Talk:Ovary Development

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The ovary: basic biology and clinical implications

http://www.ncbi.nlm.nih.gov/pubmed/20364094

http://www.jci.org/articles/view/41350

Aging of the human ovary and testis

Aging of the human ovary and testis. Perheentupa A, Huhtaniemi I. Mol Cell Endocrinol. 2009 Feb 5;299(1):2-13. Epub 2008 Nov 18. Review. PMID: 19059459 |


Compare these 2 different findings on new adult follicles

oocyte population is not renewed in transplanted or irradiated adult ovaries

The oocyte population is not renewed in transplanted or irradiated adult ovaries. Begum S, Papaioannou VE, Gosden RG. Hum Reprod. 2008 Oct;23(10):2326-30. Epub 2008 Jul 1. PMID: 18596027

BACKGROUND: According to conventional theory, the oocyte population is not renewed in mammalian ovaries after birth. A new hypothesis proposes that oocytes are generated continuously from haematopoietic progenitor cells. There is, however, no evidence that they can ovulate, although they may partially restore fertility by organizing 'helper follicles'. The hypothesis that follicles can form de novo in adult ovaries has been tested in a transplant model. METHODS: Ovaries from adult mice were transplanted under the kidney capsule or into the ovarian bursa of histocompatible, transgenic CAG::H2B-EGFP host animals. Some donors were sterilized before transplantation by X-irradiation to ensure 'empty niches' were available for repopulation. The phenotype of follicular oocytes at 2, 4 and 8 weeks post-transplantation was scored by epifluorescence. RESULTS: A total of 819 oocytes were examined in 30 ovarian grafts. None expressed green fluorescence, as would be predicted if they had formed de novo from germ cell progenitors in the systemic circulation of the host. Furthermore, small follicles eliminated by irradiation were not replaced in transplanted ovaries, and the few growing follicles present were apparently survivors of the original population. CONCLUSIONS: No evidence was found to support the hypothesis that progenitor cells from extra-ovarian sources can repopulate the adult ovary. The findings are consistent with the conventional view that a limited number of oocytes are formed before birth and declines with age. The study did not, however, rule out the possibility that germline stem cells may reside in the adult ovary.


new primary follicles in adult human and rat ovaries

  • Origin of germ cells and formation of new primary follicles in adult human ovaries. Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB. Reprod Biol Endocrinol. 2004 Apr 28;2:20. PMID: 15115550 | Reprod Biol Endocrinol.
" During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25-30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles."
"Follicular atresia - Atresia of primary follicles is common during the reproductive period of human females [51]. Our observations suggest that it is a rapid process, assisted by the massive influx of macrophages. The process resembles immune-system mediated corpus luteum regression [94]. Gougeon suggested that depletion of the primary follicle pool is caused mainly by atresia in younger women and by entrance into the growing pool in older women, with the change-over at 38 ± 2.4 years [54]. Since cyclic ovarian function continues in "early premenopausal" women, we speculate that ~10000 primary follicles detected during the age period 40–44 years (Fig. 15B) is a sufficient depot for continuation of ovulatory ovarian function. A 50000 difference compared to younger females fits well with the observation that 70–95% of oocytes in primary follicles show various stages of degeneration [51,52]. It appears that Gougeon was right, and it is possible to conclude that the pool of healthy primary follicles is at least 10000 during the reproductive years."
"In adult mammalian ovaries, 70–95% of oocytes are in various stages of degeneration [51,52].

51. Ingram DL: Atresia. In The Ovary (Edited by: Zuckerman S). London: Academic Press 1962, 247-273.

52. Erickson BH: Development and senescence of the postnatal bovine ovary. J Anim Sci 1966, 25:800-805. PubMed Abstract


  • Study origin of germ cells and formation of new primary follicles in adult human and rat ovaries. Bukovsky A, Gupta SK, Virant-Klun I, Upadhyaya NB, Copas P, Van Meter SE, Svetlikova M, Ayala ME, Dominguez R. Methods Mol Biol. 2008;450:233-65. PMID: 18370063
"The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females."

WNT4 ovarian cell survival

  • WNT4 is expressed in human fetal and adult ovaries and its signaling contributes to ovarian cell survival.

