Evolution of Hemoglobin Genes in a Subterranean Rodent Species (Lasiopodomys mandarinus)

The Mandarin vole (Lasiopodomys mandarinus), a typical subterranean rodent, has undergone hematological adaptations to tolerate the hypoxic/hypercapnic underground environment. Hemoglobin (Hb) genes encode respiratory proteins functioning principally in oxygen binding and transport to various tissues and organs. To investigate the evolution of α- and β-hemoglobin (Hb) in subterranean rodent species, we sequenced Hb genes of the Mandarin vole and the related aboveground Brandt’s vole (L. brandtii). Sequencing showed that in both voles, α-globin was encoded by a cluster of five functional genes in the following linkage order: HBZ, HBA-T1, HBQ-T1, HBA-T2, and HBQ-T2; among these, HBQ-T2 is a pseudogene in both voles. The β-globin gene cluster in both voles also included five functional genes in the following linkage order: HBE, HBE/HBG, HBG, HBB-T1, and HBB-T2. Phylogenetic analysis revealed that the Mandarin vole underwent convergent evolution with its related aboveground species (Brandt’s vole) but not with other subterranean rodent species. Selection pressure analyses revealed that α- and β-globin genes are under strong purifying selection (ω < 1), and branch-site analyses identified positive selection sites on HBAT-T1 and HBB-T1 in different subterranean rodent species. This suggests that the adaptive evolution of these genes enhanced the ability of Hb to store and transport oxygen in subterranean rodent species. Our findings highlight the critical roles of Hb genes in the evolution of hypoxia tolerance in subterranean rodent species.

Complex Structure of Lasiopodomys mandarinus vinogradovi Sex Chromosomes, Sex Determination, and Intraspecific Autosomal Polymorphism

The mandarin vole, Lasiopodomys mandarinus, is one of the most intriguing species among mammals with non-XX/XY sex chromosome system. It combines polymorphism in diploid chromosome numbers, variation in the morphology of autosomes, heteromorphism of X chromosomes, and several sex chromosome systems the origin of which remains unexplained. Here we elucidate the sex determination system in Lasiopodomys mandarinus vinogradovi using extensive karyotyping, crossbreeding experiments, molecular cytogenetic methods, and single chromosome DNA sequencing. Among 205 karyotyped voles, one male and three female combinations of sex chromosomes were revealed. The chromosome segregation pattern and karyomorph-related reproductive performances suggested an aberrant sex determination with almost half of the females carrying neo-X/neo-Y combination. The comparative chromosome painting strongly supported this proposition and revealed the mandarin vole sex chromosome systems originated due to at least two de novo autosomal translocations onto the ancestral X chromosome. The polymorphism in autosome 2 was not related to sex chromosome variability and was proved to result from pericentric inversions. Sequencing of microdissection derived of sex chromosomes allowed the determination of the coordinates for syntenic regions but did not reveal any Y-specific sequences. Several possible sex determination mechanisms as well as interpopulation karyological differences are discussed.

Increased anxiety and decreased sociability in adulthood following paternal deprivation involve oxytocin in the mPFC

Early adverse experiences often have devastating consequences on adult emotional and social behavior. However, whether paternal deprivation (PD) during the pre-weaning period affects brain and behavioral development remains unexplored in socially mandarin vole (Microtus mandarinus). We found that PD increased anxiety-like behavior and attenuated social preference in adult males and females; decreased prelimbic cortex OT-immunoreactive fibers and paraventricular nucleus OT positive neurons; reduced levels of medial prefrontal cortex (mPFC) OT receptor protein in females and OT receptor and V1a receptor protein in males. Intra-prelimbic cortical OT injections reversed anxiety-like behavior and social preferences affected by PD, whereas injections of OT and OT receptor antagonist blocked this reversal. These findings demonstrate that PD leads to increased anxiety-like behavior and attenuated social preferences with involvement of the mPFC OT system. The prelimbic cortex OT system may be an important target for the treatment of disorders related to early adverse experiences.

Effects of Tripterygium wilfordii multiglycosides on sex hormones and receptors in mandarin vole Leydig cells

Multiglycosides ofTripterygium wilfordii(GTW) have been found to exhibit reversible antifertility effects through complex mechanisms. The positive expression of sex hormones and receptors in Leydig cells were investigated following GTW treatment to determine the impact of GTW on male mandarin vole (Microtus mandarinus) fertility. Compared to the control group, body weight, testis and epididymis weight were not affected by GTW, but the number of sperm sharply declined. There were significant decreases in the thickness of seminifeous epithelium and epididymal epithelium, and the diameter of seminiferous tubules. The expression of estrogen receptor alpha (ERα) in Leydig cells significantly decreased and estradiol (E) expression significantly increased. Testosterone (T) and androgen receptor (AR) expression were not affected. These results show that GTW may impair fertility in male mandarin voles via interference with spermatogenesis. This may be associated with an alteration in estrogen activation rather than suppression of T and AR in Leydig cells and suggests the estrogen system of Leydig cells is of major importance for the GTW’s antifertility effects.