17beta-Estradiol and environmental estrogens significantly affect mammalian sperm function.

BACKGROUND: Compounds with estrogenic activity can affect reproductive function in mammals. This study investigated possible effects of 17beta-estradiol (E(2)) and three weakly estrogenic environmental estrogens on mammalian sperm capacitation and fertilizing ability in vitro. METHODS: Uncapacitated and capacitated mouse sperm suspensions were incubated for 30 min in the presence of E(2), genistein (Gen), 8-prenylnaringenin (8-PN) and nonylphenol (NP), and then assessed using chlortetracycline (CTC) fluorescence analysis. In addition, treated uncapacitated sperm suspensions were tested for changes in fertilizing ability. RESULTS: In uncapacitated cells, E(2) at >or=1 micromol/l and Gen, 8-PN and NP at >or=0.001 micromol/l, significantly stimulated capacitation and acrosome reactions. Hydroxytamoxifen (an estrogen antagonist) did not inhibit responses to any of these compounds. In capacitated cells, E(2) had no effect, but the other three compounds significantly stimulated acrosome reactions. Added to uncapacitated suspensions, 10 micromol/l E(2), 0.1 micromol/l Gen and 0.1 micromol/l 8-PN all significantly stimulated sperm fertilizing ability ( approximately 76% oocytes fertilized) compared with untreated control sperm ( approximately 36%). CONCLUSIONS: This study provides the first evidence that E(2) and environmental estrogens can significantly stimulate mammalian sperm capacitation, acrosome reactions and fertilizing ability, with the environmental estrogens being much more potent than E(2). The inability of hydroxytamoxifen to block these responses suggests that classical estrogen receptors may not be involved. Whether these responses have effects on fertility in vivo remains to be determined, along with the mechanisms of action involved.

Interaction of gametes with exogenous genes: possible opportunities for incorporation into embryonic genome.

The mechanism of incorporation of foreign DNA into newly fertilized eggs is poorly understood. It is not known with certainty if S phase DNA replication is required or if integration could occur at other times of the cell cycle that involve DNA strand breaks, such as chromatin rearrangements. We have investigated DNA strand breaks in mouse eggs and zygotes with a sensitive terminal uridine nucleotide end labeling (TUNEL) assay. Greater than 90% of all polar bodies and metaphase II chromosomes in freshly ovulated mouse eggs are TUNEL-assay positive. Approximately one-third of zygotes assayed 6 hr after fertilization contain at least one TUNEL assay positive pro-nucleus and/or decondensing sperm head. These results indicate that early embryonic DNA contains multiple transient DNA breaks that could play a role in the incorporation of foreign DNA.