Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals

Abstract

In mammals, motility and fertilizing ability of spermatozoa develop during their passage through the epididymis. After ejaculation, sperm undergo capacitation and hyperactivation in the female reproductive tract-a motility transition that is required for sperm penetration of the egg. Both epididymal initiation of sperm motility and hyperactivation are essential for male fertility. Motility initiation in the epididymis and sperm hyperactivation involve changes in metabolism, cAMP (cyclic adenosine monophosphate), calcium and pH acting through protein kinases and phosphatases. Despite this knowledge, we still do not understand, in biochemical terms, how sperm acquire motility in the epididymis and how motility is altered in the female reproductive tract. Recent data show that the sperm specific protein phosphatase PP1γ2, glycogen synthase kinase 3 (GSK3), and the calcium regulated phosphatase calcineurin (PP2B), are involved in epididymal sperm maturation. The protein phosphatase PP1γ2 is present only in testis and sperm in mammals. PP1γ2 has a isoform-specific requirement for normal function of mammalian sperm. Sperm PP1γ2 is regulated by three proteinsinhibitor 2, inhibitor 3 and SDS22. Changes in phosphorylation of these three inhibitors and their binding to PP1γ2 are involved in initiation and activation of sperm motility. The inhibitors are phosphorylated by protein kinases, one of which is GSK3. The isoform GSK3α is essential for epididymal sperm maturation and fertility. Calcium levels dramatically decrease during sperm maturation and initiation of motility suggesting that the calcium activated sperm phosphatase (PP2B) activity also decreases. Loss of PP2B results in male infertility due to impaired sperm maturation in the epididymis. Thus the three signaling enzymes PP1γ2, GSK3, and PP2B along with the documented PKA (protein kinase A) have key roles in sperm maturation and hyperactivation. Significantly, all these four signaling enzymes are present as specific isoforms only in placental mammals, a testimony to their essential roles in the unique aspects of sperm function in mammals. These findings should lead to a better biochemical understanding of the basis of male infertility and should lead to novel approaches to a male contraception and managed reproduction.

The sodium/proton exchanger SLC9C1 (sNHE) is essential for human sperm motility and fertility

“…Among the changes occurring within the female genital tract (i.e. capacitation), were described alkalinization of the cytoplasm, membrane hyperpolarization and protein phosphorylation cascades induced by the activation of soluble adenylate cyclase (sAC) and protein kinase A (PKA), which specifically target flagellar components required for sperm fertilization potential 16 …”

Ethanolic extract of Dutch eggplants (Solanum betaceum) protects spermatozoa motility exposed to lead acetate

“…Spermatozoa require several enzymes and receptors for their movement. 32 The results of this study showed that the administration of ethanolic S. betaceum extracts significantly affected the total motility of spermatozoa. The highest percentage increase in the mean total motility is shown by giving the highest dose of 400 mg/kg body weight.…”

Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice

“…In addition to the integrity of the fibrous sheath, sperm motility also depends directly on cAMP and calcium functioning. cAMP has been reported as an essential element in the initiation of sperm motility, as it can activate tyrosine kinase and increase the flagellar beat frequency [ 24 ]. Past studies have thoroughly investigated the role of calcium in sperm motility, indicating that increasing Ca 2+ concentration can raise the sperm glycolysis level and promote motility hyperactivation [ 25 ].…”