Jääskeläinen M, Prunskaite-Hyyryläinen R, Naillat F, Parviainen H, Anttonen M, Heikinheimo M, Liakka A, Ola R, Vainio S, Vaskivuo TE, Tapanainen JS. Mol Cell Endocrinol. 2010 Apr 12;317(1-2):106-11. Epub 2009 Dec 3. PMID: 19962424

"WNT4 plays an important role in female sexual development and ovarian function. WNT4-deficiency leads disturbed development of the internal genitalia in mouse and human, and to a dramatic reduction of mouse oocytes. However, the expression and role of WNT4 in human ovaries is yet unknown. The expression of WNT4 mRNA and protein was studied in human adult and fetal ovaries (gestational ages 12-41 weeks), and the role of WNT4 in oocyte apoptosis was investigated in WNT4-deficient mice. WNT4 mRNA and protein were present in human ovaries throughout fetal development and in different follicular stages in adult ovaries. Compared with wild-type mice, WNT4-deficient mice had a markedly enhanced rate of oocyte apoptosis, with the highest values at gestational ages of 14.5 and 16.5 days post-coitum. The current results support a view that WNT4 may have a role in oocyte selection and follicle formation and maturation in human ovaries."


Stem cell support of oogenesis

Stem cell support of oogenesis in the human. Abban G, Johnson J. Hum Reprod. 2009 Dec;24(12):2974-8. Epub 2009 Aug 17. PMID: 19687054

Stem cells in aged mammalian ovaries. Virant-Klun I, Skutella T. Aging (Albany NY). 2010 Jan 26;2(1):3-6.PMID: 20228938 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837201/?tool=pubmed

"Ovarian surface epithelium (OSE) is an important structure of the human ovary and is involved in both reproductive function and ovarian tumor formation. Primordial germ cells (PGCs) in embryonic ovaries are of extraovarian origin, but those developing during the fetal period are derived from the OSE.

primordial pool of follicles

The primordial pool of follicles and nest breakdown in mammalian ovaries. Tingen C, Kim A, Woodruff TK. Mol Hum Reprod. 2009 Dec;15(12):795-803. Epub 2009 Aug 26. Review. PMID: 19710243 | Mol Hum Reprod.

"The creation of the pool of follicles available for selection and ovulation is a multi-faceted, tightly regulated process that spans the period from embryonic development through to the first reproductive cycle of the organism. In mice, this development can occur in mere weeks, but in humans, it is sustained for years. Embryonic germ cell development involves the migration of primordial germs cells to the genital ridge, and the mitotic division of germ cell nuclei without complete cytokinesis to form a multi-nucleated syncytia, or germ cell nest. Through combined actions of germ cell apoptosis and somatic cell migration, the germ cell nuclei are packaged, with surrounding granulosa cells, into primordial follicles to form the initial follicle pool. Though often dismissed as quiescent and possibly uninteresting, this initial follicle pool is actually quite dynamic. In a very strictly controlled mechanism, a large portion of the initial primordial follicles formed is lost by atresia before cycling even begins. Remaining follicles can undergo alternate fates of continued dormancy or selection leading to follicular growth and differentiation. Together, the processes involved in the fate decisions of atresia, sustained dormancy, or activation carve out the follicle pool of puberty, the pool of available oocytes from which all future reproductive cycles of the female can choose. The formation of the initial and pubertal follicle pools can be predictably affected by exogenous treatment with hormones or molecules such as activin, demonstrating the ways the ovary controls the quality and quantity of germ cells maintained. Here, we review the biological processes involved in the formation of the initial follicle pool and the follicle pool of puberty, address the alternate models for regulating germ cell number and outline how the ovary quality-controls the germ cells produced."

PAR6, A Potential Marker for the Germ Cells Selected to Form Primordial Follicles in Mouse Ovary

PAR6, a potential marker for the germ cells selected to form primordial follicles in mouse ovary. Wen J, Zhang H, Li G, Mao G, Chen X, Wang J, Guo M, Mu X, Ouyang H, Zhang M, Xia G. PLoS One. 2009 Oct 7;4(10):e7372. PMID: 19809506

http://www.ncbi.nlm.nih.gov/pubmed/19809506

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0007372

"Partitioning-defective proteins (PAR) are detected to express mainly in the cytoplast, and play an important role in cell polarity. However, we showed here that PAR6, one kind of PAR protein, was localized in the nuclei of mouse oocytes that formed primordial follicles during the perinatal period, suggesting a new role of PAR protein. It is the first time we found that, in mouse fetal ovaries, PAR6 appeared in somatic cell cytoplasm and fell weak when somatic cells invaded germ cell cysts at 17.5 days post coitus (dpc). Meanwhile, the expression of PAR6 was observed in cysts, and became strong in the nuclei of some germ cells at 19.5 dpc and all primordial follicular oocytes at 3 day post parturition (dpp), and then obviously declined when the primordial follicles entered the folliculogenic growth phase. "

Mouse TEX14 is required for embryonic germ cell intercellular bridges but not female fertility

http://www.biolreprod.org/content/80/3/449.long


endocannabinoid system

Localisation and function of the endocannabinoid system in the human ovary. El-Talatini MR, Taylor AH, Elson JC, Brown L, Davidson AC, Konje JC. PLoS One. 2009;4(2):e4579. Epub 2009 Feb 24. PMID: 19238202

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004579