Gestational Exposure to Bisphenol-A Affects the Function and Proteome Profile of F1 Spermatozoa in Adult Mice.
Environ Health Perspect. 2016 Jul 6. Epub 2016 Jul 6. PMID: 27384531
Md Saidur Rahman
BACKGROUND: Maternal exposure to the endocrine disruptor bisphenol-A (BPA) has been linked to offspring reproductive abnormalities. Exactly how BPA affects offspring fertility, however, remains poorly understood.
OBJECTIVES: The aim of the present study was to evaluate the effect of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice.
METHODS: Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50μg, 5 mg, and 50 mg•kg bw(-1)•day(-1)), on embryonic days 7 to 14. We investigated function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa as a manner to monitor their functional affiliation to diseases.
RESULTS: We found that BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelium in testis and decreased protein kinase-A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and pathogenesis of several diseases.
CONCLUSIONS: Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa.