Reproductive Toxicology, Vol. 7, pp. 477-481, 1993 0890-6238/93 $6.00 + .00 Printed in the U.S.A. All rights reserved. Copyright © 1993 Pergamon Press Ltd. • Brief Communication EXCESS CHOLINE AVAILABILITY: A TRANSIENT EFFECT ON SPERMATOGENESIS IN THE RAT K. D. VACHHRAJANI, A. P. SAHU, and K. K. DUTTA Industrial Toxicology Research Centre, Lucknow, India Abstract -- The reproductive effects of choline (trimethyl-~hydroxyethylammonium) are unknown. Excess dietary intake of choline may occur in humans. Adult male rats were administered i.p. aqueous choline chloride (25 mg/rat, daily for 12 or 24 days). Administration of excess choline for 12 days did not significantly alter spermatogenesis. Administration for 24 days depleted pachytene spermatocytes until posttreatment day 5, while slight proliferation of spermatogonia was noted from day 5 onwards. By day 12, the tubules showed almost normal cellular associations. It is suggested that perhaps a prolonged administration of excess choline may prove to be toxic to male reproduction. Key Words: choline; spermatogenesis; excess dietary intake. INTRODUCTION Choline (trimethyl-fl-hydroxyethylammonium) is found in many plant and animal tissues, chiefly as the major component of lecithin (phosphatidylcho- line) (1). Choline, as a vitamin, influences general metabolism and plays an important role in the main- tenance of lipid transport (2). Choline is an essential component of cell membranes (3) and also a constit- uent of the neurotransmitter acetylcholine (4). Administration of choline as a feed supplement in animals has been investigated (5). Choline supple- mentation increases transport of free fatty acids into cow milk but does not alter milk composition (6) nor does choline supplementation of lactating sows benefit piglets (7). In experimental animals, choline deficiency produces fatty infiltration, renal damage, and increased sensitivity to carcinogens (8,9), whereas choline sufficiency may induce neoplastic lesions (10). Choline is metabolized by gut bacteria to form mono-, di-, and trimethylamines, which could be substrates for production of nitrosamines that have marked carcinogenic effects (11). Choline is used for treatment of neurologic and Address correspondence to Dr. K. D. Vachhrajani at his present address: Department of Zoology, Faculty of Science, M. S. University of Baroda, Vadodara 390 002, India. Reeeioed 29 October 1992; Revision received 29 December 1992; Accepted 22 January 1993. psychiatric disorders (12). Choline administration also provides protection against various toxic com- pounds (13,14). Choline is an important precursor for the secretory products of the seminal vesicle and epididymis (15), and choline deficiency leads to infertility in experimental animals (16). Possible adverse effects of choline sufficiency on reproduc- tion have not been studied to date. Deficiency of choline has not been reported in humans, but a 6- to 8-fold variation is found in daily dietary consump- tion of choline (17). It is possible, then, that excess dietary choline intake occurs in humans. The lack of existing data prompted us to study the effect of excess choline availability on male re- production. The present investigation is a prelimi- nary report on effects of excess choline administra- tion on spermatogenesis in rats. MATERIALS AND METHODS Male rats (300 g body weight) were obtained from the animal house of the Industrial Toxicology Research Centre and acclimatized in plastic cages for 1 week in standard conditions of husbandry. Ani- mals were divided into three groups: Groups I and II rats (n = 25 each) were administered aqueous solution of choline chloride, 25 rag/rat i.p. daily for 12 and 24 days. This dose was 5% of the LDs0 value of choline chloride in adult rats (450 mg/kg i.p.) (18). In our earlier studies (19) three doses of choline 477