🚀 go-pugleaf

Leonid Gavrilov <lagavril@midway.uchicago.edu> wrote in message
news:9259eb2.0301151708.1376436e@posting.google.com...
> Greetings,
>
> I would appreciate your feedback on the issue of high cell losses in
> early development (this may be important for understanding aging).
>
> Specifically, I wonder whether the following statement is correct:
>
>  "The female human fetus at age 4-5 months possesses 6-7 million eggs
> (oocytes). By birth, this number drops to 1-2 million and declines
> even further.  At the start of puberty in normal girls, there are only
> 0.3-0.5 million eggs -- just only 4-8% of initial numbers."

I have heard this before in several places so I would guess it's true.

> Are there any other similar examples of early massive cell loss?

> Or is this story specific to oocytes only?

Early CNS neuronal losses are massive also, although it is believed to be
part of the early learning process rather than anything to do with aging.

Cheers,
Michael C Price
----------------------------------------
http://mcp.longevity-report.com
http://www.hedweb.com/manworld.htm

"michaelprice" <michaelprice@ntlworld.com> wrote in message news:<AZnV9.56$Ks.40695@newsfep1-win.server.ntli.net>...
> Leonid Gavrilov <lagavril@midway.uchicago.edu> wrote in message
> news:9259eb2.0301151708.1376436e@posting.google.com...
> > Greetings,
> >
> > I would appreciate your feedback on the issue of high cell losses in
> > early development (this may be important for understanding aging).
> >
> > Specifically, I wonder whether the following statement is correct:
> >
> >  "The female human fetus at age 4-5 months possesses 6-7 million eggs
> > (oocytes). By birth, this number drops to 1-2 million and declines
> > even further.  At the start of puberty in normal girls, there are only
> > 0.3-0.5 million eggs -- just only 4-8% of initial numbers."
> 
> I have heard this before in several places so I would guess it's true.


*** Please, could you provide any references to these important
findings ?


> 
> > Are there any other similar examples of early massive cell loss?
>  
> > Or is this story specific to oocytes only?
> 
> Early CNS neuronal losses are massive also, although it is believed to be
> part of the early learning process rather than anything to do with aging.
> 


*** Again, could you please provide any references to these important
findings on massive CNS neuronal losses?
 This may be very important for understanding aging and longevity.

Thank you!

Best wishes,


-- Leonid Gavrilov 
Author of the book "The Biology of Life Span"
 http://www.src.uchicago.edu/~gavr1/index.html#Book

Hi Leonid
  It's my understanding that a regulated form of apoptosis is a basic
feature of prenatal development throughout the Animal Kingdom as sort
of a morphological sculpting of the individual. From what I've been
reading if the
process becomes aberrant for any reason it leads to certain types of
impairment
postnatally.  Here's the results of a brief PubMed search.

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12124904&dopt=Abstract

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8944315&dopt=Abstract

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12426774&dopt=Abstract

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11889186&dopt=Abstract

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9694591&dopt=Abstract

www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9448042&dopt=Abstract


Regards
   Tim

Tim <timothytn@my-deja.com> wrote

> Hi Leonid
>   It's my understanding that a regulated form of apoptosis is a basic
> feature of prenatal development throughout the Animal Kingdom as sort
> of a morphological sculpting of the individual. From what I've been
> reading if the
> process becomes aberrant for any reason it leads to certain types of
> impairment
> postnatally.

Yes, that's what I heard as well.  One other instance I can think of
is the apoptosis of the fetal inter-digital webbing, prior to birth.

Cheers,
Michael C Price
----------------------------------------
http://mcp.longevity-report.com
http://www.hedweb.com/manworld.htm

Leonid Gavrilov <lagavril@midway.uchicago.edu> wrote

>>> Specifically, I wonder whether the following statement is correct:
>>>
>>>  "The female human fetus at age 4-5 months possesses 6-7 million eggs
>>> (oocytes). By birth, this number drops to 1-2 million and declines
>>> even further.  At the start of puberty in normal girls, there are only
>>> 0.3-0.5 million eggs -- just only 4-8% of initial numbers."
>>
>> I have heard this before in several places so I would guess it's true.
>
>
> *** Please, could you provide any references to these important
> findings ?

This is probably duplicating some of Tim's finds, but, what the heck, it's
easier just to blast them out than check.

J Clin Endocrinol Metab 2001 Jul;86(7):3421-9 Related Articles, Links

Survival of human ovarian follicles from fetal to adult life: apoptosis,
apoptosis-related proteins, and transcription factor GATA-4.

Vaskivuo TE, Anttonen M, Herva R, Billig H, Dorland M, te Velde ER, Stenback
F, Heikinheimo M, Tapanainen JS.

Department of Obstetrics and Gynecology, University of Oulu, FIN-90220 Oulu,
Finland.

