**Author details**

Maria Slomczynska1 , Malgorzata Grzesiak2 \* and Katarzyna Knapczyk-Stwora1

\*Address all correspondence to: m.grzesiak@ur.krakow.pl

1 Department of Endocrinology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland

2 Department of Animal Physiology and Endocrinology, University of Agriculture, Krakow, Poland

## **References**


[4] Schug TT, Janesick A, Blumberg B, Heindel JJ. Endocrine disrupting chemicals and disease susceptibility. Journal of Steroid Biochemistry and Molecular Biology. 2011;**127**:204- 215. DOI: 10.1016/j.jsbmb.2011.08.007

[18] Chevalier N, Paul-Bellon R, Camparo P, Michiels JF, Chevallier D, Fénichel P. Genetic variants of GPER/GPR30, a novel estrogen-related G protein receptor, are associated with human seminoma. International Journal of Molecular Sciences. 2014;**15**:1574-1789.

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

http://dx.doi.org/10.5772/intechopen.69220

213

[19] Thomas P. Characteristics of membrane progestin receptor alpha (mPRalpha) and progesterone membrane receptor component 1 (PGMRC1) and their roles in mediating rapid progestin actions. Frontiers in Neuroendocrinology. 2008;**29**:292-312. DOI:

[20] Pi M, Parrill AL, Quarles LD. GPRC6A mediates the non-genomic effects of steroids. Journal of Biological Chemistry. 2010;**285**:39953-39964. DOI: 10.1074/jbc.M110.158063

[21] Pascal LE, Wang Z. Unzipping androgen action through ZIP9: A novel membrane androgen receptor. Endocrinology. 2014;**155**:4120-4123. DOI: 10.1210/en.2014−1749

[22] Laurentino S, Pinto P, Correia S, Cavaco JE, Canário AVM, Socorro S. Structural variants of sex steroid hormone receptors in the testis: From molecular biology to physiological

[23] McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocrine

[24] Pepling ME. From primordial germ cell to primordial follicle: Mammalian female germ

[25] Sarraj MA, Drummond AE. Mammalian foetal ovarian development: Consequences for health and disease. Reproduction. 2012;**143**:151-163. DOI: 10.1530/REP-11-0247

[26] Pepling ME, Spradling AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Developmental Biology. 2001;**234**;339-351. DOI:

[27] McLaughlin EA, McIver SC. Awakening the oocyte: Controlling primordial follicle

[28] Hsueh AJ, Billig, H, Tsafriri A. Ovarian follicle atresia: A hormonally controlled apoptotic process. Endocrine Reviews. 1994;**15**:707-724. DOI: 10.1210/edrv-15-6-707

[29] Smith P, Wilhelm D, Rodgers RJ. Development of mammalian ovary. Journal of

[30] Fortune JE, Yang MY, Allen JJ, Herrick SL. Triennial reproduction symposium: The ovarian follicular reserve in cattle: What regulates its formation and size? Journal of Animal

[31] Ding W, Wang W, Zhou B, Zhang W, Huang P, Shi F, Taya K. Formation of primordial follicles and immunolocalization of PTEN, PKB and FOXO3A proteins in the ovaries of fetal and neonatal pigs. Journal of Reproduction and Development. 2010;**56**:162-168.

cell development. Genesis. 2006;**44**:622-632. DOI: 10.1002/dvg.20258

development. Reproduction. 2009;**137**:1-11. DOI: 10.1530/REP-08-0118

Endocrinology. 2014;**221**:R145-R161. DOI: 10.1530/JOE-14-0062

Science. 2013;**91**:3041-3050. DOI: 10.2527/jas.2013−6233

DOI: 10.3390/ijms15011574

10.1016/j.yfrne.2008.01.001

roles. OA Biotechnology. 2012;**1**:4

10.1006/dbio.2001.0269

DOI: 10.1262/jrd.09-094H

Reviews. 2000;**21**:200-214. DOI: 10.1210/edrv.21.2.0394


[18] Chevalier N, Paul-Bellon R, Camparo P, Michiels JF, Chevallier D, Fénichel P. Genetic variants of GPER/GPR30, a novel estrogen-related G protein receptor, are associated with human seminoma. International Journal of Molecular Sciences. 2014;**15**:1574-1789. DOI: 10.3390/ijms15011574

[4] Schug TT, Janesick A, Blumberg B, Heindel JJ. Endocrine disrupting chemicals and disease susceptibility. Journal of Steroid Biochemistry and Molecular Biology. 2011;**127**:204-

[5] Björnström L, Sjöberg M. Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes. Molecular Endocrinology. 2005;**19**:833-

[6] Beato M, Klug J. Steroid hormone receptors: An update. Human Reproduction Update.

