Inter- and trans-generational effects of gestational ghrelin imbalance on development and reproduction in the mouse
Pedro Javier Torres A , Eugenia Mercedes Luque A , Nicolás David Ramírez A , Valeria Paola Carlini A and Ana Carolina Martini
A *
+ Author Affiliations
- Author Affiliations
A Instituto de Fisiología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, INICSA (CONICET-FCM), Santa Rosa 1085, X5000ESU Córdoba, Argentina.
Reproduction, Fertility and Development 34(14) 944-955 https://doi.org/10.1071/RD22104
Published online: 29 August 2022
© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing
Abstract
Context and aims: We have demonstrated that ghrelin (Ghrl) participates in fetal programming, since intragestational hyperghrelinaemia increased pup’s growth and a Ghrl-receptor antagonist accelerated offspring’s sexual maturation and impaired their adult reproductive function. Now, we aim to analyse if these phenotypic changes (found in F1) also occurred in F2 and/or F3 generations.
Methods: We treated mice dams (F0), with 4 nmol/animal/day of Ghrl or 6 nmol/animal/day of an antagonist [Ant:(d-Lys3)GHRP6] from day 1 of pregnancy until delivery. When F1 female pups reached adulthood, they were paired to obtain F2, and subsequently, F2 females were paired to obtain F3. Parameters evaluated in F2 and F3 pups were: growth, physical development, neurobiological maturation, puberty onset and in adulthood, reproductive function.
Key results: The F2 and F3 Ant groups showed a significant increase in litter size. Although no differences were detected in the weight of these pups at birth, in adulthood, they were heavier. At F3, pups from the Ant group showed advanced incisors eruption and eye opening compared to controls. Furthermore, F3 male pups from the Ant group showed earlier testis descent, although in adulthood, these males exhibited reduced sperm concentration in comparison to Ghrl. No differences were detected in F2 or F3 females regarding puberty onset or reproduction.
Conclusions and implications: Some fetal programming effects of Ghrl seen in F1, also appeared transgenerationally. Since many women at reproductive age suffer from conditions with reduced Ghrl levels (i.e. obesity or polycystic ovarian syndrome), these results could be relevant to the health of their descendants.
Keywords: development, fetal programming, growth, litter size, pregnancy, puberty, reproduction, reprogramming, sperm.
References
Anway, MD, Cupp, AS, Uzumcu, M, and Skinner, MK (2005). Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308, 1466–1469.| Epigenetic transgenerational actions of endocrine disruptors and male fertility.Crossref | GoogleScholarGoogle Scholar |
Anway, MD, Leathers, C, and Skinner, MK (2006a). Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 147, 5515–5523.
| Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease.Crossref | GoogleScholarGoogle Scholar |
Anway, MD, Memon, MA, Uzumcu, M, and Skinner, MK (2006b). Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis. Journal of Andrology 27, 868–879.
| Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis.Crossref | GoogleScholarGoogle Scholar |
Anway, MD, Rekow, SS, and Skinner, MK (2008). Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis. Reproductive Toxicology 26, 100–106.
| Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis.Crossref | GoogleScholarGoogle Scholar |
Avendaño, MS, Vazquez, MJ, and Tena-Sempere, M (2017). Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty. Human Reproduction Update 23, 737–763.
| Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty.Crossref | GoogleScholarGoogle Scholar |
Bedford, JM, Calvin, H, and Cooper, GW (1973). The maturation of spermatozoa in the human epididymis. Journal of Reproduction and Fertility Supplement 18, 199–213.
Bertoldi, ML, Luque, EM, Carlini, VP, Vincenti, LM, Stutz, G, Santillán, ME, Ruiz, RD, Fiol de Cuneo, M, and Martini, AC (2011). Inhibitory effects of ghrelin on sexual behavior: role of the peptide in the receptivity reduction induced by food restriction in mice. Hormone and Metabolic Research 43, 494–499.
| Inhibitory effects of ghrelin on sexual behavior: role of the peptide in the receptivity reduction induced by food restriction in mice.Crossref | GoogleScholarGoogle Scholar |
Bowers, WJ, Nakai, S, Chu, I, Wade, MG, Moir, D, Yagminas, A, Gill, S, Pulido, O, and Meuller, R (2004). Early developmental neurotoxicity of a PCB/organochlorine mixture in rodents after gestational and lactational exposure. Toxicological Sciences 77, 51–62.
