Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment

Junaid Kashir; Bhavesh V. Mistry; Lujain BuSaleh; Reema Abu-Dawas; Michail Nomikos; Ahmed Ajlan; Raed Abu-Dawud; Nadya AlYacoub; Saad AlHassan; F. Anthony Lai; Abdullah M. Assiri; Serdar Coskun

doi:10.1111/andr.12796

Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment

Junaid Kashir, Bhavesh V. Mistry, Lujain BuSaleh, Reema Abu-Dawas, Michail Nomikos, Ahmed Ajlan, Raed Abu-Dawud, Nadya AlYacoub, Saad AlHassan, F. Anthony Lai, Abdullah M. Assiri, Serdar Coskun

Biological Sciences

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Background: Oocyte activation is driven by intracellular calcium (Ca²⁺) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability. Materials and Methods: PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 × 10⁶ spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. Results and Discussion: Four distinct PLCζ patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal + equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLCζ. Conclusions: PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.

Original language	British English
Pages (from-to)	1143-1159
Number of pages	17
Journal	Andrology
Volume	8
Issue number	5
DOIs	https://doi.org/10.1111/andr.12796
State	Published - 1 Sep 2020

Keywords

fertilisation
male infertility
oocyte activation
phospholipase C zeta (PLCzeta)
spermatozoa

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10.1111/andr.12796

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Kashir, J., Mistry, B. V., BuSaleh, L., Abu-Dawas, R., Nomikos, M., Ajlan, A., Abu-Dawud, R., AlYacoub, N., AlHassan, S., Lai, F. A., Assiri, A. M., & Coskun, S. (2020). Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment. Andrology, 8(5), 1143-1159. https://doi.org/10.1111/andr.12796

@article{0becafc6c7b748709299f3f0dba9bf48,

title = "Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment",

abstract = "Background: Oocyte activation is driven by intracellular calcium (Ca2+) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability. Materials and Methods: PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 × 106 spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. Results and Discussion: Four distinct PLCζ patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal + equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLCζ. Conclusions: PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.",

keywords = "fertilisation, male infertility, oocyte activation, phospholipase C zeta (PLCzeta), spermatozoa",

author = "Junaid Kashir and Mistry, {Bhavesh V.} and Lujain BuSaleh and Reema Abu-Dawas and Michail Nomikos and Ahmed Ajlan and Raed Abu-Dawud and Nadya AlYacoub and Saad AlHassan and Lai, {F. Anthony} and Assiri, {Abdullah M.} and Serdar Coskun",

note = "Funding Information: JK was supported by a Healthcare Research Fellowship Award (HF-14-16) made by Health and Care Research Wales (HCRW). This study was also supported by a National Science, Technology and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST) to JK, AMA and FAL. Some of the work described herein was performed by LB and R AbuDawas as part of their graduate research projects. The authors thank Dr Evangelia Livaniou and Dr Vyronia Vassilakopoulou of the National Center for Scientific Research {\textquoteleft}Demokritos' (Athens, Greece) for their assistance in generating the EF polyclonal antibody against PLCζ, Dr Peter MB Cahusac of Alfaisal University (Riyadh, Kingdom of Saudi Arabia) for invaluable discussion and assistance regarding statistical analyses, and Mr Faisal Alotaibi and the Research Centre Administration at the KFSHRC (Riyadh Kingdom of Saudi Arabia) for their invaluable efforts in assisting with experimental logistics. Funding Information: JK was supported by a Healthcare Research Fellowship Award (HF‐14‐16) made by Health and Care Research Wales (HCRW). This study was also supported by a National Science, Technology and Innovation plan (NSTIP) project grant (15‐MED4186‐20) awarded by the King Abdulaziz City for Science and Technology (KACST) to JK, AMA and FAL. Publisher Copyright: {\textcopyright} 2020 American Society of Andrology and European Academy of Andrology",

year = "2020",

month = sep,

day = "1",

doi = "10.1111/andr.12796",

language = "British English",

volume = "8",

pages = "1143--1159",

journal = "Andrology",

issn = "2047-2919",

publisher = "John Wiley & Sons Inc.",

number = "5",

}

TY - JOUR

T1 - Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment

AU - Kashir, Junaid

AU - Mistry, Bhavesh V.