[7] Kumar R, Thompson EB. Transactivation functions of the N-terminal domains of nuclear hormone receptors: Protein folding and coactivator interactions. Molecular

[8] Rochette-Egly C. Nuclear receptors: Integration of multiple signalling pathways through phosphorylation. Cellular Signalling. 2003;**15**:355-366. DOI: 10.1016/S0898-6568(02)

[9] Khorasanizadeh S, Rastinejad F. Nuclear-receptor interactions on DNA-response elements. Trends in Biochemical Sciences. 2001;**26**:384-390. DOI: 10.1016/S0968-0004(01)

[10] Bunone G, Briand PA, Miksicek RJ, Picard D. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. EMBO

[11] Picard D, Bunone G, Liu JW, Donzé O. Steroid-independent activation of steroid receptors in mammalian and yeast cells and in breast cancer. Biochemical Society Transactions.

[12] Simons K, Toomre D. Lipid rafts and signal transduction. Nature Reviews Molecular

[13] Falkenstein E, Tillmann HC, Christ M, Feuring M, Wehling MC. Multiple actions of steroid hormones—A focus on rapid, nongenomic effects. Pharmacological Reviews.

[14] Cato AC, Nestl A, Mink S. Rapid actions of steroid receptors in cellular signaling path-

[15] Liao RS, Ma S, Miao L, Li R, Yin Y, Raj GV. Androgen receptor-mediated non-genomic regulation of prostate cancer cell proliferation. Translational Andrology and Urology.

[16] Leitman DC, Paruthiyil S, Yuan C, Herber CB, Olshansky M, Tagliaferri M, Cohen I, Speed TP. Tissue-specific regulation of genes by estrogen receptors. Seminars in

[17] Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science. 2005;**307**:1625-1630.

215. DOI: 10.1016/j.jsbmb.2011.08.007

2000;**6**:225-236. DOI: 10.1093/humupd/6.3.225

Endocrinology. 2003;**17**:1-10. DOI: 10.1210/me.2002−0258

842. DOI: 10.1210/me.2004−0486

00115-8

212 Selected Topics in Neonatal Care

01800-X

Journal. 1996;**15**:2174-2183

2000;**52**:513-556

DOI: 10.1126/science.1106943

1997;**25**:597-602. DOI: 10.1042/bst0250597

Cell Biology. 2000;**1**:31-39. DOI: 10.1038/35036052

ways. Sci STKE. 2002;**2002**:re9. DOI: 10.1126/stke.2002.138.re9

Reproductive Medicine. 2012;**30**:14-22. DOI: 10.1055/s-0031-1299593

2013;**2**:187-196. DOI: 10.3978/j.issn.2223-4683.2013.09.07


[32] McNatty KP, Smith P, Hudson NL, Heath DA, Tisdall DJ, O WS, Braw-Tal R. Development of the sheep ovary during fetal and early neonatal life and the effect of fecundity genes. Journal of Reproduction and Fertility. Supplement. 1995;**49**:123-135

[43] Kezele P, Skinner MK. Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: Endocrine model of follicle assembly. Endocrinology.

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

http://dx.doi.org/10.5772/intechopen.69220

215

[44] Nilsson EE, Skinner MK. Progesterone regulation of primordial follicle assembly in bovine fetal ovaries. Molecular and Cellular Endocrinology. 2009;**313**:9-16. DOI:

[45] Dutta S, Mark-Kappeler CJ, Hoyer PB and Pepling ME. The steroid hormone environment during primordial follicle formation in perinatal mouse ovaries. Biology of

[46] Wang C, Roy SK. Development of primordial follicles in the hamster: Role of estradiol-

[47] Ikeda Y, Nagai A, Ikeda MA, Hayashi S. Neonatal estrogen exposure inhibits steroidogenesis in the developing rat ovary. Developmental Dynamics. 2001;**221**:443-453. DOI:

[48] Britt KL, Saunders PK, McPherson SJ, Misso ML, Simpson ER, Findlay JK. Estrogen actions on follicle formation and early follicle development. Biology of Reproduction.

