collagen tertiary structure
ovary its development and fucntions IN HEALTH AND DISEASE -series I
OVARIAN DEVELOPMENT series i
by Ghulam Mohyuddin Wani BVSC&AH,MVSC[VOG]DVM,PhD,
Gazanfer Wani MBBS AND Paras Wani BUMS,
INTRODUCTION.
We understand the difficulity of phsicians and patiens in deveoping a harmony and understanding due to different knowledge perceptions.Here we try to reveiw all the physiological ,endocrinological and phathological aspects of ovary in a simple language so that both the groups can use and benefit from it.This is our first attempt to club Tibia (UNANI or Greek),Allopathy {Human and animal}AT ONE PLACE TO ACQUINT OUR READERS about the researches done in the recent times.As this shall be a more outreach type of presentations,we shall request the readeras to go through our other papers too to understamd fully the concepts gathered or hinted here.It is not a repatition of our earlier papers on the topic but a revision and many new investigations carried round the globe have benn added,We hope to have a feed back from all of you and bring a book for our readers in future.As such we wish you to act as our unknown peer and reviewer,
Ovaries are the generative organs of mammals for the production of female gamates.The female eggs consist of the protective coverings and a few layers of cells wchich initially surround the female egg called oocyte.
Ovaries perform a dual function.
EXOCRINE
Under exocrine functions they release oocyte .
ENDOCRINE
Under endocrine function they release ovarian hormones.
OOGENESIS
It is the name given to the process of egg formation within the ovaries of the mammals.The process is initiated during mammalian foetal life.Its beginning and end differs with species.(WANI,1984,1996.2009]. The oogenesis begins around 7th
Month of embryonic life of a female.Millions of primodial follicles appear in the cotex of the developing foetal ovary. This number of primodial follicles is species specific and progressively diminishes upto menopause in women and with age in other mammals.A fetal lamb or kid[GOAT]has millions but only 85 thousand such follicles are estimated to be present at pubertal oestrus,indicating a lossfrom fatal to birth and then birth to puberty.A female cow calf has around a 100 thousand such follicle at first oestrus ie puberty..
The women has 200 thousand at puberty from a birth pool of 500 thousand numbers as they are not seasonal but have poly cyclic recieptivity,which other wise a misnomer or exception in other species.We did confirm the occurance of gestational heats in small ruminants tooSinha et al 1980 and wani et al 1980.The number of these follicles progressively decreases with age, more rapidly with approaching puberty or adolescence.
PUBERTY
The first menarchy is indicative of the puberty in women.Simmilarly the first oestrus is the beginning of puberty in other mammals.This may be one of the causes of low fertility in women who decide to marry at an older age.
PRIMODIAL FOLLICLE
The primodial follicle consist of an oocyte surrounded by a flat stromal cells or somatic cells called granulosa cells. This primitive oocyte, is called oocyte I. (Guerin, 2009). The granulosa cells are covered by a basal membrane known as membrane of Slavjan Ski. The diameter of oocyte I is around 30 µm.
The primodial follicle changes to primary follicle.The primodial follicle consists of a flat layer of germinal cells.When these flat cells change to a cuboidal shape the follicle is named as secondry follicle.
SECONDARY FOLLICLE.
It still contains OOCYTE I inside.It has a double layer of germinal cells cuboidal in shapeThe size of OOCYTE I within it measure around 40 µm.
GRANULOSA CELL GROWTH.
The number of granulosa cell increase and are around 5000 in number. The oocyte grows too and its diameter measure over 60 µ. The follicle is still categorized as secondary follicle and its size may increase with oocyte reaching a diameter of 180 µm inside it. Thus primary to secondary follicle transit involves 6 fold growth in the diameter of the oocyte.
During last stages of secondary follicles isolated islands or space differentiate within multiplying gransulosa cell layers which differentiate epitheloid cells from stroma fibroblasts.
