Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity.
Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 μM, 2-8 days) decreased (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days±VCD (30 μM) caused an increase (P<0.05) in primordial, and a decrease (P<0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.
Mark-Kappeler
Connie J
CJ
Department of Physiology, University of Arizona, Tucson, AZ 85724-5051, USA.
Sen
Nivedita
N
Keating
Aileen F
AF
Sipes
I Glenn
IG
Hoyer
Patricia B
PB
D000818:Animals; D000831:Animals, Newborn; D054304:Anti-Mullerian Hormone / Q000032:analysis / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053138:Cyclohexenes / Q000633:toxicity*; D005260:Female; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution; D014753:Vinyl Compounds / Q000633:toxicity*
D053138:Cyclohexenes; D014753:Vinyl Compounds; C012606:4-vinyl-1-cyclohexene dioxide; D054304:Anti-Mullerian Hormone
Dev Biol. 2006 Nov 1;299(1):1-11
16970938
Endocrinology. 2001 Nov;142(11):4891-9
11606457
Toxicol Appl Pharmacol. 2002 Oct 15;184(2):107-15
12408955
Toxicol Appl Pharmacol. 1996 Aug;139(2):402-10
8806858
Mol Cell Endocrinol. 2005 Apr 29;234(1-2):81-6
15836956
Am Ind Hyg Assoc J. 1977 May;38(5):205-10
868759
Toxicol Appl Pharmacol. 1996 Aug;139(2):394-401
8806857
Biol Reprod. 2011 Apr;84(4):743-51
21076081
Trends Endocrinol Metab. 2008 Nov;19(9):340-7
18805020
J Endocrinol Invest. 2003;26(3 Suppl):23-8
12834017
Science. 2003 Jul 11;301(5630):215-8
12855809
Biol Reprod. 2010 Feb;82(2):246-56
19794155
Endocrinology. 2007 May;148(5):2301-8
17255205
Reproduction. 2002 Nov;124(5):601-9
12416998
Trends Endocrinol Metab. 2007 Mar;18(2):58-65
17275321
Endocrinology. 2002 Mar;143(3):1076-84
11861535
Endocrinology. 1995 Nov;136(11):4951-62
7588229
Endocrinology. 1999 Dec;140(12):5789-96
10579345
Reproduction. 2007 Aug;134(2):209-21
17660231
Endocr Rev. 2009 Aug;30(5):438-64
19589950
J Clin Endocrinol Metab. 2006 Oct;91(10):4064-9
16895952
Int Rev Cytol. 1991;124:43-101
2001918
Toxicol Appl Pharmacol. 2005 Mar 1;203(2):114-23
15710172
Reprod Toxicol. 1994 Nov-Dec;8(6):509-14
7881202
Biol Reprod. 2008 Aug;79(2):318-27
18448842
Reprod Toxicol. 2002 Nov-Dec;16(6):775-81
12401505
Toxicol Appl Pharmacol. 2009 Dec 1;241(2):127-34
19695275