Skip to main content
SpringerLink
Log in

Ovarian innervation develops before initiation of folliculogenesis in the rat

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

Sympathetic neurotransmitters have been shown to be present in the ovary of the rat during early postnatal development and to affect steroidogenesis before the ovary becomes responsive to gonadotropins, and before the first primordial follicles are formed. This study was undertaken to determine if development of the ovarian innervation is an event that antedates the initiation of folliculogenesis in the rat, Rattus norvegicus. Serial sections of postnatal ovaries revealed a negligible frequency of follicles 24 h after birth (about 1 primordial follicle per ovary). Twelve hours later there were about 500 follicles per ovary, a number that more than doubled to about 1300 during the subsequent 12 h, indicating that an explosive period of follicular differentiation occurs between the end of postnatal days 1 and 2. Electron microscopy demonstrated that before birth the ovaries are already innervated by fibers containing clear and dense-core vesicles. Immunohistochemistry performed on either fetal (day 19) or newborn (less than 15h after birth) ovaries showed the presence of catecholaminergic nerves, identified by their content of immunoreactive tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. While some of these fibers innervate blood vessels, others are associated with primordial ovarian cells, thereby suggesting their participation in non-vascular functions. Since prefollicular ovaries are insensitive to gonadotropins, the results suggest that the developing ovary becomes subjected to direct neurogenic influences before it acquires responsiveness to gonadotropins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Advis JP, Ahmed CE, Ojeda SR (1989) Direct hypothalamic control of vasoactive intestinal peptide (VIP) levels in the developing rat ovary. Brain Res Bull 22:605–610

    PubMed  Google Scholar 

  • Ahmed CE, Dees WL, Ojeda SR (1986) The immature rat ovary is innervated by vasoactive intestinal peptide-containing fibers and responds to VIP with steroid secretion. Endocrinology 118:1682–1689

    PubMed  Google Scholar 

  • Baljet B, Drukker J (1979) The extrinsic innervation of the abdominal organs in the female rat. Acta Anat 104:243–267

    PubMed  Google Scholar 

  • Ben-Jonathan N, Arbogast LA, Rhoades TA, Bahr J (1984) Norepinephrine in the rat ovary: ontogeny and de novo synthesis. Endocrinology 115:1426–1431

    PubMed  Google Scholar 

  • Ben-Or S (1963) Morphological and functional development of the ovary of the mouse. I. Morphology and histochemistry of the developing ovary in normal conditions and after FSH treatment. J Embryol Exp Morph 11:1–11

    PubMed  Google Scholar 

  • Burden HW (1978) Ovarian innervation. In: Jones RE (ed) The vertebrate ovary: comparative biology and evolution. Plenum Press, New York, pp 615–638

    Google Scholar 

  • Burden HW (1985) The adrenergic innervation of mammalian ovaries. In: Ben-Jonathan N, Bahr JM, Weiner RI (eds) Catecholamines as hormone regulators. Raven Press, New York, pp 261–278

    Google Scholar 

  • Burghardt RC, Anderson E (1981) Hormonal modulation of gap junctions in rat ovarian follicles. Cell Tissue Res 214:181–193

    PubMed  Google Scholar 

  • Dahl E (1970) Studies of the fine structure of ovarian interstitial tissue. 3. The innervation of the thecal gland of the domestic fowl. Z Zellforsch 109: 212–226

    PubMed  Google Scholar 

  • Davoren BJ, Hsueh AJW (1984) Vasoactive intestinal peptide: a novel stimulator of steroidogenesis by cultured rat granulosa cells. Biol Reprod 33:37–52

    Google Scholar 

  • Dees WL, Ahmed CE, Ojeda SR (1986) Substance P (SP) and vasoactive intestinal peptide (VIP)-containing nerve fibers reach the ovary by independent routes. Endocrinology 119: 638–641

    PubMed  Google Scholar 

  • Dissen GA, Nilaver G, Hill DF, Ojeda SR (1990) Expression of nerve growth factor receptor (NGFrec) and tyrosine hydroxylase (TH) mRNAs in the immature rat ovary (abstract). Soc Neurosci 16:296

    Google Scholar 

  • Dissen GA, Hill DF, Costa ME, Ma YJ, Ojeda SR (1991) Nerve growth factor receptors in the prepubertal rat ovary. Mol Endocrinol 5:1642–1650