[49] Zachos NC, Billiar RB, Albrecht ED, Pepe GJ. Developmental regulation of baboon fetal ovarian maturation by estrogen. Biology of Reproduction. 2002;**67**:1148-1156. DOI:

[50] Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. Journal of Clinical Investigation.

[51] Steckler T, Manikkam M, Inskeep EK, Padmanabhan V. Developmental programming: Follicular persistence in prenatal testosterone-treated sheep is not programmed by androgenic actions of testosterone. Endocrinology. 2007;**148**:3532-3540. DOI: 10.1210/

[52] Hogg K, McNeilly AS, Duncan WC. Prenatal androgen exposure leads to alterations in gene and protein expression in the ovine fetal ovary. Endocrinology. 2011;**152**:2048-2059.

[53] Abbott DH, Dumesic DA, Franks S. Developmental origin of polycystic ovary syndrome— A hypothesis. Journal of Endocrinology. 2002;**174**:1-5. DOI: 10.1677/joe.0.1740001 [54] Tyndall V, Broyde M, Sharpe R, Welsh M, Drake AJ, McNeilly AS. Effect of androgen treatment during foetal and/or neonatal life on ovarian function in prepubertal and

[55] Ongaro L, Salvetti NR, Giovambattista A, Spinedi E, Ortega HH. Neonatal androgenization-induced early endocrine-metabolic and ovary misprogramming in the female rat.

adult rats. Reproduction. 2012;**143**:21-33. DOI: 10.1530/REP-11-0239

Life Sciences. 2015;**130**:66-72. DOI: 10.1016/j.lfs.2015.03.008

Reproduction. 2014;**91**:68:1-12. DOI: 10.1095/biolreprod.114.119214

2004;**71**:1712-1723. DOI: 10.1095/biolreprod.104.028175

17beta. Endocrinology. 2007;**148**:1707-1716. DOI: 10.1210/en.2006-1193

2003;**144**:3329-3337. DOI: 10.1210/en.2002−0131

10.1016/j.mce.2009.09.004

10.1002/dvdy.1162

en.2007-0339

10.1095/biolreprod67.4.1148

DOI: 10.1210/en.2010-1219

1998;**101**:2622-2629. DOI: 10.1172/JCI2081


[43] Kezele P, Skinner MK. Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: Endocrine model of follicle assembly. Endocrinology. 2003;**144**:3329-3337. DOI: 10.1210/en.2002−0131

[32] McNatty KP, Smith P, Hudson NL, Heath DA, Tisdall DJ, O WS, Braw-Tal R. Development of the sheep ovary during fetal and early neonatal life and the effect of fecundity genes.

[33] Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proceedings of the National Academy of Sciences of the

[34] Gervásio CG, Bernuci MP, Silva-de-Sá MF, Rosa-E-Silva AC. The role of androgen hormones in early follicular development. ISRN Obstetrics and Gynecology.

[35] Chang C, Lee SO, Wang RS, Yeh S, Chang TM. Androgen receptor (AR) physiological roles in male and female reproductive systems: Lessons learned from AR-knockout mice lacking AR in selective cells. Biology of Reproduction. 2013;**89**:21. DOI: 10.1095/

[36] Fowler PA, Anderson RA, Saunders PT, Kinnell H, Mason JI, Evans DB, Bhattacharya S, Flannigan S, Franks S, Monteiro A, O'Shaughnessy PJ. Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary. Journal of Clinical Endocrinology and Metabolism. 2011;**96**:1754-1762. DOI: 10.1210/jc.2010-2618

[37] Vendola K, Zhou J, Wang J, Famuyiwa OA, Bievre M, Bondy CA. Androgens promote oocyte insulin-like growth factor I expression and initiation of follicle development in the primate ovary. Biology of Reproduction. 1999;**61**:353-357. DOI: 10.1095/