| Early developmental neurotoxicity of a PCB/organochlorine mixture in rodents after gestational and lactational exposure.Crossref | GoogleScholarGoogle Scholar |
Chadio, S, and Kotsampasi, B (2014). The role of early life nutrition in programming of reproductive function. Journal of Developmental Origins of Health and Disease 5, 2–15.
| The role of early life nutrition in programming of reproductive function.Crossref | GoogleScholarGoogle Scholar |
Chanoine, J-P, Wong, ACK, and Barrios, V (2006). Obestatin, acylated and total ghrelin concentrations in the perinatal rat pancreas. Hormone Research in Paediatrics 66, 81–88.
| Obestatin, acylated and total ghrelin concentrations in the perinatal rat pancreas.Crossref | GoogleScholarGoogle Scholar |
Cooper T (1999) Epididymis. In ‘Encyclopedia of reproduction. Vol. 8’. (Eds E Knobil, JD Neill) pp. 1–17. (Academic Press)
Cornwall, GA, Vindivich, D, Tillman, S, and Chang, TSK (1988). The effect of sulfhdryl oxidation on the morphology of immature hamster epididymal spermatozoa induced to acquire motility in vitro. Biology of Reproduction 39, 141–155.
| The effect of sulfhdryl oxidation on the morphology of immature hamster epididymal spermatozoa induced to acquire motility in vitro.Crossref | GoogleScholarGoogle Scholar |
De Bond, J-AP, and Smith, JT (2014). Kisspeptin and energy balance in reproduction. Reproduction 147, R53–R63.
| Kisspeptin and energy balance in reproduction.Crossref | GoogleScholarGoogle Scholar |
Desai, M, Gayle, D, Babu, J, and Ross, MG (2005). Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 288, R91–R96.
| Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition.Crossref | GoogleScholarGoogle Scholar |
Doyle, TJ, Bowman, JL, Windell, VL, McLean, DJ, and Kim, KH (2013). Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice. Biology of Reproduction 88, 1–15.
| Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice.Crossref | GoogleScholarGoogle Scholar |
Du, C, Li, H, Cao, G, Xilingaowa Wang, C, and Li, C (2010). Expression of the orexigenic peptide ghrelin and the type 1a growth hormone secretagogue receptor in sheep oocytes and pre-implantation embryos produced in vitro. Reproduction in Domestic Animals 45, 92–98.
| Expression of the orexigenic peptide ghrelin and the type 1a growth hormone secretagogue receptor in sheep oocytes and pre-implantation embryos produced in vitro.Crossref | GoogleScholarGoogle Scholar |
Fernandez-Fernandez, R, Martini, AC, Navarro, VM, Castellano, JM, Dieguez, C, Aguilar, E, Pinilla, L, and Tena-Sempere, M (2006). Novel signals for the integration of energy balance and reproduction. Molecular and Cellular Endocrinology 254–255, 127–132.
| Novel signals for the integration of energy balance and reproduction.Crossref | GoogleScholarGoogle Scholar |
Fernández-Fernández, R, Tena-Sempere, M, Navarro, VM, Barreiro, ML, Castellano, JM, Aguilar, E, and Pinilla, L (2005). Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies. Neuroendocrinology 82, 245–255.
| Effects of ghrelin upon gonadotropin-releasing hormone and gonadotropin secretion in adult female rats: in vivo and in vitro studies.Crossref | GoogleScholarGoogle Scholar |
Fuglsang, J, Skjærbæk, C, Espelund, U, Frystyk, J, Fisker, S, Flyvbjerg, A, and Ovesen, P (2005). Ghrelin and its relationship to growth hormones during normal pregnancy. Clinical Endocrinology 62, 554–559.
| Ghrelin and its relationship to growth hormones during normal pregnancy.Crossref | GoogleScholarGoogle Scholar |
Gali Ramamoorthy, T, Begum, G, Harno, E, and White, A (2015). Developmental programming of hypothalamic neuronal circuits: impact on energy balance control. Frontiers in Neuroscience 9, 126–126.
