Taurine and its transporter TAUT positively affect male reproduction and early embryo development.

study questionAre taurine and its transporter TAUT associated with spermiogenesis and early embryo development? SUMMARY ANSWER: Morphologically abnormal spermatozoa increased after local functional interference by intratesticular injection, and taurine depletion significantly reduced the normal embryo numbers in vivo and blastocyst formation rate in vitro. WHAT IS KNOWN ALREADY: Taurine is one of the most abundant amino acids in the male reproductive system and it has been demonstrated that taurine can efficiently improve spermatogenic function in rat models of testicular injury. However, limited information is known about the role of taurine and its transporter TAUT in spermatogenesis and early embryo development. STUDY DESIGN, SIZE, DURATION: Clinical characteristics from 110 couples who have experienced recurrent pregnancy loss (RPL) were collected from December 2014 to March 2018. According to whether a fetal heartbeat was seen in the previous pregnancy under ultrasonic monitoring, patients with RPL were divided into two groups: an RPL without heartbeat (pregnancy with no fetal heartbeat, ROH) group, and an RPL with heartbeat (one or more pregnancies with fetal heartbeat, RWH) group. Semen samples (21 ROH and 20 RWH) were finally used for metabolomic analysis. Furthermore, semen samples were obtained from 30 patients with teratozoospermia (normal sperm morphology <4%) seeking evaluation for infertility and 25 age-matched control subjects with normal semen quality for western blotting. Animal experiments were performed in CD-1/ICR mice. PARTICIPANTS/MATERIALS, SETTING,

methodsMetabolomics was performed to determine the metabolic changes between the ROH and RWH groups. Sperm proteins from patients with teratozoospermia and healthy controls were extracted for detecting TAUT expression using western blot analysis. Immunofluorescence was used to characterize the localization of TAUT in the testis and ejaculated spermatozoa. Functional analysis in mice was performed by intratesticular injection of siRNAs or antagonist (β-alanine) and 5% β-alanine was provided in drinking water to 3-week-old male mice for 5 weeks with the aim of depleting taurine. Murine epididymal spermatozoa were stained with hematoxylin and eosin for morphological assessment. IVF and mating tests were performed in mice for assessing fertility. MAIN RESULTS AND THE ROLE OF CHANCE: Metabolomic analysis demonstrated that the taurine content was lower in spermatozoa but higher in seminal plasma from the ROH than the RWH group. TAUT expression was lower in spermatozoa from patients with teratozoospermia than controls. Immunofluorescence showed that TAUT was localized to the manchette in mouse elongated spermatids functional analysis showed that morphologically abnormal spermatozoa increased after interference, and this defect increased after supplementation with 5% β-alanine but was improved by 5% taurine supplementation. Supplementation with 5% β-alanine significantly reduced the normal embryo number in the mouse uterus as well as blastocyst formation rate in vitro. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The sample size was low and larger cohorts are needed to confirm the positive effect of taurine on human sperm quality. A comprehensive safety examination should be performed to evaluate whether taurine is a possible treatment for teratozoospermia. Furthermore, the specific molecular mechanism of TAUT involvement in spermiogenesis remains to be clarified. WIDER IMPLICATIONS OF THE

findingsThe study provides new insights into the role of taurine and its transporter TAUT in male reproduction and embryo development. The results also indicate that TAUT is a promising molecular candidate for the assessment of sperm quality, which may contribute to the diagnosis and treatment for teratozoospermia. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Natural Science Foundation of China (no. 81774075, 31900605, 81971451), Jiangsu Science and Technology Program Grant (BK20190654) and Maternal and child health scientific research of Jiangsu Province (F202121). The authors declare no competing financial interests.