OVARIAN HAEMODYNAMICS
The blood capillary ramification or what is named ovarian haemodynamic development and described as angiogenic changes in ovarian development of sheep (Wani, 2009, Khatun & Wani, 2007, Khatoon et al. 2006, Goswani et al. 2008).
PRE-ANTRAL FOLLICLE
The epitheloid cells surrounded by encapsulating angiogenic masses give rise to what is known as theca interna or inner layer of the follicle. This secondary follicle in which theca interna is visible is called Pre-antral follicle. The formation of cavity is pecular recognition of the pre-antral follicle.
THE TERTIARY OR ANTRAL FOLLICLE
The follicle grows and granulosa cells now differentiate into theca externa and theca interna with a central antrum . The follicle is named as tertiary follicle. The rapid growth and differentiation of follicular (granulosa) cells continues and cells become innumerable around 50 million. The tertiary follicle grows in diameter and reaches a size of about 20 mm or 2 cms.
PRE-OVULATORY FOLLICLE
The size of the preovulatory follicle is around 20 mm or 2 cms. Any tertiary follicle assuming or attaining this growth is denoted as pre-ovulatory follicle. The differentiation of granulosa cell as theca interna now culminates into another type of cells called theca externa. The oocyte within a particular mass of granulosa cell now invaginates into follicular cavity.
CUMULUS OOPHORUS
The electron microscopy of these theca cells denoted as cumulus oophurus(theca interna derived cell) has shown that it consists of;
clusters of epitheloid cells
ANGIOGANIC CHANGES
The theca externa layer consists of collagen fibers penetrated by numerous blood capillaries. These angiogenic ovarian changes are vivid and transparent. The usual fibroblasts of early follicles change to myofibroblasts at this stage
PRE-OVULATORY FOLLICLE
Preovulatory follicle in women contains oocyte still at the diakinesis stage .Withthe cytoplasmic growth of the oocyte corresponding follicle also grows,. At this stage oocyte, measure 120 µm in diameter.
OOCYTE CHANGES .
Oocyte too undergoes some changes at preovulatory stage. The cytoplasm and nucleus continue to grow. Cortical granules migrate to the periphery. It is these granules which blast like radio active nuclear materials and form a firm protective cover around the “fertilized ovum” known as cortical reactions.
Zona reaction
This reaction is displayed and commonly known as Zona reaction.The other inner membrame of the oocyte is called vitteline membrane and its block is called vitellane block.
- They prevent polyspermy at fertilization. These cortical granules are radio-opaque substances which expand like a nuclear mushromm and shadows the wall of the oocyte at fertilization. These cortical granules from cytoplasm of the preovulaty follicle.shift and merge with plasma membranes.
OOCYTE DEVELOPMENT & ACTIVATION
While these changes are occurring the nuclear material of oocyte I at blocked level too resumes activity but soon its activity is arrested and Block II comes into force. This block effectuates at 2nd metaphase division (Metaphase II). Thus there is now established evidences that oocyte of its own resumes nuclear activity which progresses from Propase I to Metaphase II well within the ovarian life.
PARTHENOGENESIS
Is it possible to explore the circumstances, modulators and precursors of this change.? More investigation on this topic are needed. This would possibly explain the growth. and maturation of follicle of its own as it happens in parthenogenesis or even after Menopause it would be possible to incite such changes.
BIRTH OF CHIRST-THE HOLLY SPIRIT .
Once the mechanism triggering this change from Propase to Metaphase is signaled out, we may explain the process of the birth of Messiah “Haroon” or “Issac” from unmarried and aged parents as referred to in Holly Quran for the first time in literature in 579 AD.
This self initiating change within the oocyte to overcome its nuclear development block can be hypothesis for a broad new concept on foliculogenesis, which would fulfill the wishes of infertile and aged couple and give them a new hope for their loved procreation even after death.