| Developmental programming of hypothalamic neuronal circuits: impact on energy balance control.Crossref | GoogleScholarGoogle Scholar |
Gluckman, PD, Hanson, MA, and Spencer, HG (2005). Predictive adaptive responses and human evolution. Trends in Ecology & Evolution 20, 527–533.
| Predictive adaptive responses and human evolution.Crossref | GoogleScholarGoogle Scholar |
Gluckman, PD, Hanson, MA, Cooper, C, and Thornburg, KL (2008). Effect of in utero and early-life conditions on adult health and disease. New England Journal of Medicine 359, 61–73.
| Effect of in utero and early-life conditions on adult health and disease.Crossref | GoogleScholarGoogle Scholar |
Goebel-Stengel, M, Hofmann, T, Elbelt, U, Teuffel, P, Ahnis, A, Kobelt, P, Lambrecht, NWG, Klapp, BF, and Stengel, A (2013). The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index. Peptides 43, 13–19.
| The ghrelin activating enzyme ghrelin-O-acyltransferase (GOAT) is present in human plasma and expressed dependent on body mass index.Crossref | GoogleScholarGoogle Scholar |
Gualillo, O, Caminos, JE, Blanco, M, Garcìa-Caballero, T, Kojima, M, Kangawa, K, Dieguez, C, and Casanueva, FF (2001). Ghrelin, a novel placental-derived hormone. Endocrinology 142, 788–794.
| Ghrelin, a novel placental-derived hormone.Crossref | GoogleScholarGoogle Scholar |
Guerrero-Bosagna, C, Covert, TR, Haque, MM, Settles, M, Nilsson, EE, Anway, MD, and Skinner, MK (2012). Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers. Reproductive Toxicology 34, 694–707.
| Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.Crossref | GoogleScholarGoogle Scholar |
Hayashida, T, Nakahara, K, Mondal, MS, Date, Y, Nakazato, M, Kojima, M, Kangawa, K, and Murakami, N (2002). Ghrelin in neonatal rats: Distribution in stomach and its possible role. Journal of Endocrinology 173, 239–245.
| Ghrelin in neonatal rats: Distribution in stomach and its possible role.Crossref | GoogleScholarGoogle Scholar |
Heard, E, and Martienssen, RA (2014). Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95–109.
| Transgenerational epigenetic inheritance: myths and mechanisms.Crossref | GoogleScholarGoogle Scholar |
Hochberg, Z, Feil, R, Constancia, M, Fraga, M, Junien, C, Carel, J-C, Boileau, P, Le Bouc, Y, Deal, CL, Lillycrop, K, Scharfmann, R, Sheppard, A, Skinner, M, Szyf, M, Waterland, RA, Waxman, DJ, Whitelaw, E, Ong, K, and Albertsson-Wikland, K (2011). Child health, developmental plasticity, and epigenetic programming. Endocrine Reviews 32, 159–224.
| Child health, developmental plasticity, and epigenetic programming.Crossref | GoogleScholarGoogle Scholar |
Kihara, T, Surjono, TW, Sakamoto, M, Matsuo, T, Yasuda, Y, and Tanimura, T (2001). Effects of prenatal rubratoxin-B exposure on behaviors of mouse offspring. Toxicological Sciences 61, 368–373.
| Effects of prenatal rubratoxin-B exposure on behaviors of mouse offspring.Crossref | GoogleScholarGoogle Scholar |
Kojima, M, and Kangawa, K (2005). Ghrelin: structure and function. Physiological Reviews 85, 495–522.
| Ghrelin: structure and function.Crossref | GoogleScholarGoogle Scholar |
Kojima, M, Hosoda, H, Date, Y, Nakazato, M, Matsuo, H, and Kangawa, K (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660.
| Ghrelin is a growth-hormone-releasing acylated peptide from stomach.Crossref | GoogleScholarGoogle Scholar |
Kovács, A, and Foote, RH (1992). Viability and acrosome staining of bull, boar and rabbit spermatozoa. Biotechnic & Histochemistry 67, 119–124.
| Viability and acrosome staining of bull, boar and rabbit spermatozoa.Crossref | GoogleScholarGoogle Scholar |
Larson, JL, and Miller, DJ (1999). Simple histochemical stain for acrosomes on sperm from several species. Molecular Reproduction and Development 52, 445–449.
