovary by superior ovarian nerve, vagus, and the ovarian plexus stimulatorily regulates the effects of hCG.......................................