Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2013

Open Access 01-12-2013 | Research

Maternal nutrient restriction in the ewe from early to midgestation programs reduced steroidogenic enzyme expression and tended to reduce progesterone content of corpora lutea, as well as circulating progesterone in nonpregnant aged female offspring

Authors: Nathan M Long, Nuermaimaiti Tuersunjiang, Lindsey A George, Caleb O Lemley, Yan Ma, William J Murdoch, Peter W Nathanielsz, Stephen P Ford

Published in: Reproductive Biology and Endocrinology | Issue 1/2013

Login to get access

Abstract

Background

Previously we reported decreased circulating progesterone and fertility in one and two year old ewes born to undernourished mothers. This study was designed to investigate if this reduction in progesterone persisted into old age, and if it did, what mechanisms are involved.

Methods

Ewes were fed a nutrient restricted (NR, 50% of NRC recommendations) or control (C, 100% of NRC) diets from day 28 to 78 of gestation, then all were fed to requirements through parturition and weaning. Female offspring (4 per treatment group) were maintained as a group and fed to requirements from weaning until assigned to this study at 6 years of age. Ewes were synchronized for estrus (day 0) and blood samples were collected daily from day 0 to day 11 before necropsy on day 12. Blood serum and luteal tissue were assayed for progesterone concentrations by validated radioimmunoassay.

Results

Circulation progesterone concentrations tended to be lower (P = 0.06) in NR than C offspring from day 0 to 11 of the estrous cycle. While total luteal weight was similar across groups, total progesterone content also tended to be reduced (P = 0.07) in luteal tissue of NR than C offspring. Activity of hepatic progesterone catabolizing enzymes and selected angiogenic factors in luteal tissue were similar between groups. Messenger RNA expression of steroidogenic enzymes StAR and P450scc were reduced (P < 0.05), while protein expression of StAR tended to be reduced (P < 0.07) and P450scc was reduced (P < 0.05) in luteal tissue of NR versus C offspring.

Conclusions

There appears to be no difference in hepatic steroid catabolism that could have led to the decreased serum progesterone. However, these data are consistent with the programming of decreased steroidogenic enzyme expression in CL of NR offspring, leading to reduced synthesis and secretion of progesterone.
Appendix
Available only for authorised users
Literature
1.
Dixon AB, Knights M, Winkler JL, Marsh DJ, Pate JL, Wilson ME, Dailey RA, Seidel G, Inskeep EK: Patterns of late embryonic and fetal mortality and association with several factors in sheep. J Anim Sci. 2007, 85: 1274-1284. 10.2527/jas.2006-129.CrossRefPubMed
2.
Larson SF, Butler WR, Currie WB: Pregnancy rates in lactating dairy cattle following supplementation of progesterone after artificial insemination. Anim Reprod Sci. 2007, 102: 172-179. 10.1016/j.anireprosci.2007.02.023.CrossRefPubMed
3.
Bloomfield FH, Oliver MH, Giannoulias CD, Gluckman PD, Harding JE, Challis JR: Brief undernutrition in late-gestation sheep programs the hypothalamic-pituitary-adrenal axis in adult offspring. Endocrinology. 2003, 144: 2933-2940. 10.1210/en.2003-0189.CrossRefPubMed
4.
Rae MT, Kyle CE, Miller DW, Hammond AJ, Brooks AN, Rhind SM: The effects of undernutrition, in utero, on reproductive function in adult male and female sheep. Anim Reprod Sci. 2002, 72: 63-71. 10.1016/S0378-4320(02)00068-4.CrossRefPubMed
5.
Murdoch WJ, Van Kirk EA, Vonnahme KA, Ford SP: Ovarian responses to undernutrition in pregnant ewes. Reprod Biol Endocrinol. 2003, 1: 6-10.1186/1477-7827-1-6.PubMedCentralCrossRefPubMed
6.
Long NM, Nijland MJ, Nathanielsz PW, Ford SP: The effect of early to mid-gestational nutrient restriction on female offspring fertility and hypothalamic-pituitary-adrenal axis response to stress. J Anim Sci. 2010, 88: 2029-2037. 10.2527/jas.2009-2568.CrossRefPubMed
7.
Murray M: Microsomal cytochrome P450-dependent steroid metabolism in male sheep liver. Quantitative importance of 6 beta-hydroxylation and evidence for the involvement of a P450 from the IIIA subfamily in the pathway. J Steroid Biochem Mol Biol. 1991, 38: 611-619. 10.1016/0960-0760(91)90320-5.CrossRefPubMed
8.
Murray M: Participation of a cytochrome P450 enzyme from the 2C subfamily in progesterone 21-hydroxylation in sheep liver. J Steroid Biochem Mol Biol. 1992, 43: 591-593. 10.1016/0960-0760(92)90248-H.CrossRefPubMed
9.
MacLaughlin SM, Walker SK, Kleemann DO, Sibbons JP, Tosh DN, Gentili S, Coulter CL, McMillen IC: Impact of periconceptional undernutrition on adrenal growth and adrenal insulin-like growth factor and steroidogenic enzyme expression in the sheep fetus during early pregnancy. Endocrinology. 2007, 148: 1911-1920.CrossRefPubMed
10.
Khorram NM, Magee TR, Wang C, Desai M, Ross M, Khorram O: Maternal undernutrition programs offspring adrenal expression of steroidogenic enzymes. Reprod Sci. 2011, 18: 931-940. 10.1177/1933719111404613.PubMedCentralCrossRefPubMed
11.
Yamashita H, Murayama C, Takasugi R, Miyamoto A, Shimizu T: BMP-4 suppresses progesterone production by inhibiting histone H3 acetylation of StAR in bovine granulosa cells in vitro. Mol Cell Biochem. 2011, 348: 183-190. 10.1007/s11010-010-0653-9.CrossRefPubMed
12.
Berisha B, Meyer HH, Schams D: Effect of prostaglandin F2 alpha on local luteotropic and angiogenic factors during induced functional luteolysis in the bovine corpus luteum. Biol Reprod. 2010, 82: 940-947. 10.1095/biolreprod.109.076752.CrossRefPubMed
13.
Vonnahme KA, Redmer DA, Borowczyk E, Bilski JJ, Luther JS, Johnson ML, Reynolds LP, Grazul-Bilska AT: Vascular composition, apoptosis, and expression of angiogenic factors in the corpus luteum during prostaglandin F2alpha-induced regression in sheep. Reproduction. 2006, 131: 1115-1126. 10.1530/rep.1.01062.CrossRefPubMed
14.
15.
Behrman HR, Kodaman PH, Preston SL, Gao S: Oxidative stress and the ovary. J Soc Gynecol Investig. 2001, 8: S40-42. 10.1016/S1071-5576(00)00106-4.CrossRefPubMed
16.
Diemer T, Allen JA, Hales KH, Hales DB: Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology. 2003, 144: 2882-2891. 10.1210/en.2002-0090.CrossRefPubMed
17.
Cox AG, Winterbourn CC, Hampton MB: Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. Biochem J. 2010, 425: 313-325. 10.1042/BJ20091541.CrossRef
18.
National Research Council Committee on Animal Nutrition: Nutrient Requirements of Sheep. 1985, Washington, DC: National Academy Press
19.
McPherson LA, Van Kirk EA, Murdoch WJ: Localization of stress protein-70 in ovine corpora lutea during prostaglandin-induced luteolysis. Prostaglandins. 1993, 46: 433-440.CrossRefPubMed
20.
Nelson AC, Huang W, Moody DE: Variables in human liver microsome preparation: impact on the kinetics of l-alpha-acetylmethadol (LAAM) n-demethylation and dextromethorphan O-demethylation. Drug Metab Dispos. 2001, 29: 319-325.PubMed
21.
Savlík M, Polácková L, Szotáková B, Lamka J, Velík J, Skálová L: Activities of biotransformation enzymes in pheasant (Phasianus colchicus) and their modulation by in vivo administration of mebendazole and flubendazole. Res Vet Sci. 2007, 83: 20-26. 10.1016/j.rvsc.2006.10.013.CrossRefPubMed
22.
Palackal NT, Lee SH, Harvey RG, Blair IA, Penning TM: Activation of polycyclic aromatic hydrocarbon trans-dihydrodiol proximate carcinogens by human aldo-keto reductase (AKR1C) enzymes and their functional overexpression in human lung carcinoma (A549) cells. J Biol Chem. 2002, 277: 24799-24808. 10.1074/jbc.M112424200.CrossRefPubMed
23.
Lemley CO, Butler ST, Butler WR, Wilson ME: Short communication: insulin alters hepatic progesterone catabolic enzymes cytochrome P450 2C and 3A in dairy cows. J Dairy Sci. 2008, 91: 641-645. 10.3168/jds.2007-0636.CrossRefPubMed