| Simple histochemical stain for acrosomes on sperm from several species.Crossref | GoogleScholarGoogle Scholar |
Luque, EM, Carlini, VP, Vincenti, LM, Puechagut, P, Stutz, G, Santillán, ME, Ruiz, RD, Martini, AC, and Fiol de Cuneo, M (2010). Effects of hexarelin (a ghrelin analogue) on fertilisation and the pre- and postnatal development of mice. Reproduction, Fertility and Development 22, 926–938.
| Effects of hexarelin (a ghrelin analogue) on fertilisation and the pre- and postnatal development of mice.Crossref | GoogleScholarGoogle Scholar |
Luque, EM, Torres, PJ, de Loredo, N, Vincenti, LM, Stutz, G, Santillan, ME, Ruiz, RD, de Cuneo, MF, and Martini, AC (2014). Role of ghrelin in fertilization, early embryo development, and implantation periods. Reproduction 148, 159–167.
| Role of ghrelin in fertilization, early embryo development, and implantation periods.Crossref | GoogleScholarGoogle Scholar |
Makler, A (1980). The improved ten-micrometer chamber for rapid sperm count and motility evaluation. Fertility and Sterility 33, 337–338.
| The improved ten-micrometer chamber for rapid sperm count and motility evaluation.Crossref | GoogleScholarGoogle Scholar |
Manikkam, M, Tracey, R, Guerrero-Bosagna, C, and Skinner, MK (2013). Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PloS One 8, e55387.
| Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.Crossref | GoogleScholarGoogle Scholar |
Martin, JR, Lieber, SB, McGrath, J, Shanabrough, M, Horvath, TL, and Taylor, HS (2011). Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming. Endocrinology 152, 2060–2066.
| Maternal ghrelin deficiency compromises reproduction in female progeny through altered uterine developmental programming.Crossref | GoogleScholarGoogle Scholar |
Metz, GA, and Schwab, ME (2004). Behavioral characterization in a comprehensive mouse test battery reveals motor and sensory impairments in growth-associated protein-43 null mutant mice. Neuroscience 129, 563–574.
| Behavioral characterization in a comprehensive mouse test battery reveals motor and sensory impairments in growth-associated protein-43 null mutant mice.Crossref | GoogleScholarGoogle Scholar |
Nakahara, K, Nakagawa, M, Baba, Y, Sato, M, Toshinai, K, Date, Y, Nakazato, M, Kojima, M, Miyazato, M, Kaiya, H, Hosoda, H, Kangawa, K, and Murakami, N (2006). Maternal ghrelin plays an important role in rat fetal development during pregnancy. Endocrinology 147, 1333–1342.
| Maternal ghrelin plays an important role in rat fetal development during pregnancy.Crossref | GoogleScholarGoogle Scholar |
Nilsson, EE, and Skinner, MK (2015). Environmentally induced epigenetic transgenerational inheritance of reproductive disease. Biology of Reproduction 93, 1–8.
| Environmentally induced epigenetic transgenerational inheritance of reproductive disease.Crossref | GoogleScholarGoogle Scholar |
Nilsson, EE, Sadler-Riggleman, I, and Skinner, MK (2018). Environmentally induced epigenetic transgenerational inheritance of disease. Environmental Epigenetics 4, dvy016.
| Environmentally induced epigenetic transgenerational inheritance of disease.Crossref | GoogleScholarGoogle Scholar |
Puttabyatappa M, Padmanabhan V (2018) Developmental programming of ovarian functions and dysfunctions. In ‘Vitamins and hormones. Vol. 107’. (Ed. G Litwack) pp. 377–422. (Academic Press)
| Crossref |
Rabadán-Diehl, C, and Nathanielsz, P (2013). From mice to men: research models of developmental programming. Journal of Developmental Origins of Health and Disease 4, 3–9.
| From mice to men: research models of developmental programming.Crossref | GoogleScholarGoogle Scholar |
Rak-Mardyła, A, Gregoraszczuk, EL, Karpeta, A, and Duda, M (2012). Expression of ghrelin and the ghrelin receptor in different stages of porcine corpus luteum development and the inhibitory effects of ghrelin on progesterone secretion, 3β-hydroxysteroid dehydrogenase (3β-honestly significant difference (HSD)) activity and protein expression. Theriogenology 77, 1505–1512.
