New Generation Reproductive Technologies (stem Cell-nanotechnology)

I. Advances in Embryonic and Placental Developmentenvironment and behavioral patterns need to be
1.Abstract:studied and co-related to develop a manipulative and
Early embryonic development needs detailedcurative safe system. In some species CL of
investigations if we have to reduce embryonicpregnancy is necessary till delivery, in others it is
mortality. Embryonic mortality details have beenneeded only till placenta develops. Its complete
reviewed (wani, 2005). The reproductive abnormalitiesgenesis and biostimulation and bioregulatory roles are
have been discussed and a sequential photographicobscure and needs further research.
presentation of embryonic mortality have recently10. Dominant follicle dynamics
been published (Khatoon et al 2007). The criticalThe dominant follicle dynamics may be in focus for
period when maximum embryonic losses go unnoticedovulation control. Dominant follicle or would be bride
is the period before attachment. Losses before actualat each ovulation appears around day 7 of cycle in
union of foeto-maternal tissues can be missed andwomen. It occurs much earlier on day- 1 to 0 in
calculations of embryonic mortality estimates remainruminants (cow, sheep,goats). This time point may be
unaccounted for. Some recent studies of (Wani 2006,the focus to try future selective interferences in
Khatoon et al 2006) have paved a new innovativeovulation control. Antagonist use during this phase has
model for investigation on foeto-maternalshown decreasing levels of estrogens in serum
development and its attachment. This paperthereby indirectly hinting at dominant follicle alteration,
describes the detailed embryonic development,as it is one of chief source of this hormone during
blastocyst elongation, formation of cotyledons withinthis phase (Fraser, 1987). Dominant follicle in its
elongated blastocyst, their ramifications andsojourn to freedom and release at ovulation seems
networking of vasculature and formation of foetalto attain some specific qualities. Why? It alone
placental unit. Conversely, a detailed photographicreleases itself from bondages in ovary (ovulation) and
evidence of uterine receptivity, formation of arest of its competitors are hindered through the
multicoated immunological barrier- the beginning ofprocess as atretic follicles. What make this dominant
foeto- maternal- barrier mechanism along withfollicle to attain these qualities among a vast pool of
caruncle formation, uterine milk formation and finallyfollicles needs further study. In coming 50 years one
union of cotyledous with caruncles has beenshall possibly understand and interlock a
photographically documented.pre-determined messenger system triggering
2.Introduction:dominance in one or few follicles destined to become
Second and 3rd generation animal biotechnologies asthe new offspring of that species. This system when
reviewed (Wani, 2005) are multiple ovulation,decoded shall offer new opportunities in controlling
embryo-transfer, preservation, cloning,ovulation both for contraception (women) or
micromanipulation splitting of embryos and nuclearaugmentation (animals). New genepool of dominant
transfer. The 4th Generation reproductivefollicles from dead high yielding animal ovaries would
technologies have advance beyond our imaginationhelp to propagate and multiply the elite.
and now we do have transgenic goats giving milk richOver stimulatory effect during superovulation could
in insulin. (Wani 2007). The stem cell technology,be avoided by use of antagonists, as dominant
embryonic cell culture, pronuclear micro-injection alongfollicles seem to evade suppression, thus follicular
with sperm-mediated, transgenesis have been in useselection will prevent excessive stimulation and cystic
and are precisely reviewed and discussed (Wanifollicles. Follicular fluid constituents containing occyte
2005, 2007).awaiting for biochemical signals to resume (meiosis )
The application of this advancement for diagnostic,growth and development to ensure timely and
therapeutic and economic uses especially its transferhealthy ovulation need more exploration (Lenton et
to human medicine or for field application in animalal., 1988). The specific signals triggering occyte release
industry needs further research and evaluation.might help in in vitro occyte maturation success rate.
The another fact which can be of importance is the11. Development of conceptus-in vitro foetus
number of cells per embryos. During first day theseThe lean meat production needs more studies on
may be two cells but after 8 days the cell numberdevelopment of conceptus. The prenatal
increases to 120 or more. It takes 32 hours for thedevelopment undergoes in three stages. The early
oocyst after fertilization to reach the two cellpregnancy signals, skeletal & nervous tissue growth,
embryo. Another 13 hours are needed to develop iton priority. During mid-gestation the hind and
into a four cell embryo. In another 15 hours 8 cellfore-limbs develop. During late gestation muscular
stages is reached. It is from here onwards that itdevelopment along with peripheral extremities
takes 30 hours for a embryo to be converted into aincluding hair develop. In order to increase lean meat
Morula. This has been one of the most critical periodsproduction, research in needed to investigate relations
of embryonic development in ovine. A genematicbetween hard and soft tissues. Maternal and foetal
diagram of various stages of follical maturation ofinteractions needs a probe. Some basic studies (Mufti,
oocytes development and further development has1996) indicated prospects of manipulating lean meat
been reported (Wani 2005a) figure from web site isproduction (Wani, 2001, 2002 a) by bio-stimulators
also show that the protein content after fertilizationduring late gestation, which may help, the production
of 16 day old embryo increased by 7500 times.of muscular lambs/kids at birth, besides, increasing
Morphologically the embryo size varies from sphericalbirth weight. More details have been described (Wani,
ovid to elongate after day 13th past coitus. New2001, 2002a) Fig.1-5). More studies in future are
protein synthesis per unit of embryo is maximumneeded to reveal the exact mechanism involved in
during 8-13th day old embryos. Similarlycritical transition of power control from maternal to
phosphorylation per unit of embryo is also ten timesembryonic genome. Application of recent techniques
more in 8 day old embryos than the later stages.of reverse transcription, PCR and others may reveal
Glucose and lactose production increased up to daythe details (Schultz et al., 1990).
16th and the maximum metabolic weight is up to12. Slaughter house follicle pool
14th day past coitus. For increased productiveA good number of our endangered species die where
synthesis, aminoacid requirements are made, throughclimatic conditions are hard and harsh. Under
production of allanic and glutonic acids by thetemperate climatic conditions dead bodies are
embryos. The matobolic products get rid of amines.entrapped in snow for long. It gives a hope to revive
The signal transduction from maternal to foetaltheir follicular pool. Our studies on resumption of life
controls have been discussed (Moris et al 2001).using follicles from slaughtered sheep and fertilizing
3. Dominant follicle dynamicsthem with epididymal semen was an pioneering
The new animal , products, medico-Veterinaryattempt in this direction (Wani, 1996) (Fig 6-8). The
packages, profitable genetic (trait) improved DNAprotein content of unfertilized ovum is around 100 mg
Chips, more resistance giving gene make ups shallin rabbit, 27 mg in mouse (Brinister, 1967, 1971). The
have a new role in future. For the next coming supersmall genetic material needs extensive analysis to
advanced technology driven century, we must beunveil vast informations in its codans and anticodans.
prepared to use the 4th generation technologies forFurther ovum maturation or resumption of meiosis is
animal Welfare and Protective mechanisms. Weinitiated during birth or shortly before birth and thus
thought and used Laparoscopy and ultrasonographythe pool of follicles remains fixed at birth. Therefore,
30 year ago (Wani et al, 1979, Wani 1981,1982),foetal ovary has to be the subject of further
which has now become a "buzz" word and furthermanipulations especially in view of its immunological
sophisticated and modernized by my students acrossinsensitivity (Guraya, 1985).
the world (Aggarwal, 2006, Wani, 2006). Our concept13. Gamete biosafety
of DNA finger printing of cashmere goats in 1990'sBacterial counts in semen in unprecedented numbers
(Khatlani et al, 1995) has now crossed the barriers ofeffect semen fertility (Kher, and Dholokia, 1985), The
technology advancement. Today, in these pages, wecontaminational hazards have increased due to
shall be presenting our own results onenvironmental pollution, water and air contamination.
1. Embryonic development, formation of cotyledons,Above all the development of resistance of known
blactocyst development ramification of vascularbateria and other micro-organism to antibiotics (Gupta
system, net working of blood vessels to form initialand Maurya, 1993). We have examined the semen of
placenta, their union and attachment processes. Weabout 40 bulls maintained at the Frozen semen bank,
shall describe morphological physiological,Rambirbag, Kashmir for bacterial loads in semen and
endocrinology, histochemical and receptor analysis totested antibiotic sensitivity (Koul, 2002).
support our observations. This is 5th generationPresence of bacteria in large numbers in semen,
reproductive technology base for development ofeffects its quality and fertility (Kher and Dholokia,
in-vitro-foeto models.1985). The source of contamination of semen vary
For 6th - 10th generation reproductive scientists wefrom inflammatory foci and lesions on penile
shall present theoretical hypothesis a vision -2050 inapparatus, contaminations on equipments, appliances,
the form of.diluters, extenders, air and laboratory environment.