24.
Ford SP, Zhang L, Zhu M, Miller MM, Smith DT, Hess BW, Moss GE, Nathanielsz PW, Nijland MJ: Maternal obesity accelerates fetal pancreatic beta-cell but not alpha-cell development in sheep: prenatal consequences. Am J Physiol Regul Integr Comp Physiol. 2009, 297: R835-843. 10.1152/ajpregu.00072.2009.PubMedCentralCrossRefPubMed
25.
Ma Y, Zhu MJ, Zhang L, Hein SM, Nathanielsz PW, Ford SP: Maternal obesity and overnutrition alter fetal growth rate and cotyledonary vascularity and angiogenic factor expression in the ewe. Am J Physiol Regul Integr Comp Physiol. 2010, 299: R249-258. 10.1152/ajpregu.00498.2009.PubMedCentralCrossRefPubMed
26.
Lea RG, Wooding P, Stewart I, Hannah LT, Morton S, Wallace K, Aitken RP, Milne JS, Regnault TR, Anthony RV, Wallace JM: The expression of ovine placental lactogen, StAR and progesterone-associated steroidogenic enzymes in placentae of overnourished growing adolescent ewes. Reproduction. 2007, 133: 785-796. 10.1530/REP-06-0294.CrossRefPubMed
27.
Mamluk R, Greber Y, Meidan R: Hormonal regulation of messenger ribonucleic acid expression for steroidogenic factor-1, steroidogenic acute regulatory protein, and cytochrome P450 side-chain cleavage in bovine luteal cells. Biol Reprod. 1999, 60: 628-634. 10.1095/biolreprod60.3.628.CrossRefPubMed
28.
Leyens G, Donnay I, Knoops B: Cloning of bovine peroxiredoxins-gene expression in bovine tissues and amino acid sequence comparison with rat, mouse and primate peroxiredoxins. Comp Biochem Physiol B Biochem Mol Biol. 2003, 136: 943-955. 10.1016/S1096-4959(03)00290-2.CrossRefPubMed
29.
Ashworth CJ, Sales DI, Wilmut I: Evidence of an association between the survival of embryos and the periovulatory plasma progesterone concentration in the ewe. J Reprod Fertil. 1989, 87: 28-32.
30.
Stronge AJ, Sreenan JM, Diskin MG, Mee JF, Kenny DA, Morris DG: Post-insemination milk progesterone concentrations and embryo survival in dairy cows. Theriogenology. 2005, 64: 1212-1224. 10.1016/j.theriogenology.2005.02.007.CrossRefPubMed
31.
McNeill RE, Diskin MG, Sreenan JM, Morris DG: Association between milk progesterone concentrations on different days and with embryo survival during the early luteal phase in dairy cows. Theriogenology. 2006, 65: 1435-1441. 10.1016/j.theriogenology.2005.08.015.CrossRefPubMed
32.
Meikle D, Westberg M: Maternal nutrition and reproduction of daughters in wild house mice (Mus musculus). Reproduction. 2001, 122: 437-442. 10.1530/rep.0.1220437.CrossRefPubMed
33.
Alejandro B, Pérez R, Pedrana G, Milton JT, Lopez A, Blackberry MA, Duncombe G, Rodriguez-Martinez H, Martin GB: Low maternal nutrition during pregnancy reduces the number of Sertoli cells in the newborn lamb. Reprod Fertil Dev. 2002, 14: 333-337. 10.1071/RD02046.CrossRefPubMed
34.
Smith DL, Stinefelt BM, Blemings KP, Wilson ME: Diet-induced alterations in progesterone clearance appear to be mediated by insulin signaling in hepatocytes. J Anim Sci. 2006, 84: 1102-1109.CrossRefPubMed
35.
George LA, Zhang L, Tuersunjiang N, Ma Y, Long NM, Uthlaut AB, Smith DT, Nathanielsz PW, Ford SP: Early maternal undernutrition programs increased feed intake, altered glucose metabolism and insulin secretion, and liver function, in aged female offspring. Am J Physiol Regul Integr Comp Physiol. 2012, 302: 795-804. 10.1152/ajpregu.00241.2011.CrossRef
36.
Herzog K, Voss C, Kastelic JP, Beindorff N, Paul V, Niemann H, Bollwein H: Luteal blood flow increases during the first three weeks of pregnancy in lactating dairy cows. Theriogenology. 2011, 75: 549-554. 10.1016/j.theriogenology.2010.09.024.CrossRefPubMed
37.
Berisha B, Schams D, Kosmann M, Amselgruber W, Einspanier R: Expression and tissue concentration of vascular endothelial growth factor, its receptors, and localization in thebovine corpus luteum during estrous cycle and pregnancy. Biol Reprod. 2000, 63: 1106-1114. 10.1095/biolreprod63.4.1106.CrossRefPubMed
38.
Schams D, Amselgruber W, Einspanier R, Sinowatz F, Gospodarowicz D: Localization and tissue concentrations of basic fibroblast growth factor in the bovine corpus luteum. Endocrine. 1994, 2: 907-912.
39.
Bernal AB, Vickers , Hampton MB, Poynton RA, Sloboda DM: Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. PLoS One. 2010, 5: e15558-10.1371/journal.pone.0015558.PubMedCentralCrossRefPubMed
Metadata
Title
Maternal nutrient restriction in the ewe from early to midgestation programs reduced steroidogenic enzyme expression and tended to reduce progesterone content of corpora lutea, as well as circulating progesterone in nonpregnant aged female offspring
Authors
Nathan M Long
Nuermaimaiti Tuersunjiang
Lindsey A George
Caleb O Lemley
Yan Ma
William J Murdoch
Peter W Nathanielsz
Stephen P Ford
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2013
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-11-34

Other articles of this Issue 1/2013

Reproductive Biology and Endocrinology 1/2013 Go to the issue

Research

Different effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro

Research

Differential expression of beta-catenin and dickkopf-1 in the third trimester placentas from normal and preeclamptic pregnancies: a comparative study

Review

Endocrinology and physiology of pseudocyesis

Review

The management of Asherman syndrome: a review of literature

Research

Assessment of cells in the ascitic fluid of women with ovarian hyperstimulation syndrome: the clinical implications for subsequent ovarian malignancy

Research

A retrospective study on IVF/ICSI outcome in patients with anti-nuclear antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment