173
41. Swan SH, Elkin EP, Fenster L (2000) The question of declining sperm density revisited: an
analysis of 101 studies published 1934–1996. Environ Health Perspect 108(10):961–966
42. Merzenich H, Zeeb H, Blettner M (2010) Decreasing sperm quality: a global problem? BMC
Public Health 10:24
43. Sharpe RM (2012) Sperm counts and fertility in men: a rocky road ahead. Science & Society
Series on Sex and Science. EMBO Rep 13(5): 398–403.+ Toppari J, Larsen JC, Christiansen
P, Giwercman A, Grandjean P, Guillette LJ, Jr., Jegou B, Jensen TK, Jouannet P, Keiding N,
Leffers H, McLachlan JA, Meyer O, Muller J, Rajpert-De Meyts E, Scheike T, Sharpe R,
Sumpter J, Skakkebaek NE (1996) Male reproductive health and environmental xenoestrogens. Environ Health Perspect 104 (Suppl 4): 741–803
44. Rolland M, Le Moal J, Wagner V, Royere D, De Mouzon J (2013) Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and
2005 in France. Hum Reprod 28(2):462–470
45. Holmes L Jr, Escalante C, Garrison O, Foldi BX, Ogungbade GO, Essien EJ, Ward D (2008)
Testicular cancer incidence trends in the USA (1975-2004): plateau or shifting racial paradigm? Public Health 122(9):862–872
46. Toppari J, Kaleva M, Virtanen HE (2001) Trends in the incidence of cryptorchidism and
hypospadias, and methodological limitations of registry-based data. Hum Reprod Update
7(3):282–286
47. Paulozzi LJ, Erickson JD, Jackson RJ (1997) Hypospadias trends in two US surveillance systems. Pediatrics 100(5):831–834
48. Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001) Testicular dysgenesis syndrome:
an increasingly common developmental disorder with environmental aspects. Hum Reprod
16(5):972–978
49. Sharpe RM, Skakkebaek NE (2008) Testicular dysgenesis syndrome: mechanistic insights and
potential new downstream effects. Fertil Steril 89(2 Suppl):e33–e38
50. Nordkap L, Joensen UN, Blomberg Jensen M, Jorgensen N (2012) Regional differences and
temporal trends in male reproductive health disorders: semen quality may be a sensitive marker
of environmental exposures. Mol Cell Endocrinol 355(2):221–230
51. De Grava Kempinas W, Klinefelter GR (2014) Interpreting histopathology in the epididymis.
Spermatogenesis 4(2):e979114
52. Pineau C, Dupaix A, Jegou B (1999) The co-culture of Sertoli cells and germ cells: applications in toxicology. Toxicol In Vitro 13(4-5):513–520
53. Weiss M, Vigier M, Hue D, Perrard-Sapori MH, Marret C, Avallet O, Durand P (1997) Preand postmeiotic expression of male germ cell-specific genes throughout 2-week cocultures of
rat germinal and Sertoli cells. Biol Reprod 57(1):68–76
54. Klinefelter GR, Laskey JW, Roberts NL (1991) In vitro/in vivo effects of ethane dimethanesulfonate on Leydig cells of adult rats. Toxicol Appl Pharmacol 107(3):460–471
55. Klinefelter GR (1992) J Tissue Cult Methods 14:195–200
56. Chen YC, Bunick D, Bahr JM, Klinefelter GR, Hess RA (1998) Isolation and culture of epithelial cells from rat ductuli efferentes and initial segment epididymidis. Tissue Cell 30(1):1–13
57. Dufresne J, St-Pierre N, Viger RS, Hermo L, Cyr DG (2005) Characterization of a novel rat
epididymal cell line to study epididymal function. Endocrinology 146(11):4710–4720
58. Slott VL, Jeffay SC, Dyer CJ, Barbee RR, Perreault SD (1997) Sperm motion predicts fertility
in male hamsters treated with alpha-chlorohydrin. J Androl 18(6):708–716
59. Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell
JC, Kavlock RJ, Lambert PF, Hecht SS, Bucher JR, Stewart BW, Baan RA, Cogliano VJ, Straif
K (2016) Key characteristics of carcinogens as a basis for organizing data on mechanisms of
carcinogenesis. Environ Health Perspect 124(6):713–721
60. Arzuaga X, Smith MT, Gibbons CF, Skakkebaek NE, Yost EE, Beverly BEJ, Hotchkiss AK,
Hauser R, Pagani RL, Schrader SM, Zeise L, Prins GS (2019) Proposed key characteristics
of male reproductive toxicants as an approach for organizing and evaluating mechanistic evidence in human health Hazard assessments. Environ Health Perspect 127(6):65001
10 An Overview of Male Reproductive Toxicants: Facts and Opinions
