Successful lowering of epididymal carnitine by administration of pivalate to rats

Abstract

SummaryThis study was designed to lower the epididymal content of carnitine in male rats and to examine subsequent effects on fertility and sperm motility. As carnitine is transported from serum into the epididymal lumen a method to lower serum carnitine was sought. Administration of 20 mmol/L sodium pivalate in the drinking water for up to 5 weeks substantially lowered serum carnitine (to 20% of control levels within 1 week) and reduced epididymal carnitine content (to 25% of control levels in the proximal and 52% of control in distal regions) within 2 weeks. Carnitine in distal cauda epididymal¯uid was also reduced (to 30% of control levels) but no changes were observed in the sperm carnitine content. The percentage motility and kinematic parameters of spermatozoa released from four epididymal regions and diluted into arti®cial medium were unaltered by the treatment, and all males retained their fertility in mating tests performed at weekly intervals. Increasing the dose of sodium pivalate administered to 60 mmol/L for 2 weeks lowered serum carnitine concentration more but did not further decrease epididymal carnitine content and altered neither sperm motility nor male fertility. The rat epididymis secretes an excessive amount of carnitine into its lumen so that substantially lowering the tissue content does not reduce sperm carnitine or affect their motility or fertilizing ability.

Effects of Putative Epididymal Osmolytes on Sperm Volume Regulation of Fertile and Infertile c‐ros Transgenic Mice

“…Insofar as this animal model can be useful for investigating the relationship between epithelial and sperm function, for purposes of developing a contraceptive for males, these observations suggest that attacking the sperm channels to limit the uptake of epididymal osmolytes might be more effective than targeting the epithelial transporters in order to limit the provision of luminal secretions to the sperm. This reiterates findings in rats and hamsters that reducing epididymal carnitine by increasing excretion of pivalolyl carnitine does not lead to infertility or reduce sperm motility because sperm carnitine was unaltered (Cooper et al, 1997; Lewin et al, 1997).…”

Dysfunctions of the epididymis as a result of primary carnitine deficiency in juvenile visceral steatosis mice

“…Therefore, seminal carnitine levels are regarded as an index of androgenization and is also used for determination of the site of obstruction in azoospermia patients [12, 13]. Despite such values, however, no animal models for investigating the dysfunctions of the epididymis due to carnitine deficiency are available, except for several chemical studies which have examined the reduction of carnitine with pivalic acid [5, 14].…”