Frequent and mild scrotal heat stress impairs embryo development, implantation and offspring sex ratio in mice

Research question Frequent and mild scrotal heat stress (fmSHS) often occurs in humans. The aim of this study was to determine the impact of fmSHS on natural fertility, the IVF–embryo transfer (IVF–ET) process and the offspring sex ratio. Design Male mice were randomly divided into four groups: no scrotal heat stress (SHS) (controls) and those subjected to SHS at 37°C, 39°C or 41°C for 30 min once a week for 5 consecutive weeks. The testis, epididymis and sperm quality were assessed to evaluate the effects of different degrees of SHS, to establish an fmSHS model. Then, natural fertility, IVF–embryo transfer (IVF–ET) results, embryo development, offspring sex ratio and the X/Y chromosome-bearing sperm ratio were examined. Results SHS at 39°C and 41°C caused mild impairment to spermatozoa, leading to a phenotype similar to oligoasthenozoospermia in humans. Given that most SHS conditions in humans are close to body temperature, SHS of 39°C was adopted to build the fmSHS model. fmSHS reduced the fertilization rate, impaired on-time development and reduced the implantation rate of the embryos in the IVF–ET process, but it did not affect the development or function of blastocysts. The fmSHS mice produced more Y chromosome-bearing spermatozoa and propagated more male offspring. Conclusions fmSHS not only reduced the fertilization ability of spermatozoa but also influenced their function beyond fertilization, in addition to changing the offspring sex ratio. These results may help to shed new light on the infertility treatment of males with scrotal heat risk and the health concerns of offspring propagated from these fathers.