AU - BuSaleh, Lujain

AU - Abu-Dawas, Reema

AU - Nomikos, Michail

AU - Ajlan, Ahmed

AU - Abu-Dawud, Raed

AU - AlYacoub, Nadya

AU - AlHassan, Saad

AU - Lai, F. Anthony

AU - Assiri, Abdullah M.

AU - Coskun, Serdar

N1 - Funding Information: JK was supported by a Healthcare Research Fellowship Award (HF-14-16) made by Health and Care Research Wales (HCRW). This study was also supported by a National Science, Technology and Innovation plan (NSTIP) project grant (15-MED4186-20) awarded by the King Abdulaziz City for Science and Technology (KACST) to JK, AMA and FAL. Some of the work described herein was performed by LB and R AbuDawas as part of their graduate research projects. The authors thank Dr Evangelia Livaniou and Dr Vyronia Vassilakopoulou of the National Center for Scientific Research ‘Demokritos' (Athens, Greece) for their assistance in generating the EF polyclonal antibody against PLCζ, Dr Peter MB Cahusac of Alfaisal University (Riyadh, Kingdom of Saudi Arabia) for invaluable discussion and assistance regarding statistical analyses, and Mr Faisal Alotaibi and the Research Centre Administration at the KFSHRC (Riyadh Kingdom of Saudi Arabia) for their invaluable efforts in assisting with experimental logistics. Funding Information: JK was supported by a Healthcare Research Fellowship Award (HF‐14‐16) made by Health and Care Research Wales (HCRW). This study was also supported by a National Science, Technology and Innovation plan (NSTIP) project grant (15‐MED4186‐20) awarded by the King Abdulaziz City for Science and Technology (KACST) to JK, AMA and FAL. Publisher Copyright: © 2020 American Society of Andrology and European Academy of Andrology

PY - 2020/9/1

Y1 - 2020/9/1

N2 - Background: Oocyte activation is driven by intracellular calcium (Ca2+) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability. Materials and Methods: PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 × 106 spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. Results and Discussion: Four distinct PLCζ patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal + equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLCζ. Conclusions: PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.

AB - Background: Oocyte activation is driven by intracellular calcium (Ca2+) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability. Materials and Methods: PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability. Male recruitment criteria required a minimum sperm count of 5 × 106 spermatozoa/mL, while all female patients included in this study yielded at least five oocytes for treatment. Sperm count, motility and semen volume were recorded according to standard WHO reference guidelines and correlated with PLCζ profiles examined via immunoblotting and immunofluorescence. Appropriate fertility treatments were performed following routine clinical standard operating protocols, and fertilisation success determined by successful observation of second polar body extrusion. Results and Discussion: Four distinct PLCζ patterns were observed at the equatorial, acrosomal + equatorial regions of the sperm head, alongside a dispersed pattern, and a population of spermatozoa without any PLCζ. Acrosomal + equatorial PLCζ correlated most to sperm health, while dispersed PLCζ correlated to decreased sperm viability. Total levels of PLCζ exhibited significant correlations with sperm parameters. PLCζ variance corresponded to reduced sperm health, potentially underlying cases of male sub-fertility and increasing male age. Finally, significantly higher levels of PLCζ were exhibited by cases of fertilisation success, alongside higher proportions of Ac + Eq, and lower levels of dispersed PLCζ. Conclusions: PLCζ potentially represents a biomarker of sperm health, and fertilisation capacity in general cases of patients seeking fertility treatment, and not just cases of repeated fertilisation. Further focused investigations are required with larger cohorts to examine the full clinical potential of PLCζ.

KW - fertilisation

KW - male infertility

KW - oocyte activation

KW - phospholipase C zeta (PLCzeta)

KW - spermatozoa

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U2 - 10.1111/andr.12796

DO - 10.1111/andr.12796

M3 - Article

C2 - 32298520

AN - SCOPUS:85085054658

SN - 2047-2919

VL - 8

SP - 1143

EP - 1159

JO - Andrology

JF - Andrology

IS - 5

ER -

Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment

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