LIFE AFTER DEATH IS POSSIBLE
The post death revival of life in slaughtered sheep has been achieved. (Wani, 1995, Wani, 2001, 2004, 2006, 2008, 2009, 1996 Figures 1-3)
During ovulation, propelled by the activity of myofibroblasts in the theca cells, the oocyte I is virtually changed to oocyte II with the above mentioned changes. The released “ovum” in women is thus oocyte II surrounded by cumulus cells. The stage at which oocyte are released in mammals have been reported (Wani 1996).
The figures of this chapter show our own results of oocyte maturation and fertilization after death (WANI 1995,WANI ,1996,WANI ET AL 1997,2000).
The oocyte were recovered, grown and matured invitro within 12-20 hrs of slaughtering the animals. Fertilizing the recovered and matured in-vitro oocytes with semen obtained from the slaughtered Ram epidylimus . This innovative research opens a new erea of post death revival of life and also explains the truths recorded for the first time in the book of GOD “THE Holy Quran “
Primodial Germ Cell Pool
Premodial follicle remain in dormancy since its formation during foetal life upto puberty i.e. around 15 years in women,few months 12-15 months in sheep and goats,2-3 years in cattle and buffalos.The puberty age and the status of follicles has been reported and reviewed by wani1984.
Out of the primodial follicular pool or commonly referred to germ cell pool by many authors including we in our books and thesis (Wani, 1984, 1984 b, 1996, 2006, 2008, 2009). Only a few grow ,still fewer mature and futher only one ovulates at each cycle.
At puberty their number in humans is known to have decreased to 2 million from original fetal pool of 5 million at birth. . I must emphasize all these number are postulations or calculations on statistical assumption. Only “God’ known the true number. However, reviewing the available knowledge on this date of 18th of December ,2009, when I am writing this chapter all literary and investigative figures indicate 5 million at birth and around 2 million at puberty. The significant loss of the germ cell pool occurs ,first between fetal ovarin development and irth,the second cut on the follicles occurs between birth and puberty and progressive cuts and reduction ensues at each oestrus or menusturial cycle with its decrease or near ceseatio during old age,Women have been seen to have decreased rates at or near menopause.. We today precisely
do not know ,whether this loss between birth and puberty is similar in fertile and infertile women or there is complete ceseation of follicle development after menopause.
There are possibly two explanation which could be unveiled in future. In simple terms the answer to my self proposed question could be yes. Yes means fertile women have less loss of primodial follicles in their physiological change from childhood to adulthood. This would means more number of follicle available for ovulation or perhaps a ratio exists within developmental process to have a fixed number of pool to recruit and classify future ovulating follicles. The negative answer will take us to wander world of Endocrindogy where morphological evidences alone could not prove the point, but yes one would analyse the degree of success in assisted fertility cases. How and when this would be known is perhaps beyond my vision. Atleast in my life I do not foresce a revolution of this kind as very few follicular biologists are active on earth.
Perhaps prioritizing of foetal-maternal interactions by WHO / UNDEP/ USAD/ CAR. Such other world research organisation may help. Alternatively, a research donation by an infertile couple (who underand the desperation of millions suffering from infertility) may help us to unveil the hidden potential .
As on today the mechanism of folliculogenesis is so inefficient that out of a pool of 7 million prospective eggs (Primodial follicles) hardly 4000 follicles reach preovulatory stage. A new knowledge poor is available on folliculogenesis. Many confusing terms have been reported we may try to present here simple definition of these terms used by us and many authors.
Initial follicular Recruitment
This is the process when primodial follicle development arrested at birth regain their capacity to grow. Local growth promoting factors have been found to be responsible for this wakeup call. Research review shows inhibitory process is responsible for the primodial follicular sleep. This deep sleep can be or is known to broken by stimulatory factors. These inhibitory and stimulatory factors have been researched.
The primary follicles containing oocytes.