2. Use of stem-cell, germ-cell and Nano- technologiesThese contamination hazards have increased with
for production of disease free, highly prolificenvironmental pollution. Many bacteria having
reproductive gametes, their preservation anddeveloped resistance to routine antibiotics used
conservation. The use of these and other molecular(Gupta and Maurya 1993) in semen extenders has
and new-generation DNA-related bio-diagnostics shallmade inseminations more critical and vulnerable. More
also be discussed.studies in this direction are needed to develop a
4. Uterine morphological changes:bio-safe and infection free germplasm pool of frozen
The early pregnancy uterine morphological land marksand fresh semen in future.
were described only externally per rectum in bovine14. Foeto-maternal interaction
(Zamznis, 1976) some of its significant features haveThe role of endometrial stromal cells during
been summarized in a booklet (Wani, 1986). Itpre-implantation stage needs further research. Some
describes easy palpable signs of early pregnancy instudies on ultrastructure of endometrium (Brinsfield et
bovine and compares its observations with equines,al., 1974) are still not sufficient to answer the
sheep and goats. Some of the earliest indications ofquestions. What is the role of immune cells and
pregnancy by physical examination were:i) Presenceendometrial cells in building of the immunological barrier
of corpus luteum of pregnancy early 15 dayto protect the foetus. Foetal biology is abarren field
post-coitusii) Asymmetry of uterine horns 30-35 daysof research in the world. After few initial steps by Dr.
post coitusiii) Fluctuation around 40-49 days in cattle.Moris Young in UK and D. Srivastava in India, only
Thereafter the advanced pregnancy signs like foetalscattered information is available on the subject
membrance feel and slips. Palpation of placentomes(Wani and Buchoo, 1990; Mufti, 1996) . Much is still to
and full foetal are known foetal membrane .be unveiled by 2050. The placental hormone influence
Various developments of foetal signs have beenmammary development and milk production of the
described (Wani, 1986) . The month wisedam. Foetal membranes serve as Chief source of
morphological assessment of foetus in sheep hasnutritive exchanges. The arrangement of cotyledons,
been reported (Mufti, 1995, Mufti et al, 1997) .caruncles, positioning of single and twin conceptus,
Various reviews reports and books now describeindicate complex mechanisms with common roots.
events in development of foetus (Wani, 2005, 2006,(Mufti et al., 2000) These mechanisms of
2007).foeto-maternal interactions and relationships
5. Development of conceptus-in vitro foetusemphasize proper foetal number diagnosis and
Pregnancy is an intimate association between mothercorresponding materno-nutritional management
and foetus. The protective covering on maternalstrategies.
caruncles and over wrap of foetal cotyledons with15. Nanotechnology:
Blastocyst membranes, transformed into foetalIn the proceeding pages we have seen the role of
membranes give the "Homograph" status to foetus.biotechnology in animal reproduction. The coming
The mechanism of ruminant uteri has been discussedgenerations will harvest the gains in the form of
(Gray et 2002). Its more recent findings andmore micron-level-accurate technology being replaced
attachments are the topic of one of our students.with nanogram-level-invisible technology- the
We have tried to univel many obscure mechanism onnanotechnology. Now even converging technologies
blastocyst formation, plancentation and developmentare shaped resulting from merger of Nano- science
of cotyledons. The protective mucin coverings overand Nanotechnology with biomedicine, bio-sciences,
uterine caruncles and their union with cotyledons hasbiotechnology, genetic engineering and information
been snaped.technology.
The internal changes have been correlated withThe cognitive sciences like Neuro- sciences,
biochemical, morphological and histochemical andcomputing, communication combined with
histoanatomic feature of the gravid and non-gravidnanotechnology may be so mystic and deterministic
uteri.that science shows will appear as "Majic shows" . This
6. Foeto-maternal interaction:new technology wave" may define our spiritualistic
The estrogen, progesterone in foetal and maternalwavelengths. Many unsolved or resolved facts on
blood have been estimated along with estrogenbirth and genetic make up shall send such messages
progesterone receptor concentrations in theas was known of Sagic saints, peers and Fakirs.
pregnancy and non pregnant states.The birth of a technology needs patience of public
Endometrial receptivity has been discussedand policy makers. In the past "Michael Farady" - the
(Huct-Hudson, et al 1989, Wani 1996, Wani, 2003,inventor of electric generator, was asked by the
205, 2006). Proliferation of uterine cells is influencedthen Chancellor of Exchequer, as to what use is the
by E2 and P4. These hormones have their receptorselectricity you are generating. He argues but no
in uteri called as E2 (ER) , P4 (PR) receptors (Lee andargument convinced the accountant. Finally, he
Demyo 2004) we have also investigated the samepromised him that the day will come when you can
and are being analysed. Our studies indicate certaintax it. Today a remote destination on this earth
changes which project a new mechanism ofdemands 24 hr electricity. They never argue its price,
foeto-maternal unions (Khatoon and Wani, 2007).but its availability as savoir to life be it medical,
Various growth factors described (Wani 2006) mayveterinary or any other field. Thus like Farady I
be helpful in future for invitro-foetal growth.profess and advocate experiments on use of
7. Reproductive managementnanotechnology in animal reproduction today. It may
The reproductive management strategies to enhancesound strange, but yes in my life I shall fore see a
meat production could safely be divided into tworole of nanotechnology in Animal reproduction.
kinds:i. Traditional management: Animal are still16. What is Nanotechnology:
managed under zero- input/ migratory /tribal orTechnology related to features of nanometer scale.
extensive management system. The application ofThus we will unveil gametes in minute details; sperm
above described methods will be limited. They mayhead colliding zona-pellucida shall be filmed. The radial
indirectly help in this system by better sire availability.ii.blast of cortical reaction shall be known. All chemical
Modern management: Zero-grazing, stall-fed ormessengers shall be unveiled at nano-level.
semi-intensive, commercial goat farming system mayThe shape of gamete, Zygote, embryo and foetal
use the above methods more and more to producedevelopment at nanolevel shall bring forth new
high quality germplasm. They may use variety ofadditions to our knowledge. The use of such
improved reproductive technique or reportedinformation through use of computer languages, both
(Wani,1996; Wani et al., 200a; Wani et al., 1998; Muftihard and soft shall make this knowledge dispensable
et al., 1997; Wani and Sahani, 1981; Wani et al., 1986,and useable at remote-corners of the Universe.
1987, 1988; Wani and Buchoo, 1991; Buchoo andCombing cognitive, mythical and mysterious happening
Wani, 1991; Wani, 1989, Wani, 1995; Wani, 1984a andwithin womb could be registered and translated via
b; Wani and Sahani, 1980a).nano-ultra-sonography.
8. Enhancement of fertilityThus futuristic view of nanotechnology will be
Desired fertility objectives have been discussednanographic follow of information and has been
(Wani, 2001). Increased prolificacy, early rebreeding,described ( Mordini, E, 2007).
safe/clean parturition, set-time animal crop, elite geneNanotechnology may allow us to send tiny nano
introduction are some of the desired fertilitymicroprocessors into the animal womb to send us
enhancement goals. The constraints in achievingsignals which we wish to know for prevention of
desired objectives in small ruminant livestock sectordiseases. The stem-cell-germ-cell technology combine
are the problems of inbreeding, reproductive losseswith Nanotechnology shall bring new hope and future
(Wani, et al., 1980; 1981; 1994), pre-pubertal mating,for the propapagation of Gene-technology-ETT- A-I
indiscriminate or illicit mating, venereal diseases,Combine. It may sound like sending a wave of spirit
nutritional and other stresses. These above referredto fertilize an "egg" - thus proving the "God Word in
factors reduce fertility status of our ruminantsQuran of creating the Chirst through mystic spirit.
especially under transhumane migratory systems.This and other convergence of known reproductive
These constraints mentioned could overcome bytechnologies are challenge to us in future
adopting enhancement strategies (Wani, 2001), whichNanaoparticels developed can be agents which would
include exchange of sires by tribal, Gujjar, Bakarwalsuse blood and carry durgs for curing disease at
and Chopans to reduce inbreeding. This could bemolecular levels. Thus a new mechanism of targeting
ensured through legislature or forced castrations andinfective agents of smaller dimension could be a
introduction of sires from outside the flock. Thepossibility.
pregnancy detection methods described (Wani, 1981)17. Stem-cell-Technology:
and later on used extensive in J&K under farmStem- cells are undifferentiated cells. The embryo at
condition (Wani et al., 1998; Wani, 1989) needsmorula stages have undifferentiated blastomeres.
adoption as a routine in each flock for better care ofThese cells can transform themselves into 200 or
offspring and dam.more cell type, which could be used to repair or
9. Corpora luteal biosensitivity.regenerate new desired cells. This advanced cell
Corpus luteum growth and development is the firstresearch may help diseased people like those
earliest pregnancy signal along with maternalsuffering from cancer, Alzheimer's disease syndrome,
recognition factors discussed (Wani, 1996). TheParkinsons disease and even paralysis.
corpus luteum development and receptivity to PGF2The stem cells are derived from 4-5 day old
alpha is now known. The ascending and descendingembryos or fertilized cells. The stem-cell-technology
corpora lutea are insensitive to PGF2 alpha. Whathas a new role to play in Animal reproduction.
makes them insensitive and what resurges theirFirstly, the stem-cell source could be pooled out of
sensitivity need exploration. May be in future, CLslaughter-house oocytes or from the vast pool of
insensitivity might have direct effects on survival ofembryos hatching out in many animal species.
the conceptus. Does conceptus make CL moreSecondly, the cell source could be obtained from
sensitive to PGF2 alpha? Or in other words, does thefoetal culture and if new-grown-immunoprotectant
gravid CL and non-gravid CL behave similarly orcell of foetus could help or provide germ-cell specific
differently to PGF2 alpha. Many such questionsto any particular organ, the repair of organs could be
vis-Ã -vis the ovarian morphology, uterinea new revolution.