    PubMed  Google Scholar 

  • Dissen GA, Malamed S, Gibney JA, Hirshfield AN, Ojeda SR (1992) Neurotrophins are required for follicular formation in the mammalian ovary. Soc Neurosci Abstr 18 (in press)

  • Ernfors P, Wetmor C, Olson L, Persson H (1990) Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron 5:511–526

    PubMed  Google Scholar 

  • Fink G, Schofield GC (1971) Experimental studies on the innervation of the ovary in cats. J Anat 109:115–126

    PubMed  Google Scholar 

  • Funkenstein B, Nimrod A, Lindner HR (1980) The development of steroidogenic capability and responsiveness to gonadotropins in cultured neonatal rat ovaries. Endocrinology 106:98–106

    PubMed  Google Scholar 

  • George FW, Ojeda SR (1987) Vasoactive intestinal peptide induces aromatase activity before development of primary follicles and responsiveness to FSH. Proc Natl Acad Sci USA 84:5803–5807

    PubMed  Google Scholar 

  • Gozes I, Tsafriri A (1986) Detection of vasoactive intestinal peptide-encoding messenger ribonucleic acid in the rat ovaries. Endocrinology 119:2606–2610

    PubMed  Google Scholar 

  • Hallbook F, Ibanez CF, Persson H (1991) Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron 6:845–858

    PubMed  Google Scholar 

  • Hertz R (1963) Pituitary independence of the prepubertal development of the ovary of the rat and the rabbit and its pertinence to hypo-ovarianism in women. In: Grady HG, Smith DE (eds) The ovary. Williams & Wilkins, Baltimore, pp 120–127

    Google Scholar 

  • Hirshfield AN (1991) Development of follicles in the mammalian ovary. Int Rev Cytol 123:43–101

    Google Scholar 

  • Humason GL (1972) Animal Tissue Techniques. Freeman, San Francisco, p 15

    Google Scholar 

  • Kannisto P, Ekblad E, Helm G, Owman C, Sjoberg NO, Stjernquist M, Sundler F, Walles B (1986) Existence and co-existence of peptides in nerves of the mammalian ovary and oviduct demonstrated by immunocytochemistry. Histochemistry 86:25–34

    PubMed  Google Scholar 

  • Karnovsky MJ (1965) A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol 27:137

    Google Scholar 

  • Klein CM, Burden HW (1988) Substance P- and vasoactive intestinal polypeptide (VIP)-immunoreactive nerve fibers in relation to ovarian post-ganglionic perikarya in para- and pre-vertebral ganglia: evidence from combined retrograde tracing and immunocytochemistry. Cell Tissue Res 252:403–410

    Google Scholar 

  • Lamprecht SA, Zor U, Tsafriri A, Lindner HR (1973) Action of prostaglandin E2 and of luteinizing hormone on ovarian adenylate cyclase, protein kinase and ornithine decarboxylase activity during postnatal development and maturity in the rat. J Endocrinol 57:217–233

    PubMed  Google Scholar 

  • Lara HE, McDonald JK, Ojeda SR (1990) Involvement of nerve growth factor in female sexual development. Endocrinology 126:364–375

    PubMed  Google Scholar 

  • Lawrence IE Jr, Burden HW (1980) The origin of the extrinsic adrenergic innervation of the ovary. Anat Rec 196:51–59

    PubMed  Google Scholar 

  • Malamed S, Gibney JA, Yamasaki DS, Carsia RV (1984) Ultrastructural evidence for adrenocortical-neuronal junctions (abstract). Anat Record 208:113A

    Google Scholar 

  • Malamed S, Gibney JA, Ojeda SR (1990) Ovarian innervation develops before initiation of folliculogenesis. Anat Rec 226:64A-65A

    Google Scholar 

  • Mohsin S, Pennefather JN (1979) The sympathetic innervation of the mammalian ovary. A review of pharmacological and histological studies. Clin Exp Pharmacol Physiol 6:335–354

    PubMed  Google Scholar 

  • Nilsson (1983) Autonomic nerve function in the vertebrates. Springer, Berlin, pp 43–44

    Google Scholar 

  • Ojeda SR, Lara H (1989) The role of the sympathetic nervous system in the regulation of ovarian function. In: Pirke KM, Wuttke W, Schweiger U (eds) The menstrual cycle and its disorders. Springer, Berlin, pp 26–32