Here at this stage the oocyte genome is activated. This activation has been reported as Transcription of gene. This is what needs further elucidation. What is that nature of this transcribed gene. During this phase of the foliculogenesis a significant development has been searched out. This is what is called paracrine signaling pathway. These paracrine signaling pathways reported are responsible for communicating signals from follicle or granulosa cells to the inside trapped oocyte. The growth of the oocyte is concomitant and proportionately comparable. This signaling mechanism have increased embryo culture success rate by use of cumulus cells in the co-culture{WANI,2001,1996}
CO -CULTURE PROCEDURES
The co-culture with cumulus cells have become a routine procedure in these days.Two recepyivity theories have been postulated and are now though help co-cultures to gain a higher success rate. Two recieptivity waves formulate the destiny of the primary follicle as follows:
Endocrine Recieptivity : is attainted by the follicular wall of few layer thick in this primary follicle. It is found that FSH receptor develop in these follicular cell which make primary follicles responsive to FSH. Thus, we could say that two, recieptivity waves formulate the destiny of the primary police.
First is Exocrine(EXR):
Recieptivity in which a communication mechanism with “oocyte” is established. A communication system between primary follicle cells and oocyte inside.
Second is Endocrine(ENR):
Recieptivity which establishes receptors within primary follicular cells for FSH. (Follicle-Stimulating Hormone). Now it is established that all follicle do not respond to FSH; it is only primary follicle who respond to it. We may not wonder if Endocrinologits in future rename FSH as PFSH.
Primary Follicle Stimulating Hormone(PFSH):
During this phase of primary follicle transition, oocyte covering accumulates cortical granules on a glycoprotein polymer. This capsule encircling oocyte comes to be recognized as future Zona-pellucida. This is virtually first separation (physically or morphological) of oocyte from the follicular wall. Is it that this morphological change prelude the future changes and pathways.
Paracrine Signalling Pathway (PSP):
- Does the above described morphological change initiates the PSP. Future research may show, whether paracrine signaling pathways initiate endocrine response or vise-versa. Similarly the nature of endocrine response towards cortical granule movement and subsequent formation of Zona-pellucida is the singular function of exocrine or endocrine signals or a combination of both. Thus future research in this era should involve a biologist (embryologist) biochemist (biotechnologist) and endocrinologist if all hidden secrets of this tiny mass of 01. mm diameter is to be revieled.
The primary follicles are still single layered cells, the nature of these calls have changed form flat to cubiodal form. Here it is important to note that the old concept of endocrine response to FSH by multilayer follicle is somewhat reformed. The changes for hormonal response to FSH initiate even when primary follicles are single layered but their form has to change from flat to cubiodal shaped cells. The exact mechanism of this control is to be further investigated.
MOHY HYPOTHSIS
- If some one comes out with a {follicular switch} enhancing response of the follicles to FSH, we may succeed in recovering the otherwise 3 million pool at birth and 2 million loss at puberty. A new biotechnology of follicles is in offering for future folliculogenetists.All the donor agencies the DST,ICMR,ICAR,WHO,FAO need to come with liberal support for these ideas and new research agenda.
SECONDARY FOLLICLE
The two layered granulosa cell cover around an oocyte makes a secondary follicle. A secondary follicle is a multilayered follicle.The exocrine signaling pathway is a two-way-process communicating signals from oocyte to granulosa cells and vise-versa.
Here within secondary follicle , oocyte secrets signals to initiate changes in the follicular wall.The differentiation of follicle outer coat called Lamina Propia or Basal Lamina is the result of these signals.
They further undergo cytological changes and differentiate into THECA EXTERNA and THECA INTERNA CELLS.
Both these layers or thecas are interconnected by blood capillaries. During its development a primary follicle is recognized as one with thick zona-pellucida, 9 layer granulosa cells,theca interna, theca externa and a capillary net.
About the Author
may be when we are no more some one of our genotype can realise to serve knowledge . Espacially written for the Maryam and sarah the two yet to grow and read these scripts after 20 years from now.May be these tiny creatures of my lineage shall remember a grandpapa and his motto to serve the humanity without greed ,creed and any prejudice.A dynasty ethecal code to be inscribed,
