Low Level of Cystic Fibrosis Transmembrane Conductance Regulator Is Associated with Human Sperm Autophagy and Vitality

Low sperm motility is one of the main causes of male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR, an anion channel protein) is related to the progressive motility of sperm. CFTR disruptor CFTRinh-172 or forskolin (FSK) in this study were used to treat human sperm separately, and the rates of sperm autophagy and progressive motility, mitochondrial membrane potential (MMP) and ATP concentration, and the expression levels of related factors were detected to explore their relationship. It was showed that sperms treated with CFTRinh-172 or FSK reduced the levels of cAMP, CFTR and PKA, but increased sperm autophagy rate, expression levels of AMPK and LC3B. However, reactive oxygen species content had no significant difference. It was indicated that low level of CFTR performed with cAMP and its downstream effectors such as PKA and AMPK to regulate mitochondrial structure and function, leading to increased autophagy rate and reduced vitality of sperm.

Novel insights into necrozoospermia from a single-center study:reference ranges,possible etiology,and impact on male fertility

Necrozoospermia is a poorly documented condition with a low incidence,and its definition and clinical significance are unclear.Herein,we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive outcomes.We extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm vitality.Necrozoospermia was present in 3.4%(22/650)of our study population,and the lower cut-off value for sperm vitality was 75.3%.We compared two methods for assessing sperm vitality(eosin-nigrosin head staining and hypo-osmotic swelling test[HOST]),for which the percentage in the eosin-nigrosin group(mean±standard deviation[s.d.]:77.5%±10.5%)was significantly higher than that in the HOST group(mean±s.d.:58.1%±6.7%[5-10 min after incubation]and 55.6%±8.2%[25-30 min after incubation];both P<0.001).The incidence of necrozoospermia increased with age(odds ratio[OR]=1.116,95%confidence interval[CI]:1.048-1.189,P=0.001),while the percentage of normal sperm morphology and DNA fragmentation index(DFI)were significantly associated with necrozoospermia,with ORs of 0.691(95%CI:0.511-0.935,P=0.017)and 1.281(95%CI:1.180-1.390,P<0.001),respectively.In the following 6 months,we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection(ICSI)and pregnancy outcomes between the two groups.The necrozoospermia group had a significantly lower normal fertilization rate(74.7%vs 78.2%,P=0.041;OR=0.822;95%CI:0.682-0.992)than that in the nonnecrozoospermia group.This study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.