Can sperm protamine deficiency induce sperm premature chromosomal condensation?

Abstract

Sperm premature chromatin condensation (PCC) has been considered as the second cause of failed fertilization post-intracytoplasmic sperm injection (post-ICSI). Cytoplasmic factors, including oocyte cytoplasmic immaturity have been suggested to induce PCC sperm. However, recent studies suggest that sperm chromatin anomaly might also lead to PCC sperm. During this study, human sperm from infertile patients with protamine deficiency or with adequate amount of protamine assessed by chromomycin A3 were injected into metaphase II mouse oocyte, treated with colcemid. Chromatin analysis was carried out on the injected oocyte. The results of this study show that contrary to the percentage of intact sperm, percentage of PCC sperm was significantly higher in oocytes injected with protamine deficient sperm (36.43 +/- 4.46) compared to oocytes injected with sperm with an adequate amount of protamine (11.99 +/- 3.54, P < 0.001). A significant correlation was also observed between percentage of PCC sperm and protamine deficiency (r = 0.46, P = 0.004). Therefore, it can be suggested that oocytes injected with protamine deficient sperm have a higher chance of forming PCC sperm and may result in failed fertilization post-ICSI.

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“…According to the results of our study, it seems that one of the important reasons which can describe idiopathic infertility and fertilization failure in asthenosperm patients is PCC induction. Sperm protamine deficiency could be one of the factors that make sperm prone to PCC [1,13]. As it was mentioned before, protamines in sperms undergo oxidation in epididymis which leads to sperm nucleus stability.…”

“…Sperm decondensing activity is maximal in mature, metaphase II oocytes, but minimal or absent in immature, germinal vesicle (GV) oocytes [2]. Immature cytoplasms are believed to make sperms susceptible to high incidence of PCC following the insemination because these immature oocytes are unable to undergo oocyte activation [1]. However, it is already known that PCC formation is affected by so many factors both for oocytes and sperm abnormalities.…”

“…Disulfide bonds reduction, which is necessary for reactivation of the sperm nucleus, begins shortly after the sperm nucleus makes contact with the ooplasm. Little is known about the oocyte factors involved in protamine disulfide bond reduction and subsequent dispersion of sperm chromatin during fertilization [1,2,13]. Perreault et al (1987) [14] reported the hamster sperm nuclei treated by Dithiothreitol (DTT) decondensed more rapidly when microinjected into hamster oocytes.…”

“…During maturation of sperm in the epididymis these protamine sulfhydryls undergo oxidation, resulting in further stabilization of the sperm nucleus [2]. Following penetration of sperm into an oocyte; oocyte activation is triggered, resulting in completion of meiosis and formation of both male and female pronuclei [1]. Protamine must be reduced during fertilization so that reactivation of the sperm nucleus will proceed.…”

“…When a cell, whose chromosomes are in metaphase, is fused with an inter-phase cell, the nuclear membrane of the cell in interphase dissolves and its chromatin condenses. This phenomenon is called premature chromosomal condensation [1]. In mammalian sperm, protamines serve to stabilize the nucleus and maintain the DNA in a transcriptionally inert condition.…”