The majority of oocytes present in fetal ovaries are depleted before birth,
and only about 400 will ovulate during the normal fertile life span. Studies
on animals have shown that apoptosis is the mechanism behind oocyte
depletion and follicular atresia. In the present study, we investigated the
extent and localization of apoptosis in human fetal (aged 13-40 weeks) and
adult ovaries. Furthermore, the expression of apoptosis-regulating proteins,
bcl-2 and bax, and the relationship of transcription factor GATA-4 were
studied. Apoptosis was found in ovarian follicles throughout fetal and adult
life. During fetal development, apoptosis was localized mainly to primary
oocytes and was highest between weeks 14-28, decreasing thereafter toward
term. Expression of bcl-2 was observed only in the youngest fetal ovaries
(weeks 13-14), and bax was present in the ovaries throughout the entire
fetal period. In adult ovaries, apoptosis was detected in granulosa cells of
secondary and antral follicles, and Bcl-2 and bax were expressed from
primary follicles onwards. During fetal ovarian development, GATA-4
messenger RNA and protein were localized to the granulosa cells, with
expression being highest in the youngest ovaries and decreasing somewhat
toward term. The expression pattern of GATA-4 suggests that it may be
involved in the mechanisms protecting granulosa cells from apoptosis from
fetal to adult life. The results indicate that depletion of ovarian
follicles in the human fetus occurs through intrinsic mechanisms of
apoptosis in oocytes, and later in adult life the survival of growing
follicles may be primarily determined by granulosa cell apoptosis.

PMID: 11443219

Anticancer Res 1998 Sep-Oct;18(5A):3457-61 Related Articles, Links

Apoptosis in different stages of human oogenesis.

De Pol A, Marzona L, Vaccina F, Negro R, Sena P, Forabosco A.

Dipartimento di Scienze Morfologiche e Medico Legali, Universita di Modena,
Italia.

Apoptosis is an active form of cell death characterized by a series of
morphological changes that become particularly evident at the
ultrastructural level. The majority of ovarian germ cells undergo
degeneration during prenatal and reproductive life and only in recent
studies has it been demonstred that this drop is due to an apoptotic
process. We evaluated this process during human oogenesis in prenatal life
and we studied the ultrastructural changes that occur in apoptosis in
various phases of the meiotic process. From our observations it is clear
that apoptosis involves two main phases of the meiotic process: an earlier
one concerning the oogonia and oocytes in the preleptotene stage, and a
later one that mainly concerns the oocytes in the pachytene stage.

PMID: 9858924
>>
>> > Are there any other similar examples of early massive cell loss?
>>
>> > Or is this story specific to oocytes only?
>>
>> Early CNS neuronal losses are massive also, although it is believed
>> to be part of the early learning process rather than anything to do
>> with aging.
>>
>
>
> *** Again, could you please provide any references to these important
> findings on massive CNS neuronal losses?
>  This may be very important for understanding aging and longevity.

I haven't checked but I believe the neuronal loss continues after birth.
>
Trends Neurosci 2000 Oct;23(10):454-8

Cell death in early neural development: beyond the neurotrophic theory.

de la Rosa EJ, de Pablo F.

Dept of Cell and Developmental Biology, Centro de Investigaciones
Biologicas, CSIC, Velazquez 144, E-28006, Madrid, Spain.

The important effect of cell death on projecting neurons during development
is well established. However, this mainstream research might have diverted
recognition of the cell death that occurs at earlier stages of neural
development, affecting proliferating neural precursor cells and young
neuroblasts. In this article, we briefly present observations supporting the
occurrence of programmed cell death during early neural development in a
regulated fashion that to some extent parallels the death of projecting
neurons lacking neurotrophic support. These findings raise new questions, in
particular the magnitude and the role of this early neural cell death.

Publication Types:
Review
Review, Tutorial

PMID: 11006461

: Eur J Neurosci 2000 Aug;12(8):2721-34 Related Articles, Links


Programmed cell death in the developing human telencephalon.

Rakic S, Zecevic N.

Department of Neuroscience, University of Connecticut Health Center,
Farmington, Connecticut 06030-3401, USA.

Programmed cell death (PCD) in the form of apoptosis is recognized as one of
the central events in the development of the central nervous system. To
study the time of onset, extent and distribution of PCD in the human
telencephalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.)
were examined using the TUNEL (TdT-mediated dUTP-biotin nick-end labelling)
in situ method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the
ventricular zone of the neural tube. With the formation of the cortical
plate at 7-8 g.w. , TUNEL(+) nuclei were seen in all developmental layers of
the cortical anlage, as well as in the subcortical regions such as the
ganglionic eminence and the internal capsule. The proliferative zones (the
ventricular zone, the subventricular zone and the ganglionic eminence)
contained the majority of all apoptotic nuclei observed in each specimen.
However, the apoptotic index was highest in the subplate zone and in layer
I. Double-labelling experiments suggested that neuronal precursors were the
main population of cells undergoing PCD in the first trimester of gestation,
whereas glial cells probably start dying around midgestation. The onset of
labelling of microglial cells and apoptotic nuclei were synchronous,
indicating the involvement of microglia in PCD. In conclusion, two distinct
types of PCD were observed during human telencephalic development: embryonic
apoptosis, which was synchronous with proliferation and migration of
neuronal cells and probably not related to establishment of neuronal
circuitry, and fetal apoptosis, which coincided with differentiation and
synaptogenesis, and therefore may be related to the development of
axonal-target connectivity.