    Google Scholar 

  • Ojeda SR, Lara H, Ahmed CE (1989) The potential relevance of vasoactive intestinal peptide to ovarian physiology. In: Adashi E (ed) Putative intraovarian regulators. Seminars in reproductive endocrinology, vol 7. Thieme, New York, pp 52–60

    Google Scholar 

  • Papka RE, Cotton JP, Traurig HA (1985) Comparative distribution of neuropeptide tyrosine-, vasoactive intestinal peptide-, substance P-immunoreactive, acetylcholinesterase-positive and noradrenergic nerves in the reproductive tract of the female rat. Cell Tissue Res 242:475–490

    PubMed  Google Scholar 

  • Peluso JJ, Steger RW, Hafez ESE (1976) Development of gonadotropin-binding sites in the immature rat ovary. J Reprod Fertil 47:55–58

    PubMed  Google Scholar 

  • Peters H, Byskov AG, Faher M (1973) Intraovarian regulation of follicle growth in the immature mouse. In: Peters H (ed) The development and maturation of the ovary and its functions. Excerpta Medica, Amsterdam, pp 20–23

    Google Scholar 

  • Peters A, Palay SL, Webster HdeF (1991) The Fine Structure of the Nervous System, 3 edn. Oxford University Press, New York, pp 8, 169–186

    Google Scholar 

  • Picon R, Pelloux MC, Benhaim A, Gloaguen F (1985) Conversion of androgen to estrogen by the rat fetal and neonatal female gonad: effects of dcAMP and FSH. J Steroid Biochem 23:995–1000

    PubMed  Google Scholar 

  • Rajah R, Hirshfield AN (1991) The changing architecture of the rat ovary during the immediate postpartum period: a three dimensional (3D) reconstruction. Biol Reprod 44 [Suppl 1]:152

    Google Scholar 

  • Sariola H, Saarma M, Sainio K, Arumae U, Palgi J, Vaahtokari A, Thesleff I, Karavanov A (1991) Dependence of kidney morphogenesis on the expression of nerve growth factor receptor. Science 254:571–573

    PubMed  Google Scholar 

  • Schwartz NB (1974) The role of FSH and LH and of their antibodies on follicle growth and on ovulation. Biol Reprod 10:236–272

    PubMed  Google Scholar 

  • Siebers JW, Schmidkke J, Engel W (1977) hCG-insensitivity of the postnatal ovary is due to the lack of a specific receptor. Experientia 33:689

    PubMed  Google Scholar 

  • Smith White S, Ojeda SR (1981) Changes in ovarian luteinizing hormone (LH) and follicle stimulating hormone (FSH) receptor content and in gonadotropin-induced ornithine decarboxylase activity during prepubertal and pubertal development of the rat. Endocrinology 109:152–161

    PubMed  Google Scholar 

  • Smolen AJ (1988) Morphology of synapses in the autonomic nervous system. J El Micr Tech 10:187–204

    Google Scholar 

  • Sokka T, Huhtaniemi I (1990) Ontogeny of gonadotropin receptors and gonadotropin-stimulated cyclic AMP production in the neonatal ovary. J Endocrinol 127:297–330

    PubMed  Google Scholar 

  • Weiss L (1988) Cell and tissue, 6th edn. Urban and Schwarzenberg, Baltimore, pp 300–302

    Google Scholar 

  • Zor U, Kliachko S (1985) The β-adrenergic system in rat ovarian granulosa cells: hormonal and prostaglandin dependence in vivo and spontaneous development in vitro. In: Ben-Jonathan N, Bahr JM, Weiner RI (eds) Catecholamines as hormone regulators. Raven Press, New York, pp 311–328

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 08854, Piscataway, New Jersey, USA

    Sasha Malamed & Jean A. Gibney

  2. Division of Neuroscience, Oregon Regional Primate Research Center, 505 N.W. 185th Avenue Beaverton, 97006, OR, USA

    Sergio R. Ojeda

Authors
  1. Sasha Malamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean A. Gibney
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sergio R. Ojeda
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Malamed, S., Gibney, J.A. & Ojeda, S.R. Ovarian innervation develops before initiation of folliculogenesis in the rat. Cell Tissue Res. 270, 87–93 (1992). https://doi.org/10.1007/BF00381883

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00381883

Key words

Search

Navigation