Reduced Prostaglandin Levels in the Semen of Men with Very High Sperm Concentrations R
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Reduced prostaglandin levels in the semen of men with very high sperm concentrations R. W. Kelly, I. Cooper and A. A. Templeton Medical Research Council, Unit ofReproductive Biology, 2 Forrest Road, Edinburgh EHI 2QW, and *Department of Obstetrics and Gynaecology, University of Edinburgh, 23 Chalmers Street, Edinburgh EH3 9ER, U.K. Summary. The prostaglandin levels have been measured in a group of men with sperm concentrations greater than 300 \m=x\106/ml and compared with the levels in men with sperm concentrations of 50 to 150 \m=x\106/ml. The distribution of the PG levels in all groups was highly skewed but the data could be transformed to a normal distribution by taking logarithms. Comparison of the PG levels showed a highly significant lowering of the PG levels in the polyzoospermic group when compared with either of the groups with normal sperm concentrations. Introduction Although prostaglandins (PGs) were first discovered in human seminal plasma (Goldblatt, 1933; von Euler, 1934, 1935) and although a relationship between PG levels in semen and fertility were apparently established in early investigations of seminal PG content (Bygdeman, Fredricsson, Svanborg & Samuelsson, 1970), the function of these compounds in semen is still not clear. The first PGs to be found in human semen were those of the E and F series (Samuelsson, 1963) which were followed by reports of the A, B, 19-hydroxy A and 19-hydroxy series (Hamberg & Samuelsson, 1966).The finding that the 19-hydroxy PGEs are the major PGs of human semen (Taylor & Kelly, 1974; Jonsson, Middleditch & Desiderio, 1975) has led to the suggestion that the A, B, 19-hydroxy A and 19-hydroxy PGs in semen and elsewhere are artefacts (Middleditch, 1975). The average ejaculate of a fertile man will contain around 1 mg PG which consists mainly of the 4 E type PGs; PGE-1, PGE-2, 19-OH PGE-1 and 19-OH PGE-2 (Templeton, Cooper & Kelly, 1978). Early measurements of seminal PGs showed that there was no apparent correlation between the PG content of the semen and any common measure of semen quality (Hawkins, 1968; Bygdeman et al, 1970; Brummer & Gillespie, 1972) although several studies have reported an apparently significant difference in the PG content of semen from couples with otherwise unexplained infertility when compared to levels in fertile men (Bygdemann et al, 1970; Ito & Katayama, 1971; Brummer & Gillespie, 1972; Collier, Flower & Stanton, 1975). All these comparisons have been complicated, and sometimes perhaps invalidated, by the skewed distribution of most seminal variables, including PG content (Hawkins, 1968) and the wide range of PG levels in normal fertile men (Templeton et al, 1978). Now that the qualitative nature of the seminal PGs is more clearly understood, we have re- examined the possibility of a connection between sperm count and seminal PG levels. In this study we have measured the PG content of the semen from a group of men with sperm counts greater than 300 106/ml who are all polyzoospermic (Eliasson, 1975) and compared this with the PG content of semen samples in which the count was in the range of 50-150 lOVml. Downloaded from Bioscientifica.com at 10/04/2021 06:21:44PM via free access Materials and Methods Single semen samples were obtained from fertile men between 20 and 40 years of age (Templeton et al, 1978) and from men attending an infertility clinic. All samples were obtained by masturbation between 07:00 and 10:00 h. Routine measurements of sperm count, motility and seminal volume were carried out on samples as soon as they were received, which was usually within 3 h of ejaculation. All semen samples had motilities greater than 35%. Aliquots of the semen samples were placed into methoxyamine hydrochloride solution within 6 h of ejaculation and were then stored at 4°C until analysed for PG levels using a gas chromatography method (Cooper & Kelly, 1975). The precision of this method was 6% (s.d.) for PGE measurements and 12% (s.d.) for 19-OH PGE measurements. The variation of PG levels from day to day for one person has been estimated at 23% for PGEs and 25% for 19-OH PGEs (Templeton et al, 1978). The sensitivity of the method was 0-2 pg PG/ml semen. Semen samples were categorized according to their sperm count. Group A consisted of 32 men attending an infertility clinic who had sperm counts in the range 50-150 106/ml. Group included 15 men who had fathered children within the last year with sperm counts in the same range. Group C comprised 9 men from the infertility clinic and one man who had fathered a child within the last year with sperm counts greater than 300 x 106/ml. Data were analysed for significance using the Wilcoxon Rank Sum test (Wilcoxon, 1945) or were transformed by taking logarithms and then analysed by Student's t test. Results The widest range of PG levels (Table 1) was found in Group B. The total PGE + 19-OH PGE content of the ejaculate in this group ranged from 191 to 3717 pg with a mean content of 1049 pg. The PG levels and seminal volumes in Group A did not differ significantly from those of Group but Group A was without the few very high levels of PG found in Group B. The total PGE + 19-OH PGE content of Group A ranged from 211 to 3783 pg with a mean of 1077 pg. The range of sperm concentrations in Group C was from 300 to 614 106/ml and the range of total sperm content of the ejaculates was from 213 to 2750 IO6. The total PGE + 19-OH PGE content of the ejaculates in Group C was from 71 to 2285 pg with a mean of 464 pg. The concentrations of 19-OH PGE and of PGE + 19-OH PGE in Group C were highly significantly different from those of Group A and (Table 1). The differences in PGE levels were less marked with a significant difference clearly demonstrated between Groups C and A only. When the PG content of the ejaculates was examined the total E + 19-OH PGE content in - ta) - -I (b) Groups A + Groups A + 5- H -P- - - - _D_ io¬ 10- C C Group 5 Group -R-r^-r— 500 1000 1500 1000 2000 3000 4000 Concentration (^ug/ml) Content fag) Text-fig. 1. The distribution of (a) concentration and (b) content of PGE + 19-OH PGE in ejaculates from Groups A + and Group C. Downloaded from Bioscientifica.com at 10/04/2021 06:21:44PM via free access Table 1. Prostaglandin concentrations in a group of polyzoospermic men (Group C, >300 x lOVml) and two groups of men with normal sperm counts (Groups A and B, 50-150 lOVml) Group (sperm count) Difference between groups* A (N = 32) ( =15) ( = 10) C from A C from B A from PGE (Mg/ml) Mean 55 89 20 (range) (5-139) (2-262) (5-63) < 001 N.S.t N.S.t Median 48 71 13 log10of Mean 1-60 1-67 1-17 < 0005 < 0-05 data Median 1-67 1-85 1-11 19-OH PGE fag/ml) Mean 247 302 101 (range) (460-670) (64-1094) (31-310) < 0-01 P<001 N.S.t Median , 207 209 68 log10of Mean 2-30 2-27 1-9 < 0-001 < 0025 data Median 2-31 2-32 1-83 PGE + 19-OH PGE (jig/ml) Mean 302 392 121 (range) (72-783) (91-1239) (45-341) < 001 < 001 N.S.t Median 257 303 80 log10of I Mean 2-41 2-48 1-90 < 0-001 <0001 data I Median 2-39 2-48 1-90 Volume (ml) Mean 3-7 2-95 307 (range) (1-6-7-8) (1-3-4-6) (0-6-6-7) N.S.t N.S.t Median 3-7 3-05 2-45 * Student's t test was used on log10 data and the Wilcoxon Rank Sum test was used on untransformed data. t Not significant at the 0-1 level using Student's t test (see text). t Not significant at the 0-1 level using Wilcoxon Rank Sum test. Groups A and B, combined together as shown in Text-fig. 1 and independently, differed significantly (P < 0-01 using the Wilcoxon Rank Sum test) from the PG content in Group C. The distributions of PG concentrations and content were all skewed (see Text-fig. 1). No significant differences in motility were observed between the three groups. Discussion Previous studies of the PG content of semen have not revealed a correlation of PG levels with other commonly measured parameters such as sperm count, motility, longevity of the spermatozoa or seminal volume (Asplund, 1947; Hawkins, 1968; Bygdeman et al, 1970; Brummer & Gillespie, 1972; Collier et al, 1975) although several reports have noted an apparently significant increase in seminal PG levels in a group of azoospermic men when compared with a group of oligozoospermic men (Sturde, 1968; Perry & Desiderio, 1977). The difference between these groups, however, took account neither of the aetiology of the azoospermia nor of the skewed distribution of the seminal PG levels which has previously been described (Hawkins, 1968) and is confirmed in this study. The results given here show a highly significant difference of seminal PG levels in men with sperm counts greater than 300x 106/ml and in two populations of men with counts of 50-150 106/ml. All three groups exhibited a highly skewed distribution of PG levels as is evident from Downloaded from Bioscientifica.com at 10/04/2021 06:21:44PM via free access the difference between the mean and the median levels (Table 1) and is shown for Groups A + and Group C in Text-fig.