41. Swan SH, Elkin EP, Fenster L (2000) The question of declining sperm density revisited: an
analysis of 101 studies published 1934–1996. Environ Health Perspect 108(10):961–966
42. Merzenich H, Zeeb H, Blettner M (2010) Decreasing sperm quality: a global problem? BMC
Public Health 10:24
43. Sharpe RM (2012) Sperm counts and fertility in men: a rocky road ahead. Science & Society
Series on Sex and Science. EMBO Rep 13(5): 398–403.+ Toppari J, Larsen JC, Christiansen
P, Giwercman A, Grandjean P, Guillette LJ, Jr., Jegou B, Jensen TK, Jouannet P, Keiding N,
Leffers H, McLachlan JA, Meyer O, Muller J, Rajpert-De Meyts E, Scheike T, Sharpe R,
Sumpter J, Skakkebaek NE (1996) Male reproductive health and environmental xenoestrogens. Environ Health Perspect 104 (Suppl 4): 741–803
44. Rolland M, Le Moal J, Wagner V, Royere D, De Mouzon J (2013) Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and
2005 in France. Hum Reprod 28(2):462–470
45. Holmes L Jr, Escalante C, Garrison O, Foldi BX, Ogungbade GO, Essien EJ, Ward D (2008)
Testicular cancer incidence trends in the USA (1975-2004): plateau or shifting racial paradigm? Public Health 122(9):862–872
46. Toppari J, Kaleva M, Virtanen HE (2001) Trends in the incidence of cryptorchidism and
hypospadias, and methodological limitations of registry-based data. Hum Reprod Update
7(3):282–286
47. Paulozzi LJ, Erickson JD, Jackson RJ (1997) Hypospadias trends in two US surveillance systems. Pediatrics 100(5):831–834
48. Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001) Testicular dysgenesis syndrome:
an increasingly common developmental disorder with environmental aspects. Hum Reprod
16(5):972–978
49. Sharpe RM, Skakkebaek NE (2008) Testicular dysgenesis syndrome: mechanistic insights and
potential new downstream effects. Fertil Steril 89(2 Suppl):e33–e38
50. Nordkap L, Joensen UN, Blomberg Jensen M, Jorgensen N (2012) Regional differences and
temporal trends in male reproductive health disorders: semen quality may be a sensitive marker
of environmental exposures. Mol Cell Endocrinol 355(2):221–230
51. De Grava Kempinas W, Klinefelter GR (2014) Interpreting histopathology in the epididymis.
Spermatogenesis 4(2):e979114
52. Pineau C, Dupaix A, Jegou B (1999) The co-culture of Sertoli cells and germ cells: applications in toxicology. Toxicol In Vitro 13(4-5):513–520
53. Weiss M, Vigier M, Hue D, Perrard-Sapori MH, Marret C, Avallet O, Durand P (1997) Preand postmeiotic expression of male germ cell-specific genes throughout 2-week cocultures of
rat germinal and Sertoli cells. Biol Reprod 57(1):68–76
54. Klinefelter GR, Laskey JW, Roberts NL (1991) In vitro/in vivo effects of ethane dimethanesulfonate on Leydig cells of adult rats. Toxicol Appl Pharmacol 107(3):460–471
55. Klinefelter GR (1992) J Tissue Cult Methods 14:195–200
56. Chen YC, Bunick D, Bahr JM, Klinefelter GR, Hess RA (1998) Isolation and culture of epithelial cells from rat ductuli efferentes and initial segment epididymidis. Tissue Cell 30(1):1–13
57. Dufresne J, St-Pierre N, Viger RS, Hermo L, Cyr DG (2005) Characterization of a novel rat
epididymal cell line to study epididymal function. Endocrinology 146(11):4710–4720
58. Slott VL, Jeffay SC, Dyer CJ, Barbee RR, Perreault SD (1997) Sperm motion predicts fertility
in male hamsters treated with alpha-chlorohydrin. J Androl 18(6):708–716
59. Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell
JC, Kavlock RJ, Lambert PF, Hecht SS, Bucher JR, Stewart BW, Baan RA, Cogliano VJ, Straif
K (2016) Key characteristics of carcinogens as a basis for organizing data on mechanisms of
carcinogenesis. Environ Health Perspect 124(6):713–721
60. Arzuaga X, Smith MT, Gibbons CF, Skakkebaek NE, Yost EE, Beverly BEJ, Hotchkiss AK,
Hauser R, Pagani RL, Schrader SM, Zeise L, Prins GS (2019) Proposed key characteristics
of male reproductive toxicants as an approach for organizing and evaluating mechanistic evidence in human health Hazard assessments. Environ Health Perspect 127(6):65001
10 An Overview of Male Reproductive Toxicants: Facts and Opinions