Manchette-acrosome disorders during spermiogenesis and low efficiency of seminiferous tubules in hypercholesterolemic rabbit model

Abstract

Hypercholesterolemia is a marker for several adult chronic diseases. Recently we demonstrated that sub/infertility is also associated to Hypercholesterolemia in rabbits. Seminal alterations included: abnormal sperm morphology, decreased sperm number and declined percentage of motile sperm, among others. In this work, our objective was to evaluate the effects of hypercholesterolemia on testicular efficiency and spermiogenesis, as the latter are directly related to sperm number and morphology respectively. Tubular efficiency was determined by comparing total number of spermatogenic cells with each cell type within the proliferation/differentiation compartments. We found lower testicular efficiency related to both a decrease in spermatogonial cells and an increase in germ cell apoptosis in hypercholesterolemic rabbits. On the other hand, spermiogenesis–the last step of spermatogenesis involved in sperm shaping–was detaily analyzed, particularly the acrosome-nucleus-manchette complex. The manchette is a microtubular-based temporary structure responsible in sperm cell elongation. We analyzed the contribution of actin filaments and raft microdomains in the arrangement of the manchette. Under fluorescence microscopy, spermatocyte to sperm cell development was followed in cells isolated from V to VIII tubular stages. In cells from hypercholesterolemic rabbits, abnormal development of acrosome, nucleus and inaccurate tail implantation were associated with actin–alpha-tubulin–GM1 sphingolipid altered distribution. Morphological alterations were also observed at electron microscopy. We demonstrated for the first time that GM1-enriched microdomains together with actin filaments and microtubules are involved in allowing the correct anchoring of the manchette complex. In conclusion, cholesterol enriched diets promote male fertility alterations by affecting critical steps in sperm development: spermatogenesis and spermiogenesis. It was also demonstrated that hypercholesterolemic rabbit model is a useful tool to study serum cholesterol increment linked to sub/infertility.

Cholesterol: A Gatekeeper of Male Fertility?

“…It has been shown that administration of tamoxifen, used in the treatment of idiopathic male infertility to HFD rabbits partially restored sperm motility, but further decreased morphology and increased spontaneous acrosome reaction ( 136 ). It has also been shown that hyper-cholesterolemic rabbits present lower testicular efficiency related to both a decrease in spermatogonial cells and an increase in germ cell apoptosis ( 137 ). On the other hand, spermiogenesis, which is the last step of spermatogenesis, was also affected in these animals.…”

Influence of hyperproteinemia on reproductive development in an invertebrate model

“…Metabolic abnormalities of the circulatory system have been reported to have significant adverse effects on reproductive development. Hypercholesterolemia directly affects fertilization by inducing germ cell apoptosis, worsening Leydig and Sertoli cell secretory functions, reducing sperm production and increasing sperm morphological abnormalities in rabbits [22][23][24] . Hypercholesterolemia and hyperlipidemia during pregnancy inhibited blastocyst development and altered oocyte metabolism, leading to defects in fetal glucose supply and affecting fetal vascular development [25][26][27] .…”

Manchette-acrosome disorders and testicular efficiency decline observed in hypercholesterolemic rabbits are recovered with olive oil enriched diet

“…In our previous work, we reported the localization of actin, tubulin and ganglioside GM1 in the elongation area [ 20 ]. This particular localization could indicate that microtubules interact with a network of actin filaments that may be associated with membrane microdomains in the elongation area.…”

“…Testicles generate less number of ejaculated sperm cells during spermatogenesis under high-fat diet but the sperm number is recovered when olive oil is added to diet [ 6 ]. The sperm number reduction is associated with a testicular efficiency decline in hypercholesterolemic rabbits[ 20 ]. However, testicular efficiency under the administration of olive oil remains unknown until now.…”