Serum Hormone Characterization and Exogeneous Hormone Rescue of Bromodichloromethane-Induced Pregnancy Loss in the F344 Rat

Abstract

Previously, we demonstrated that bromodichloromethane (BDCM), a drinking water disinfection by-product, causes pregnancy loss in F344 rats when given on gestational days (GD) 6-10, encompassing the luteinizing hormone (LH)-dependent period of pregnancy (GD 7-10). Pregnancy loss, i.e., full-litter resorption, was associated with reduced serum progesterone levels; however, we were unable to identify an effect on serum LH. Here, we reevaluated serum LH levels using the more sensitive technique, DELFIA(R). We further sought to better define the temporal pattern of endocrine disruption caused by BDCM during pregnancy with more frequent sampling. Lastly, we attempted to prevent BDCM-induced pregnancy loss using exogenous progesterone or human chorionic gonadotropin (hCG), an LH-agonist. BDCM, in 10% Alkamuls(R), was dosed at 75 mg/kg/day by gavage to F344 rats on GD 6-10 (plug day = GD 0). BDCM-induced pregnancy loss was associated with marked reductions in serum progesterone and LH on GD 10. The decrease in serum LH consistently preceded the decrease in progesterone. In the hormone replacement studies, BDCM and progesterone were administered on GD 6-10, hCG on GD 8-10. BDCM was delivered at 100 mg/kg/day, progesterone at 10 mg/kg twice daily, and hCG at 0.5 IU/0.2 ml/rat. Both progesterone and hCG prevented BDCM-induced pregnancy loss. Thus, BDCM-induced pregnancy loss was associated with marked GD-10 reductions in serum LH and corresponding decreases in progesterone. Furthermore, coadministration of an LH agonist prevented pregnancy loss, supporting the hypothesis that BDCM-induced pregnancy loss in the rat occurs via an LH-mediated mode of action.

Maternal exposure to water disinfection by-products during gestation and risk of hypospadias

“…These substances can disrupt the activation of hormone dependent pathways required for male genital development and induce abnormalities of the penis 38. Bielmeier et al 39 40 demonstrated that exposure to bromodichloromethane (BDCM), a species of THM, causes pregnancy loss in rats. This BDCM-induced pregnancy loss was associated with reductions in luteinising hormone and a corresponding decrease in progesterone.…”

Are mothers less likely to breastfeed in harsh environments? Physical environmental quality and breastfeeding in the Born in Bradford study

“…The rate of elimination depends on the amount of fat a person has (World Health Organisation, ) and, as South Asian populations have more fat mass than Europeans (Deurenberg, Deurenberg‐Yap, & Guiricci, ; Stanfield, Wells, Fewtrell, Frost, & Leon, ), the Pakistani‐origin mothers in our sample may have retained DBPs in their bodies for longer, resulting in greater physiological impact. The compounds may impact breast development and lactation (Bielmeier, Best, & Narotsky, ; Rosen‐Carole et al, ) and may transfer from mother to infant (Batterman, Zhang, Wang, & Franzblau, ), potentially altering the taste and acceptability of breastmilk (Office of Environmental Health Hazard Assessment California Environmental Protection Agency, ). Alternatively, rather than being driven by physiological variation, the observed ethnic differences could be explained by social factors not controlled for, for example, diet and stress (Smith et al, ), or even fertility (although further data exploration shows this to be unlikely [results available on request]).…”

Changes of trihalomethanes (THMs) concentration in water distribution system

“…Chloroform (CHCl 3 ), bromoform (CHBr 3 ), bromodichloromethane (CHCl 2 Br), and dibromochloromethane (CHClBr 2 ) are the four compounds belonging to the group of THMs [1][2][3][4]. The presence of THMs in chlorinated drinking water and their lifetime exposure on humans have raised a great concern due to its carcinogenicity and recognition as potential risk to human health [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Several epidemiologic studies have suggested a linkage between THMs exposure and risk of bladder, colon, and rectum cancers [5,13].…”

“…Several epidemiologic studies have suggested a linkage between THMs exposure and risk of bladder, colon, and rectum cancers [5,13]. Exposure to THMs is also found to be associated with adverse reproductive outcomes [12,13]. The non-cancer effects of THMs are jaundice, *Corresponding author.…”