[38] Yang MY, Fortune JE. Testosterone stimulates the primary to secondary follicle transition in bovine follicles in vitro. Biology of Reproduction. 2006;**75**:924-932. DOI: 10.1095/

[39] Yang JL, Zhang CP, Li L, Huang L, Ji SY, Lu CL, Fan CH, Cai H, Ren Y, Hu ZY, Gao F, Liu YX. Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis. Endocrinology. 2010;**151**:774-782. DOI: 10.1210/en.2009-0751

[40] Narkwichean A, Jayaprakasan K, Maalouf WE, Hernandez-Medrano JH, Pincott-Allen C, Campbell BK. Effects of dehydroepiandrosterone on in vivo ovine follicular develop-

[41] Rosenfeld CS, Murray AA, Simmer G, Hufford MG, Smith MF, Spears N, Lubahn DB. Gonadotropin induction of ovulation and corpus luteum formation in young estrogen receptor-alpha knockout mice. Biology of Reproduction. 2000;**62**:599-605. DOI: 10.1095/

[42] Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA, Smithies O. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proceedings of the National Academy of Sciences of the United

ment. Human Reproduction. 2014;**29**:146-154. DOI: 10.1093/humrep/det408

States of America. 1998;**95**:15677-15682. DOI: 10.1073/pnas.95.26.15677

Journal of Reproduction and Fertility. Supplement. 1995;**49**:123-135

2014;**2014**:818010. DOI: 10.1155/2014/818010

biolreprod.113.109132

214 Selected Topics in Neonatal Care

biolreprod61.2.353

biolreprod.106.051813

biolreprod62.3.599

United States of America. 2002;**99**:2890-2894. DOI: 10.1073/pnas.052658699


[56] Marcondes RR, Carvalho KC, Duarte DC, Garcia N, Amaral VC, Simões MJ, Lo Turco EG, Soares JM Jr, Baracat EC, Maciel GA. Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels. General and Comparative Endocrinology. 2015;**212**:28-33. DOI: 10.1016/j.ygcen.2015.01.006

[67] Bøgh IB, Christensen P, Dantzer V, Groot M, Thøfner IC, Rasmussen RK, Schmidt M, Greve T. Endocrine disrupting compounds: Effect of octylphenol on reproduction over three generations. Theriogenology. 2001;**55**:131-150. DOI: 10.1016/S0093-691X(00)00451-9

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

http://dx.doi.org/10.5772/intechopen.69220

217

[68] Wright C, Evans AC, Evans NP, Duffy P, Fox J, Boland MP, Roche JF, Sweeney T. Effect of maternal exposure to the environmental estrogen, octylphenol, during fetal and/or postnatal life on onset of puberty, endocrine status, and ovarian follicular dynamics in ewe lambs. Biology of Reproduction. 2002;**67**:1734-1740. DOI: 10.1095/biolreprod.101.002006

[69] Slomczynska M, Knapczyk-Stwora K, Grzesiak M, Koziorowski M, Nowak S. Androgen and estrogen imbalance affects folliculogenesis in the neonatal porcine ovary influencing cell proliferation and apoptosis. In: Abstracts from the translational reproductive biology and clinical reproductive endocrinology conference held November 17-20, 2016. Journal of Assisted Reproduction and Genetics. 2016;**33**:1693-1708. DOI: 10.1007/

[70] Vandenberg LN, Hauser R, Marcus M, Olea N, Welshons WV. Human exposure to bisphenol A (BPA). Reproductive Toxicology. 2007;**24**:139-177. DOI: 10.1016/j.reprotox.

[71] Zhou C, Wang W, Peretz J, Flaws JA. Bisphenol A exposure inhibits germ cell nest breakdown by reducing apoptosis in cultured neonatal mouse ovaries. Reproductive

[72] Suzuki A, Sugihara A, Uchida K, Sato T, Ohta Y, Katsu Y, Watanabe H, Iguchi T. Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice. Reproductive Toxicology. 2002;**16**:107-116. DOI:

[73] Otsuka F, Shimasaki S. A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: Its role in regulating granulosa cell mitosis. Proceedings of the National Academy of Sciences of the United States of America.

