**11. Differentiation in meiotic events of sperm and oocyte in** *C. elegans*

In oocyte, synaptonemal complex (SC) is formed along the lateral and central axis. In sperms condensation plate is formed after diplotene. Formation of karyosomes, [the aggregation of chromosomes] is characterised in both oocytes and sperms of *C. elegans* and other mammals and referred as karyosome stage in *C. elegans*. The meiotic process mainly differs in microtubule dynamics. In oocytes chromosome dependent spindle formation is necessary for chromosome segregation, where as in case of sperms centrioles are present. So, the spindle formation is mediated by centrioles.

There are some of the kinetochore differences observed in oocytes and sperms. In sperms, outer kinetochore proteins attract the inner proteins. CENP –c is present in spermatocytes and CENP- A is present in oocytes. Some of the kinases like AIR-2 is present in spermatocytes and PLK-1 is found in oocytes. SYP-1 is necessary protein of central element in SC and recruits AIR-2. Mutation in SYP-1 protein leads to random distribution of metaphase bivalents. Some of the kinases like AIR-2 phosphorylates Rec-8 protein which is required for cohesion of sister chromatids. Cytokinesis after meiosis −1 is incomplete in both sperms and oocyte without any necessity for re condensation of chromatin after diplotene.

### **12. Oxidative potential in testes and epididymis is required for spermiogenesis**

GPRX 4 and PXRX4 are the two enzymes which are mainly required for compaction of chromatin in sperm mainly by sulfoxidation of protamines attached to DNA. PXRX4 is necessary for condensation in testes where as GPRX4 is specifically in epididymis. Hydrogen peroxide acts as signalling molecule and causes phosphorylation of tyrosine molecules in the receptor, necessary for proliferation of sperm cells [31]. Abnormal signalling by hydrogen peroxide leads to sperm cancer which can be avoided by reduction of H2O2 by enzymes like SOD and catalase. Totally GPRX4 and PXRX4 is necessary for nuclear stability, condensation and spermiogenesis.

### **13. Factors responsible for condensation and decondensation of chromatin**

Zinc is well known for maintenance of membrane stability and found to be present in seminal plasma. It is decreased during penetration of sperm in to the female reproductive tract and decrease of zinc causes premature decondensation of chromatin as it destabilises the sperm plasma membrane. Albumin also binds to zinc and accelerates decondensation. In humans heparin is involved in decondensation of chromatin. Zinc also binds to free thiols and increases stability of chromatin, necessary for reducing disulfide bonds and accelerating the reaction (**Figure 4**).

Few of the recent techniques used for measurement of DNA condensation and decondensation include using of TPM motions and energy. Condensation of DNA leads to decrease in length as protamines are organised as toroids. Where as decondensed chromatin is more in length as protamines are replaced by histones. Differences in motions of the DNA attached to the coverslip is captured and ultimately the difference in energy. Positive relation is seen between the persons with premature decondensation in DNA and infertility and DNA damage based on the studies in human subjects. Sperm fluorescent in situ hybridisation is other technique used to assess the relation between sperm DNA [32] condensation and abnormalities of head.

**Figure 4.** *Percentage of cells with DNA fragmentation using different techniques of assessment.*

### **14. Assisted reproductive technologies required for success of reproductive outcome**

ICSI and IVF are the techniques used in assisted reproductive technology, in which ICSI resulted in more percentage of PCC (pre mature condensation of

**55**

mitochondria.

formation.

**15. Summary**

maintain genome integrity in offspring.

**16. Metosartan acts as genotoxic agent of testes**

*Understanding the Epigenetic Modifications in Sperm Genome*

chromatin) compared to IVF. It is mainly due to lack of activation of oocytes. and Pre mature condensation is due to the condensing factors released from the unactivated oocytes without affecting the sperms with intact plasma membrane. The main failure for ICSI is due to the injection of whole sperm in to oocytes. Fusion of oocytes and sperm membranes activates the oocytes lacking of which, was one of the main drawback seen in ICSI [33, 34]. Even damage to sperm membrane is

Expression of decondensing factors like MPF is transient, as temporal expression is seen whereas in later stages sperm dependent factor SDF is mainly involved in activation of oocytes causing further decondensation of sperm chromatin. IVF does not include steps that cause damage to sperm DNA [35] and prevention of oocyte activation. The low rate of success is due to many reasons. One of the main reasons is DNA damage in spermatozoa. ART involves use of techniques which does not involve natural fertilisation. So, there may be chance of DNA damage. Sperm DNA lacks repair proteins that aids in protection against DNA damage. So, oocyte acts as source for repair proteins as it is active in gene expression. If the DNA damage overwhelms the oocyte capacity it leads to genetic aberrations in future generations. So, instead of choosing a single technique one has to get through the different

When compared with high DNA damage the rate of pregnancy is more in case of IVF compared to ICSI. But in case of miss carriages rate it is more in ICSI compared to IVF. The reason is the post paternal factors play a pivotal role in repair of damage, and use of testicular sperm is helpful in ICSI if there is repeated miss carriages and low pregnancy rates. The assessment of sperm genome integrity is limited because different techniques used gives different outcomes. But SCSA is useful to assess testicular sperm for good outcome of results. Finally the outcome of ICSI cannot be predicted with respect to DNA condensation in both testicular sperm collected by biopsy and ejaculated spermatozoa in terms of pregnancy, cleavage and embryo

Condensation of sperm genome was necessary for maintaining genome integrity by transition of histones by transition proteins which in turn by protamines. These proteins undergo some of PTM namely phosphorylation, Acetylation, poly ADP ribosylation and methylation. Further stability in interaction between DNA and protamine involves addition of disulfide bonds to form interlinking protamines. Dihydrotestosterone acts as hydrogen donor and acceptor in testes and necessary for maturation of sperms. Zinc acts as stabiliser of Genome through its interaction with protamines and toxicity due to metals responsible for male infertility [36] is due to interaction of these metal ions with protamines. So, safe ART is required to

Metosartan induces endometrial carcinoma in testes and causes changes in chromatin dynamics and causes prematurity in sperms. It causes competitive and non competitive inhibition of RNase present in male Wistar rats. It also decreases the sperm count, motility and induces abnormalities in sperm structure. It also causes apoptosis in both testes and sperm by increasing the permeability of

*DOI: http://dx.doi.org/10.5772/intechopen.88506*

another draw back seen with this technique.

techniques that help in selecting the single top spermatozoa.

### *Understanding the Epigenetic Modifications in Sperm Genome DOI: http://dx.doi.org/10.5772/intechopen.88506*

chromatin) compared to IVF. It is mainly due to lack of activation of oocytes. and Pre mature condensation is due to the condensing factors released from the unactivated oocytes without affecting the sperms with intact plasma membrane. The main failure for ICSI is due to the injection of whole sperm in to oocytes. Fusion of oocytes and sperm membranes activates the oocytes lacking of which, was one of the main drawback seen in ICSI [33, 34]. Even damage to sperm membrane is another draw back seen with this technique.

Expression of decondensing factors like MPF is transient, as temporal expression is seen whereas in later stages sperm dependent factor SDF is mainly involved in activation of oocytes causing further decondensation of sperm chromatin. IVF does not include steps that cause damage to sperm DNA [35] and prevention of oocyte activation. The low rate of success is due to many reasons. One of the main reasons is DNA damage in spermatozoa. ART involves use of techniques which does not involve natural fertilisation. So, there may be chance of DNA damage. Sperm DNA lacks repair proteins that aids in protection against DNA damage. So, oocyte acts as source for repair proteins as it is active in gene expression. If the DNA damage overwhelms the oocyte capacity it leads to genetic aberrations in future generations. So, instead of choosing a single technique one has to get through the different techniques that help in selecting the single top spermatozoa.

When compared with high DNA damage the rate of pregnancy is more in case of IVF compared to ICSI. But in case of miss carriages rate it is more in ICSI compared to IVF. The reason is the post paternal factors play a pivotal role in repair of damage, and use of testicular sperm is helpful in ICSI if there is repeated miss carriages and low pregnancy rates. The assessment of sperm genome integrity is limited because different techniques used gives different outcomes. But SCSA is useful to assess testicular sperm for good outcome of results. Finally the outcome of ICSI cannot be predicted with respect to DNA condensation in both testicular sperm collected by biopsy and ejaculated spermatozoa in terms of pregnancy, cleavage and embryo formation.