PMID: 10971615
: Dev Neuropsychol 2001;19(2):211-36 Related Articles, Links


Prenatal neurobiological development: molecular mechanisms and anatomical
change.

Monk CS, Webb SJ, Nelson CA.

Institute of Child Development, University of Minnesota, USA.
christopher.monk@nih.gov

During prenatal development, the central nervous system is transformed from
a thin layer of unspecified tissue into a complex system that can process
information and organize actions. There are 8 general mechanisms that permit
this transformation: neural induction, neurulation, proliferation,
migration, axonal outgrowth, synaptogenesis, differentiation, and apoptosis.
These processes as well as the anatomical changes they cause are described.
Future research with humans, such as in utero MRI as well as behavioral and
electrophysiological testing of infants following specific prenatal
perturbations, is suggested to link the findings from molecular approaches
to developmental neuropsychology.

Publication Types:
Review
Review, Tutorial

PMID: 11530976
Mol Neurobiol 2000 Aug-Dec;22(1-3):41-54

Neural activity and survival in the developing nervous system.

Mennerick S, Zorumski CF.

Department of Psychiatry, Washington University School of Medicine, St.
Louis, MO 63110, USA.

Recent evidence suggests that blockade of normal excitation in the immature
nervous system may have profound effects on neuronal survival during the
period of natural cell death. Cell loss following depression of electrical
activity in the central nervous system (CNS) may explain the
neuropsychiatric deficits in humans exposed to alcohol or other CNS
depressants during development. Thus, understanding the role of electrical
activity in the survival of young neurons is an important goal of modern
basic and clinical neuroscience. Here we review the evidence from in vivo
and in vitro model systems that electrical activity participates in
promoting neuronal survival. We discuss the potential role of moderate
elevations of intracellular calcium in promoting survival, and we address
the possible ways in which activity and conventional trophic factors may
interact.

Publication Types:
Review
Review, Academic

PMID: 11414280
Exp Neurol 1999 Mar;156(1):1-15 Related Articles, Links


Apoptosis in neuronal development and transplantation: role of caspases and
trophic factors.

Boonman Z, Isacson O.

Neuroregeneration Laboratories, Harvard Medical School, Program in
Neuroscience, McLean Hospital, MRC 119, 115 Mill Street, Belmont,
Massachusetts 02478, USA.

Fetal ventral mesencephalic (VM) transplants have been studied in the
context of dopaminergic (DA) replacement therapy for Parkinson's disease
(PD). DA neurons from VM transplants will grow axons and form functional
synapses in the adult host central nervous system (CNS). Recently, studies
have demonstrated that most of the transplanted DA neurons die in grafts
within the first week after implantation. An important feature of neural
development, also in transplanted developing fetal neural tissue, is cell
death. However, while about 50% of cells born in the CNS will die naturally,
up to 99% of fetal cells die after neural transplantation. It has been shown
that VM grafts contain many apoptotic cells even at 14 days after
transplantation. The interleukin-1beta converting enzyme (ICE) cysteine
protease and 11 other ICE-like-related proteases have been identified, now
named caspases. Activation of caspases is one of the final steps before a
neuron is committed to die by apoptosis. Here we review this cell death
process in detail: Since the growth of fetal neural grafts placed in the
adult brain in many ways mimics normal development, it is likely that the
caspases also play a functional role in transplants. Pharmacological
inhibitors of caspases and genetically modified mice are now available for
the study of neuronal death in fetal neuronal transplants. Understanding
cell death mechanisms involved in acute cellular injury, necrosis, and
programmed cell death (PCD) is useful in improving future neuronal
transplantation methodology, as well as in neuroprotection, for patients
with neurodegenerative diseases. Copyright 1999 Academic Press.

Publication Types:
Review
Review, Academic

PMID: 10192773
> Thank you!

>
> Best wishes,
>
You're welcome.
Cheers,
Michael C Price
----------------------------------------
http://mcp.longevity-report.com
http://www.hedweb.com/manworld.htm

And another:

Nat Rev Mol Cell Biol 2002 Oct;3(10):779-87 
  
How death shapes life during development.

Baehrecke EH.

Center for Biosystems Research, University of Maryland Biotechnology
Institute, College Park, Maryland 20742, USA. baehreck@umbi.umd.edu

The formation of an adult animal from a fertilized embryo involves the
production and death of cells. Surprisingly, many cells are produced
during development with an ultimate fate of death, and defects in
programmed cell death can result in developmental abnormalities.
Recent studies indicate that cells can die by many different
mechanisms, and these differences have implications for proper animal
development and disorders such as cancer and autoimmunity.

Publication Types: 
Review 
Review, Academic 

PMID: 12360194