[74] Hutt KJ, McLaughlin EA, Holland MK. Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis. Molecular Human Reproduction.

[75] Rodríguez HA, Santambrosio N, Santamaría CG, Muñoz-de-Toro M, Luque EH. Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reproductive Toxicology. 2010;**30**:550-557. DOI: 10.1016/j.reprotox.2010.07.008

[76] Zhang HQ, Zhang XF, Zhang LJ, Chao HH, Pan B, Feng YM, Li L, Sun XF, Shen W. Fetal exposure to bisphenol A affects the primordial follicle formation by inhibiting the meiotic progression of oocytes. Molecular Biology Reports. 2012;**39**:5651-5657. DOI: 10.1007/

[77] Fernández M, Bourguignon N, Lux-Lantos V, Libertun C. Neonatal exposure to bisphenol a and reproductive and endocrine alterations resembling the polycystic ovarian

Toxicology. 2015;**57**:87-99. DOI: 10.1016/j.reprotox.2015.05.012

s10815-016-0827-9

10.1016/S0890-6238(02)00005-9

s11033-011-1372-3

2002;**99**:8060-8065. DOI: 10.1073/pnas.122066899

2006;**12**:61−69. DOI: 10.1093/molehr/gal010

2007.07.010


[67] Bøgh IB, Christensen P, Dantzer V, Groot M, Thøfner IC, Rasmussen RK, Schmidt M, Greve T. Endocrine disrupting compounds: Effect of octylphenol on reproduction over three generations. Theriogenology. 2001;**55**:131-150. DOI: 10.1016/S0093-691X(00)00451-9

[56] Marcondes RR, Carvalho KC, Duarte DC, Garcia N, Amaral VC, Simões MJ, Lo Turco EG, Soares JM Jr, Baracat EC, Maciel GA. Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels. General and Comparative

[57] Kemppainen JA, Lane MV, Sar M, Wilson EM. Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and

[58] O'Connor JC, Cook JC, Slone TW, Makovec GT, Frame SR, Davis LG. An ongoing validation of a Tier I screening battery for detecting endocrine-active compounds (EACs).

[59] Durlej M, Kopera I, Knapczyk-Stwora K, Hejmej A, Duda M, Koziorowski M, Slomczynska M, Bilinska B. Connexin 43 gene expression in male and female gonads of porcine offspring following in utero exposure to an anti-androgen, flutamide. Acta

[60] Kopera I, Durlej M, Hejmej A, Knapczyk-Stwora K, Duda M, Slomczynska M, Koziorowski M, Bilinska B. Effects of pre- and postnatal exposure to flutamide on connexin 43 expression in testes and ovaries of prepubertal pigs. European Journal of

[61] Durlej M, Knapczyk-Stwora K, Duda M, Kopera-Sobota I, Hejmej A, Bilinska B, Slomczynska M. Prenatal and neonatal exposure to the antiandrogen flutamide alters connexin 43 gene expression in adult porcine ovary. Domestic Animal Endocrinology.

[62] Grzesiak M, Knapczyk-Stwora K, Duda M, Slomczynska M. Elevated level of 17β-estradiol is associated with overexpression of FSHR, CYP19A1, and CTNNB1 genes in porcine ovarian follicles after prenatal and neonatal flutamide exposure. Theriogenology.

[63] Grzesiak M, Knapczyk-Stwora K, Luck MR, Mobasheri A, Slomczynska M. Effect of prenatal and neonatal anti-androgen flutamide treatment on aquaporin 5 expression in the adult porcine ovary. Reproduction in Domestic Animals. 2016;**51**:105-113. DOI: 10.1111/

[64] Durlej M, Knapczyk-Stwora K, Slomczynska M. Prenatal and neonatal flutamide administration increases proliferation and reduces apoptosis in large antral follicles of adult pigs. Animal Reproduction Science. 2012;**132**:58-65. DOI: 10.1016/j.anireprosci.2012.04.001 [65] Giger W, Brunner PH, Schaffner C. 4-Nonylphenol in sewage sludge: Accumulation of toxic metabolites from nonionic surfactants. Science. 1984;**225**:623-625. DOI: 10.1126/

[66] Katsuda S, Yoshida M, Watanabe G, Taya K, Maekawa A. Irreversible effects of neonatal exposure to p-tert-octylphenol on the reproductive tract in female rats. Toxicology and

Applied Pharmacology. 2000;**165**:217-226. DOI: 10.1006/taap.2000.8940

Endocrinology. 2015;**212**:28-33. DOI: 10.1016/j.ygcen.2015.01.006

antihormones. Journal of Biological Chemistry. 1992;**267**:968-974

Toxicological Sciences. 1998;**46**:45-60. DOI: 10.1006/toxs.1998.2550

Histochemica. 2011;**113**:6-12. DOI: 10.1016/j.acthis.2009.07.001

Histochemistry. 2010;**54**:e15. DOI: 10.4081/ejh.2010.e15

2011;**40**:19-29. DOI: 10.1016/j.domaniend.2010.08.003

rda.12652

216 Selected Topics in Neonatal Care

science.6740328

2012;**78**:2050-2060. DOI: 10.1016/j.theriogenology.2012.07.026


syndrome in adult rats. Environmental Health Perspectives. 2010;**118**:1217-1222. DOI: 10.1289/ehp.0901257

[89] Patel S, Zhou C, Rattan S, Flaws JA. Effects of endocrine-disrupting chemicals on the ovary. Biology of Reproduction. 2015;**93**:1-9. DOI: 10.1095/biolreprod.115.130336

Endocrine Active Compounds Actions during Neonatal Period: Effect on the Ovary

http://dx.doi.org/10.5772/intechopen.69220

219

[90] Gaido KW, Maness SC, McDonnell DP, Dehal SS, Kupfer D, Safe S. Interaction of methoxychlor and related compounds with estrogen receptor α and β, and androgen receptor: Structure-activity studies. Molecular Pharmacology. 2000;**58**:852-858. DOI:

[91] Uzumcu M, Kuhn PE, Marano JE, Armenti AE, Passantino L. Early postnatal methoxychlor exposure inhibits folliculogenesis and stimulates anti-Mullerian hormone production in the rat ovary. Journal of Endocrinology. 2006;**191**:549-558. DOI: 10.1677/

[92] Armenti AE, Zama AM, Passantino L, Uzumcu M. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats. Toxicology and Applied Pharmacology. 2008;**233**:286-296. DOI:

[93] Zama AM, Uzumcu M. Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes epigenetic alterations in adult ovarian genes. Endocrinology. 2009;**150**:4681-4691.

10.1124/mol.58.4.852

10.1016/j.taap.2008.09.010

DOI: 10.1210/en.2009−0499

joe.1.06592


[89] Patel S, Zhou C, Rattan S, Flaws JA. Effects of endocrine-disrupting chemicals on the ovary. Biology of Reproduction. 2015;**93**:1-9. DOI: 10.1095/biolreprod.115.130336

syndrome in adult rats. Environmental Health Perspectives. 2010;**118**:1217-1222. DOI:

[78] Kim H, Nakajima T, Hayashi S, Chambon P, Watanabe H, Iguchi T, Sato T. Effects of diethylstilbestrol on programmed oocyte death and induction of polyovular follicles in neonatal mouse ovaries. Biology of Reproduction. 2009;**81**:1002-1009. DOI: 10.1095/

[79] Alwis ID, Maroni DM, Hendry IR, Roy SK, May JV, Leavitt WW, Hendry WJ. Neonatal diethylstilbestrol exposure disrupts female reproductive tract structure/function via both direct and indirect mechanisms in the hamster. Reproductive Toxicology. 2011;**32**:472-483.