| Expression of ghrelin and the ghrelin receptor in different stages of porcine corpus luteum development and the inhibitory effects of ghrelin on progesterone secretion, 3β-hydroxysteroid dehydrogenase (3β-honestly significant difference (HSD)) activity and protein expression.Crossref | GoogleScholarGoogle Scholar |
Repaci, A, Gambineri, A, Pagotto, U, and Pasquali, R (2011). Ghrelin and reproductive disorders. Molecular and Cellular Endocrinology 340, 70–79.
| Ghrelin and reproductive disorders.Crossref | GoogleScholarGoogle Scholar |
Sabatini, L, Young, E, Inza, R, Paz, D, Marconi, G, and Lombardi, E (2009). Importancia de los niveles de Ghrelina, estado nutricional y BMI como marcadores predictivos de embarazo en un programa de FIV (fertilización in vitro). Reproducción 24, 51–55.
Sadler-Riggleman, I, Klukovich, R, Nilsson, E, Beck, D, Xie, Y, Yan, W, and Skinner, MK (2019). Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility. Environmental Epigenetics 5, dvz013.
| Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility.Crossref | GoogleScholarGoogle Scholar |
Sato, M, Nakahara, K, Goto, S, Kaiya, H, Miyazato, M, Date, Y, Nakazato, M, Kangawa, K, and Murakami, N (2006). Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord. Biochemical and Biophysical Research Communications 350, 598–603.
| Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord.Crossref | GoogleScholarGoogle Scholar |
Schneider, JE (2004). Energy balance and reproduction. Physiology & Behavior 81, 289–317.
| Energy balance and reproduction.Crossref | GoogleScholarGoogle Scholar |
Shibata, K, Hosoda, H, Kojima, M, Kangawa, K, Makino, Y, Makino, I, Kawarabayashi, T, Futagami, K, and Gomita, Y (2004). Regulation of ghrelin secretion during pregnancy and lactation in the rat: possible involvement of hypothalamus. Peptides 25, 279–287.
| Regulation of ghrelin secretion during pregnancy and lactation in the rat: possible involvement of hypothalamus.Crossref | GoogleScholarGoogle Scholar |
Skinner, MK, Manikkam, M, Tracey, R, Guerrero-Bosagna, C, Haque, M, and Nilsson, EE (2013). Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. BMC Medicine 11, 228.
| Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity.Crossref | GoogleScholarGoogle Scholar |
Steculorum, SM, and Bouret, SG (2011). Developmental effects of ghrelin. Peptides 32, 2362–2366.
| Developmental effects of ghrelin.Crossref | GoogleScholarGoogle Scholar |
Tanaka, K, Minoura, H, Isobe, T, Yonaha, H, Kawato, H, Wang, DF, Yoshida, T, Kojima, M, Kangawa, K, and Toyoda, N (2003). Ghrelin is involved in the decidualization of human endometrial stromal cells. The Journal of Clinical Endocrinology & Metabolism 88, 2335–2340.
| Ghrelin is involved in the decidualization of human endometrial stromal cells.Crossref | GoogleScholarGoogle Scholar |
Tawadros, N, Salamonsen, LA, Dimitriadis, E, and Chen, C (2007). Facilitation of decidualization by locally produced ghrelin in the human endometrium. Molecular Human Reproduction 13, 483–489.
| Facilitation of decidualization by locally produced ghrelin in the human endometrium.Crossref | GoogleScholarGoogle Scholar |
Tena-Sempere, M (2007). Ghrelin and reproduction: ghrelin as novel regulator of the gonadotropic axis. Vitamins & Hormones 77, 285–300.
| Ghrelin and reproduction: ghrelin as novel regulator of the gonadotropic axis.Crossref | GoogleScholarGoogle Scholar |
Tena-Sempere, M (2008). Ghrelin as a pleotrophic modulator of gonadal function and reproduction. Nature Clinical Practice Endocrinology & Metabolism 4, 666–674.
