Reproductive injury in male BALB/c mice infected with Neospora caninum

Abstract

Background Neospora caninum is one of the main causes of abortion in pregnant animals. However, N. caninum-induced reproductive injury in male mice is still unclear. Methods Male BALB/c mice were infected with a bovine isolate of N. caninum, and the organ coefficients of the testis and epididymis were measured. Lesions in the testis and epididymis were observed by light microscopy and transmission electron microscopy. Expression of the spermatogenic cell apoptosis-related proteins p53 and caspase-3 was detected by western blot. The expression of spermatogenesis-related genes in the testis was detected by reverse transcription-PCR. Sperm morphology and motility were observed. The levels of nitric oxide (NO) and antisperm antibody (AsAb) in the testicular homogenates and hormones in the serum were detected by enzyme-linked immunosorbent assay. The reproductive capacity of the male mice was detected using a reproduction test. Results The organ coefficients of the testis and epididymis of the experimental group were significantly downregulated. Light microscopy examination revealed that the spermatogenic cells of the testis were arranged in a disordered manner, and the number was reduced. The number of sperm in the epididymal lumen was significantly reduced, and the cytoplasm exhibited vacuolation and degeneration. Ultrastructural studies revealed that the cells of the testis and epididymis tissues showed varying degrees of disease. The level of p53 and caspase-3 expression in the testis was significantly upregulated. The expression of the testicular spermatogenesis-related genes Herc4, Ipo11 and Mrto4 were strongly downregulated. Observation of sperm by microscopic examination revealed significantly reduced sperm density and sperm motility, and the number of sperm deformities was significantly increased. The level of NO and AsAb was significantly increased. The levels of luteinizing hormone, follicle-stimulating hormone and gonadotropin-releasing hormone were significantly upregulated, whereas the levels of testosterone, thyrotropin-releasing hormone, thyroxine and thyroid-stimulating hormone were significantly downregulated. After challenge, the infected male mice and healthy female mice were caged together: the subsequent fetal death rate was increased, and the conception rate, litter size, number of live births and the birth weight were significantly reduced. Conclusions Infection of male BALB/c mice with the bovine isolate of N. caninum induced varying degrees of injury to the testis, epididymis and sperm of the mice, destroyed spermatogenesis and affected the reproductive capacity.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice

“…Sdc3 (upregulated 12-fold) is considered a regulator of obesity and has been proposed as a modulator of gonadal steroid function [ 62 ]. And finally, altered levels of Mrto4 in Balb/C mice (upregulated 3 fold in our DKO) have been linked to disruptions in spermatogenesis, fertility and testosterone levels in mice [ 63 ]. These findings further support our hypothesis that PADs play an important role in regulating gene expression in the testis, and more specifically, in regulating AR-mediated gene expression.…”

Infection of Trichinella spiralis Affects the Reproductive Capacity of ICR/CD-1 Male Mice by Reducing the Urine Pheromone Contents and Sperm Quality

“…Pathogen infection can reduce the attractiveness of urine from infected male mice [ 37 ] and the unhealthy state can even stimulate aversion from females in mate choice [ 38 ]. In addition to Trichinella spiralis , studies had reported that the infection of Dipetalonema evansi , Toxoplasma gondii , Trypanosoma vivax, and Neospora caninum could affect the reproductive capacity of male rodents [ 1 , 2 , 3 , 4 , 5 ]. Consistent with the previous research results [ 39 ], the odor attraction of urine of male mice was significantly reduced after Trichinella spiralis infection, which was shown in female mice escaping from the urine of male mice after parasitic infection.…”

“…Here, we found that the total number of offspring produced by male mice infected with Trichinella spiralis was 31% lower than that in the healthy male mice. Trichinella spiralis infection downregulated the gene expression levels of Herc4 [ 5 , 31 ], Mrto4 [ 30 ], and Ipo11 [ 48 ], genes closely related to the production and functional expression of sperm, which led to the decrease in sperm count. We also checked the sperm quality and found that sperm quality and sperm motility were significantly downregulated and sperm deformities were strongly upregulated in the experimental group.…”

“…The relationship between parasitic infection and reproductive injury had been reported [ 1 , 2 , 3 , 4 , 5 ], and most studies focused on the decreased sperm quality caused by parasitic infection. On the other hand, the mate choice of female mice could also be influenced by the parasitic infection of male mice, and females preferentially chose the parasite-free or parasite-resistant males [ 6 ].…”

Delayed puberty, gonadotropin abnormalities and subfertility in malePadi2/Padi4double knockout mice

“…Sdc3 (upregulated 12fold) is considered a regulator of obesity and has been proposed as a modulator of gonadal steroid function (62). And finally, altered levels of Mrto4 in Balb/C mice (upregulated 3 fold in our DKO) have been linked to disruptions in spermatogenesis, fertility and testosterone levels in mice (63). These findings further support our hypothesis that PADs play an important role in regulating gene expression in the testis, and more specifically, in regulating AR-mediated gene expression.…”