[80] Karavan JR, Pepling ME. Effects of estrogenic compounds on neonatal oocyte development. Reproductive Toxicology. 2012;**34**:51-56. DOI: 10.1016/j.reprotox.2012.02.005 [81] Rivera OE, Varayoud J, Rodríguez HA, Muñoz-de-Toro M, Luque EH. Neonatal exposure to bisphenol A or diethylstilbestrol alters the ovarian follicular dynamics in the lamb. Reproductive Toxicology. 2011;**32**:304-312. DOI: 10.1016/j.reprotox.2011.06.118 [82] Jefferson W, Newbold R, Padilla-Banks E, Pepling M. Neonatal genistein treatment alters ovarian differentiation in the mouse: Inhibition of oocyte nest breakdown and increased oocyte survival. Biology of Reproduction. 2006;**74**:161-168. DOI: 10.1095/

[83] Jefferson WN, Doerge D, Padilla-Banks E, Woodling KA, Kissling GE, Newbold R. Oral exposure to genistin, the glycosylated form of genistein, during neonatal life adversely affects the female reproductive system. Environmental Health Perspectives.

[84] Zhang T, Li L, Qin XS, Zhou Y, Zhang XF, Wang LQ, De Felici M, Chen H, Qin GQ, Shen W. Di-(2-ethylhexyl)phthalate and bisphenol A exposure impairs mouse primordial follicle assembly in vitro. Environmental and Molecular Mutagenesis. 2014;**55**:343-353.

[85] Zhang XF, Zhang LJ, Li L, Feng YN, Chen B, Ma JM, Huynh E, Shi QH, De Felici M, Shen W. Diethylhexyl phthalate exposure impairs follicular development and affects oocyte maturation in the mouse. Environmental and Molecular Mutagenesis. 2013;**54**:354-361.

[86] Wakeling AE, Dukes M, Bowler J. A potent specific pure antiestrogen with clinical poten-

[87] Chen Y, Breen K, Pepling ME. Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse

[88] Ahn HJ, An BS, Jung EM, Yang H, Choi KC, Jeung EB. Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats. Molecular

ovary. Journal of Endocrinology. 2009;**202**:407-417. DOI: 10.1677/JOE-09-0109

Reproduction and Development. 2012;**79**:626-636. DOI: 10.1002/mrd.22070

10.1289/ehp.0901257

218 Selected Topics in Neonatal Care

biolreprod.108.070599

biolreprod.105.045724

DOI: 10.1002/em.21847

DOI: 10.1002/em.21776

tial. Cancer Research. 1991;**51**:3867-3873

DOI: 10.1016/j.reprotox.2011.09.006

2009;**117**:1883-1889. DOI: 10.1289/ehp.0900923


**Chapter 14**

**Provisional chapter**

**Reducing Early Neonatal Mortality in Nigeria—The**

The West African nation of Nigeria seems to have run out of ideas on how their neonatal mortality rate may be lowered. This situation has become dare as the country could not make any significant progress even with the great supports of the last 10 years of Millennium Development Goal. Presently, one in every two deceased child under 5 years of age in Nigeria is a neonate. Literature reveals that most of these deceased neonates are classified preterm or low birthweight, of which nearly four in five must die within first 7 days. This clearly identified the categories and stages of highest mortality; however, it is disappointing that the authorities of the Nigerian health care system have for too long been unable to devise a solution for the neonates. Probably, inadequacy of climatic and cultural compatibilities might partly be responsible for the failure of their current conventional ideas and technologies—these being predominantly imported. Yet, there seems to be lack of interest in some home-grown unconventional ideas that have achieved the needed reduction at few centers. In this chapter, we present the unconventional approaches and encourage across-the-nation translation of the applications to

**Keywords:** neonate, Nigeria, neonatal mortality, innovative technique, thermal distress

Neonatology in the West African sub region, especially in Nigeria, will remain in a state of "scientific comma" until a decisive solution is found to reverse her high neonatal mortality that has continued to be the highest in the world. The solutions required might not necessarily be conventional, as practiced in developed countries of the world, since such imported

**Reducing Early Neonatal Mortality in Nigeria—The** 

DOI: 10.5772/intechopen.69221

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

Hippolite O. Amadi and Mohammed B. Kawuwa

Additional information is available at the end of the chapter

achieve accelerated end to this situation.

Additional information is available at the end of the chapter

Hippolite O. Amadi and Mohammed B.

http://dx.doi.org/10.5772/intechopen.69221

**Abstract**

**1. Introduction**

**Solution**

Kawuwa

**Solution**

**Provisional chapter**