| Ghrelin as a pleotrophic modulator of gonadal function and reproduction.Crossref | GoogleScholarGoogle Scholar |
Torres, PJ, Luque, EM, Ponzio, MF, Cantarelli, V, Diez, M, Figueroa, S, Vincenti, LM, Carlini, VP, and Martini, AC (2018). The role of intragestational ghrelin on postnatal development and reproductive programming in mice. Reproduction 156, 331–341.
| The role of intragestational ghrelin on postnatal development and reproductive programming in mice.Crossref | GoogleScholarGoogle Scholar |
Torres, PJ, Luque, EM, Di Giorgio, NP, Ramírez, ND, Ponzio, MF, Cantarelli, V, Carlini, VP, Lux-Lantos, V, and Martini, AC (2021). Fetal programming effects of a mild food restriction during pregnancy in mice: how does it compare to intragestational ghrelin administration? Reproductive Sciences 28, 3547–3561.
| Fetal programming effects of a mild food restriction during pregnancy in mice: how does it compare to intragestational ghrelin administration?Crossref | GoogleScholarGoogle Scholar |
Vorhees, CV, Butcher, RE, Brunner, RL, and Sobotka, TJ (1979). A developmental test battery for neurobehavioral toxicity in rats: a preliminary analysis using monosodium glutamate calcium carrageenan, and hydroxyurea. Toxicology and Applied Pharmacology 50, 267–282.
| A developmental test battery for neurobehavioral toxicity in rats: a preliminary analysis using monosodium glutamate calcium carrageenan, and hydroxyurea.Crossref | GoogleScholarGoogle Scholar |
Wang, X, Liang, L, and Du, L (2007). The effects of intrauterine undernutrition on pancreas ghrelin and insulin expression in neonate rats. Journal of Endocrinology 194, 121–129.
| The effects of intrauterine undernutrition on pancreas ghrelin and insulin expression in neonate rats.Crossref | GoogleScholarGoogle Scholar |
Wang, Z, Shen, M, Xue, P, DiVall, SA, Segars, J, and Wu, S (2018). Female offspring from chronic hyperandrogenemic dams exhibit delayed puberty and impaired ovarian reserve. Endocrinology 159, 1242–1252.
| Female offspring from chronic hyperandrogenemic dams exhibit delayed puberty and impaired ovarian reserve.Crossref | GoogleScholarGoogle Scholar |
Witham, EA, Meadows, JD, Shojaei, S, Kauffman, AS, and Mellon, PL (2012). Prenatal exposure to low levels of androgen accelerates female puberty onset and reproductive senescence in mice. Endocrinology 153, 4522–4532.
| Prenatal exposure to low levels of androgen accelerates female puberty onset and reproductive senescence in mice.Crossref | GoogleScholarGoogle Scholar |
Yoshida, S, Numachi, Y, Matsuoka, H, and Sato, M (2000). The absence of impairment of cliff avoidance reaction induced by subchronic methamphetamine treatment in inbred strains of mice. The Tohoku Journal of Experimental Medicine 190, 205–212.
| The absence of impairment of cliff avoidance reaction induced by subchronic methamphetamine treatment in inbred strains of mice.Crossref | GoogleScholarGoogle Scholar |
Zambrano, E, Rodríguez-González, G, Guzmán, C, García-Becerra, R, Boeck, L, Díaz, L, Menjivar, M, Larrea, F, and Nathanielsz, PW (2005). A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development. The Journal of Physiology 563, 275–284.
| A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development.Crossref | GoogleScholarGoogle Scholar |
Zambrano, E, Guzmán, C, Rodríguez-González, GL, Durand-Carbajal, M, and Nathanielsz, PW (2014). Fetal programming of sexual development and reproductive function. Molecular and Cellular Endocrinology 382, 538–549.
| Fetal programming of sexual development and reproductive function.Crossref | GoogleScholarGoogle Scholar |
Zhang, K, Wei, H-X, Zhang, Y-H, Wang, S-H, Li, Y, Dai, Y-P, and Li, N (2007). Effects of ghrelin on in vitro development of porcine in vitro fertilized and parthenogenetic embryos. Journal of Reproduction and Development 53, 647–653.
| Effects of ghrelin on in vitro development of porcine in vitro fertilized and parthenogenetic embryos.Crossref | GoogleScholarGoogle Scholar |
