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Nidaa Awaja Thesis.pdf (8.89 MB)

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THE ROLE OF SERINE/THREONINE PHOSPHATASES IN SPERM FUNCTION

Joudeh, Nidaa M
http://orcid.org/0000-0003-2574-2679
http://rave.ohiolink.edu/etdc/view?acc_num=kent1493594290482411

Abstract Details

2017, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
This thesis sheds light on the role of two main Ser/Thr phosphatases in sperm function: PP1¿2, and Calcineurin (PP2B). The results show for the first time that spermatogenesis in the testis can be supported by the somatic PP1 isoform PP1¿1, and that the unique male germ cell phosphatase “PP1¿2” has probably evolved in mammals along with the evolution of the mammalian epididymis for the sole purpose of supporting sperm epididymal maturation. We suggest that calcineurin has high activity in caput sperm due to the high levels of intracellular calcium. And that the effect of high calcium levels along with high phosphatase activity in caput sperm, have an inhibitory effect on sperm motility, opposing the effect of calcium on motility during sperm hyperactivation in the female reproductive tract. We propose that calcium signaling in sperm function has a biphasic role depending on which calcium dependent proteins are selectively activated at each developmental stage of the sperm journey. Calcieurin may also have a role in regulating mitochondrial activity. A shift in energy production pathways and substrate utilization occurs during sperm transition from the caput to the cauda epididymis, and calcineurin is believed to play a role in this process. With PP1¿2 shown to be irreplaceable by PP1¿1 during sperm epididymal maturation, the following step would be comparing the phosphoproteome of PP1¿2 bearing sperm with those of PP1¿1 bearing sperm. A wide phosphoproteome analysis will reveal the specific substrates of PP1¿2 that PP1¿1 are unable to dephosphorylate, highlighting proteins with an essential role in epididymal maturation and sperm motility regulation. There is a possibility that the phenotype of PP1¿1 rescue males is caused by the effect of the transgenes incorporation into a random region 145 of the mouse genome. The only way to test this hypothesis would be the generation of a new transgenic model using a gene knock-in technique, where the endogenous promoters function will be maintained, and there will be no random incorporation of genetic material into the genome. If the results of that new transgenic model support our data, then only we can confirm our conclusion. There is strong evidence that calcineurin has a role in mitochondrial energy production and activity. The following step would be analyzing PPP3R2 KO males for additional mitochondrial function parameters, such as oxygen consumption or measurement of a number of mitochondrial enzyme activities. Scanning electron microscopy can be performed to look for any mitochondrial elongation or fusion.
Srinivasan Vijayaraghavan, Dr. (Advisor)
Douglas Kline, Dr. (Committee Member)
Jennifer Marcinkiewicz, Dr. (Committee Member)
Fayez Safadi, Dr. (Committee Member)
Soumitra Basu (Other)
Biology
Spermatogenesis; Sperm function; Male reproduction

Recommended Citations

Citations

  • Joudeh, N. M. (2017). THE ROLE OF SERINE/THREONINE PHOSPHATASES IN SPERM FUNCTION [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1493594290482411

    APA Style (7th edition)

  • Joudeh, Nidaa. THE ROLE OF SERINE/THREONINE PHOSPHATASES IN SPERM FUNCTION. 2017. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1493594290482411.

    MLA Style (8th edition)

  • Joudeh, Nidaa. "THE ROLE OF SERINE/THREONINE PHOSPHATASES IN SPERM FUNCTION." Doctoral dissertation, Kent State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1493594290482411

    Chicago Manual of Style (17th edition)

kent1493594290482411
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This open access ETD is published by Kent State University and OhioLINK.