Département d'Obstétrique-Gynécologie, Faculté de Médecine, Université de Montréal and Centre de Recherche, Centre Hospitalier de l'Université de Montréal (CHUM)-Hôpital Saint-Luc, Montréal, Québec, Canada.
Life Sciences (Impact Factor: 2.7). 01/2008; 81(25-26):1627-37. DOI: 10.1016/j.lfs.2007.09.034
The involvement of neurotransmitters in mammalian female reproductive tissues has been the object of several studies in past decades. This review focuses on new evidence that serotonin (or 5-hydroxytryptamine, 5-HT) may be an important key player, acting locally in mammalian ovaries and female genital tracts where it may influence granulosa and cumulus cells as well as oocytes and early embryos. Pioneering studies reporting 5-HT in ovaries and other female reproductive tissues and cells are now complemented by the identification of specific 5-HT receptor subtypes (5-HT(1D), 5-HT(2A-B) and 5-HT(7)) in granulosa or cumulus cells, oocytes and early embryos. Additional serotonergic players, including the 5-HT transporter (SERT or Slc6A4) expressed in oocytes and embryos, and the 5-HT-producing enzyme tryptophan hydroxylase-1 (TPH1) expressed in cumulus cells, now make up a complete and autonomous local serotonergic network. Direct demonstrations of intracellular Ca(2+) and cAMP signaling by 5-HT in cumulus cells and its capacity to regulate progesterone secretion by granulosa cells further illustrate some of its potential functions in ovarian physiology. Recent evidence shows that mouse mothers with knocked-out TPH1 have embryos with impaired early development, establishing that maternal 5-HT is required for normal embryonic development. This local regulation of reproductive processes by 5-HT in mammals might have derived from better-known, and possibly ancestral, serotonergic networks similarly at play in several primitive animals, and potential implications for human reproduction may also be foreseen. Specific roles played by 5-HT in mammalian reproduction remain to be further investigated, and now span from steroidogenesis and oocyte maturation to early embryonic development.
"The hypothesis that 5-HT plays a critical role as growth regulatory signal in the developing brain [3,9,10] was confirmed by subsequent studies [8,11]. In addition to its role in neuronal development, 5-HT is implicated in regulation of various developmental processes, i.e., meiosis reinitiating, cell divisions, morphogenetic movements, and left-right axis patterning [4-6,12-15]. "
[Show abstract][Hide abstract] ABSTRACT: Serotonin (5-HT) is well known as widely distributed modulator of developmental processes in both vertebrates and invertebrates. It is also the earliest neurotransmitter to appear during neuronal development. In aquatic invertebrates, which have larvae in their life cycle, 5-HT is involved in regulation of stages transition including larval metamorphosis and settlement. However, molecular and cellular mechanisms underlying developmental transition in aquatic invertebrate species are yet poorly understood. Earlier we demonstrated that in larvae of freshwater molluscs and marine polychaetes, endogenous 5-HT released from the neurons of the apical sensory organ (ASO) in response to external stimuli retarded larval development at premetamorphic stages, and accelerated it at metamorphic stages. Here we used a freshwater snail Helisoma trivolvis to study molecular mechanisms underlying these dual developmental effects of 5-HT.
Larval development of H. trivolvis includes transition from premetamorphic to metamorphic stages and shares the main features of metamorphosis with free-swimming aquatic larvae. Three types of 5-HT receptors (5-HT1-, 5-HT4- and 5-HT7-like) are functionally active at premetamorphic (trochophore, veliger) and metamorphic (veliconcha) stages, and expression patterns of these receptors and respective G proteins undergo coordinated changes during development. Stimulation of these receptors modulated cAMP-dependent regulation of cell divisions. Expression of 5-HT4- and 5-HT7-like receptors and their downstream Gs protein was down-regulated during the transition of pre- to metamorphic stage, while expression of 5-HT1 -like receptor and its downstream Gi protein was upregulated. In accordance with relative amount of these receptors, stimulation of 5-HTRs at premetamorphic stages induces developmental retardation, while their stimulation at metamorphic stages induces developmental acceleration.
We present a novel molecular mechanism that underlies stage-specific changes in developmental tempo of H. trivolvis larvae in response to endogenous 5-HT produced by the neurons of the ASO. We suggest that consecutive changes in expression patterns of different receptors and their downstream partners in the course of larval development represent the molecular base of larval transition from premetamorphic (non-competent) to metamorphic (competent) state.
"Anatomical studies have shown that in the hypothalamus, the GnRH-producing neurons receive innervation by the serotoninergic system (Smith and Jennes 2001), which modulates GnRH secretion. Different studies have confirmed the presence of serotonin in the hypophysis (Westlund and Childs 1982; Payette et al. 1985; Carvajal et al. 1991; Vanhatalo and Soinila 1995) and the gonads (Veselá et al. 2003; Dubé and Amireault 2007). In the ovary, several elements of the serotoninergic system are present (Veselá et al. 2003; Amireault and Dubé 2005a, 2005b). "
[Show abstract][Hide abstract] ABSTRACT: To elucidate the role of serotonin in the onset of puberty, the effects of both systemic and in-ovarian bursa administration of serotonin on the neuroendocrine mechanism that modulates the onset of puberty, follicular development and first ovulation were evaluated. Two experiments were carried out. For the first, 25 or 37.5mgkg-1 of bodyweight of serotonin creatinine sulfate was administered by a subcutaneous route to 30-day-old female rats. In the second experiment, serotonin creatinine sulfate was administered directly into the ovarian bursa of 34-day-old female rats. Systemic administration of 25 or 37.5mgkg-1 of serotonin creatinine sulfate induced a delay in the ages of vaginal opening and first vaginal oestrus, a decrease in the number of ovulating animals, and serum concentrations of FSH, LH, oestradiol and progesterone. An increase in the number of Class 3 (>500m) and atretic follicles was observed in the ovaries of these animals. The administration of serotonin creatinine sulfate in the ovarian bursa did not modify the onset of puberty and ovulation, but a reduced serum concentration of oestradiol was observed. Our results suggest that serotonin acts on the components of the hypothalamus-hypophysis- ovary axis by modulating follicular development, ovarian functions and the onset of puberty.
Reproduction Fertility and Development 11/2012; 25(8). DOI:10.1071/RD12253 · 2.40 Impact Factor
"Multiple lines of evidence suggest that serotonin (5- hydroxytryptamine, 5-HT) plays an important role in the early development of neural and non-neural tissues of both vertebrate and invertebrate species (Hansson et al., 1999; Herlenius and Lagercrantz, 2001; Gaspar et al., 2003; Vitalis and Parnavelas, 2003; Li, 2006; Dubé and Amireault, 2007). The monoamine is already detected in the fertilized egg and, prior to the time that it assumes its role as a neurotransmitter, 5-HT is involved in the early morphogenesis of the heart, the cranial mesenchyme, the notochord, neural crest derivatives , and the brain (Shuey et al., 1992; Hansson et al., 1999). "
[Show abstract][Hide abstract] ABSTRACT: A Cre/loxP-based fate mapping approach was used to follow the regions of the mouse thyroid labeled by the serotonin transporter SERT. Reporter gene expression (lacZ) is activated by Cre expression from the SERT locus in SERT(Cre/+) ;ROSA26R compound mouse embryos. Cell labeling, first detected in the thyroid primordium at the E10.5 prenatal stage, was followed until the postnatal day P30. The co-localization of lacZ staining in the same cells that express the transcription factors Nkx2.1 and Pax8 at the E12.5 stage confirms their identity as thyroid cell precursors. SERT immunohistochemistry on thyroid sections of E18.5 embryos showed SERT expression in thyroid follicular cells. Western blotting analysis confirmed the expression of the protein in adult thyroid tissue and cultured FRTL-5 cells. These results describe the fate of SERT-expressing cells during thyroid development, suggesting an active role of SERT in the development and functions of mammalian thyroid. They also highlight the possibility to use the SERT-Cre mouse line as a good Cre driver in early thyroid development.
The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 03/2011; 294(3):384-90. DOI:10.1002/ar.21353 · 1.54 Impact Factor
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