CLIMACTERIC 2015;18:1–3
Premature ovarian failure with 46,XX,t(1;4) (p34.1;q34): first case report and literature review P. Vichinsartvichai, C. Manolertthewan and P. Promrungrueng Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
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Key words: PREMATURE OVARIAN FAILURE, RECIPROCAL TRANSLOCATION, t(1;4)(p34.1;q34), PRIMARY OVARIAN INSUFFICIENCY
ABSTRACT Objectives To describe the first case of premature ovarian failure with a reciprocal translocation between chromosomes 1 and 4 and to review all the related literature. Methods A 39-year-old multigravida woman with secondary amenorrhea consulted for evaluation. High-resolution chromosomal evaluation, sonographic images of the reproductive organs and assessment of endogenous hormone production were performed. Results We identified a de novo balanced translocation 46,XX, t(1;4)(p34.1;q34) in our premature ovarian failure patient without other abnormalities of reproductive organs. Conclusions Most of the cases of premature ovarian failure are associated with the X chromosome. To the best of our knowledge, only 23 cases of autosomal abnormalities associated with premature ovarian failure have been reported and our case was the first with translocation between chromosomes 1 and 4. The cause of late-onset premature ovarian failure in our case might be associated with the caspase-3 gene, which is located on chromosome 4q34 and controls follicle apoptosis.
INTRODUCTION
CASE REPORT
Premature ovarian failure (POF) is a condition where women aged less than 40 years experience amenorrhea for at least 6 months with two serum follicle stimulating hormone (FSH) levels measured at least 1 month apart in the menopausal range1. The cause of POF in almost 70% of cases is idiopathic with normal chromosomal analysis. Other etiologies are pelvic radiation, pelvic surgery, autoimmunity, infection and single gene defect2. The remaining 10% are considered chromosomal abnormalities, most of which are associated with the X chromosome. Only 2% of POF cases are associated with autosomal abnormalities3–14. Most of these POF cases with autosomal abnormalities are thought to be coincidental9,12. In this report, we describe the first case of POF with balanced reciprocal translocation between chromosomes 1 and 4 with a literature review of possible explanations of gene involvement.
A 39-year-old multigravida, non-smoking, Thai woman in good health had consulted us for evaluation of amenorrhea for 2 years. She did not have vasomotor symptoms, vaginal dryness or loss of libido. Her body habitus was not changed over 2 years and she had normal vision. She had two children: an 8-year-old girl and a 6-year-old boy, and had not attempted to have another child. Previous childbirths were not complicated with postpartum hemorrhage. Her previous menstruation was regular without infrequent menstruation or abnormal uterine bleeding. Her menarche occurred at age 13 years. There was no history of pelvic surgery or radiation or infection. She did not take any form of contraception. Her family did not have a history of premature menopause. Initial evaluation, general physical examination and pelvic examination were unremarkable. Sonographic images of her pelvis revealed normal uterus and both ovaries were unremarkable. We performed a progesterone challenge test with
Correspondence: Dr P. Vichinsartvichai, Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Road, Dusit, Bangkok 10300, Thailand; E-mail: [email protected] CASE REPORT © 2015 International Menopause Society DOI: 10.3109/13697137.2014.992013
Received 10-11-2014 Revised 18-11-2014 Accepted 22-11-2014
Climacteric Downloaded from informahealthcare.com by University of Victoria on 02/25/15 For personal use only.
t(1;4) and premature ovarian failure medroxyprogesterone acetate 10 mg daily for 5 days and also then measured the patient’s serum hormone levels. Laboratory results found an elevated FSH level (88.2 mIU/ml) and a low level of estradiol (⬍ 10 pg/ml). Thyroid and prolactin studies were normal. Over the next 2 weeks, the patient came for a follow-up visit. Her progesterone challenge test was negative (no withdrawal bleeding). At that time, we counselled her that she had premature ovarian failure and her karyotype was procured from T lymphocytes extracted from peripheral blood using the common culture technique. The 30 metaphase lymphocytes were banded with the GTG-banding method and revealed a balanced translocation 46,XX,t(1;4)(p34.1;q34) (Figure 1). After reviewing the results of the studies and discussing the diagnosis and treatment options with the patient, she was prescribed sequential hormone therapy with estradiol 1 mg and dydrogesterone 10 mg. She has continued to follow up with our unit and has regular periods.
DISCUSSION Chromosomal abnormalities are frequently associated with POF and only a few of these abnormalities are associated with autosomal chromosome abnormalities9–14. To the best of our knowledge, there are only 23 cases of POF with autosomal abnormalities (Table 1). These abnormalities include nine Robertsonian translocations, nine reciprocal translocations and five chromosome inversions. Our case presented here is the ninth case of de novo reciprocal translocation.
Figure 1
2
Vichinsartvichai, Manolertthewan and Promrungrueng Table 1 Types of autosomal chromosome anomalies associated with premature ovarian failure that have been reported in the literature (n ⫽ 23) n (%) Robertsonian translocation 45,XX,der(13;14) 45,XX,der(14;21) 45,XX,der(15;22) Reciprocal translocation 46,XX,t(1;4)(p34.1;q34) 46,XX,t(2;11) 46,XX,t(6;15)(p21.3;q15) 46,XX,t(8;9)(p11.2;q12) 46,XX,t(2;15)(q32.3;q13.3) 46,XX,t(1;11)(q31;q25) 46,XX,t(8;9)(q22.1;p24.1) 46,XX,t(3;7)(q23;p12) 46,XX,t(4;5) Chromosome inversion 46,XX,i12(p12q12) 47,XX,⫹ i(9)(p10)[72]/46,XX[28] 46,XX,inv(3)(p11q12) 46,XX,inv(2)(p11.2q13)
9 5 3 1 9 1 1 1 1 1 1 1 1 1 5 2 1 1 1
(39.1) (21.8) (13.0) (4.4) (39.1) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (21.8) (8.7) (4.4) (4.4) (4.4)
References
3, 5, 10, 13, 14 9, 11 9 This report 3 4 4 6 7 8 12 12 11 13 14 14
The pathophysiology of POF falls into one of two categories: ovarian follicle dysfunction and accelerated depletion of primordial follicles2. Although many genes on the X chromosome govern the ovarian follicle function and apoptosis such as USP9X, ZFX, BMP15, SHOX, XIST, POF1B,
Karyotype 46,XX,t(1;4)(p34.1;q34)
Climacteric
Climacteric Downloaded from informahealthcare.com by University of Victoria on 02/25/15 For personal use only.
t(1;4) and premature ovarian failure DIAPH2, XPNPEP2 and FMR12, there are also many other genes on the autosome that control the apoptosis and function of the ovarian follicle such as BAX, BCL2, CDKN1B, CYP19A1, ESR1, FOXL2, CASP2 and CASP315. Considering the chromosome loci involved in our patient, there are 231 genes on locus 1p34.116 and 35 genes on locus 4q3417. After searching for each gene function that is located on these chromosome loci to find which gene might control the ovarian follicle function and apoptosis, we suspect that the caspase-3 gene (CASP3)18, which is located on 4q34 locus19, may be involved in our patient. The caspase-3 gene is a downstream endoprotease enzyme in the apoptosis pathway that inhibits the initial transition of the germ cell cyst to the primordial follicle15,20 and controls apoptosis of the granulosa cell of the ovarian follicle21–23. In the caspase-3 gene knockout mice ovary, apoptosis of the granulosa cell during follicular atresia fails to develop but apoptosis of the oocyte occurs normally22. The caspase-3 gene is also expressed in the human granulosa cell of follicular fluid from women undergoing oocyte retrieval for in vitro fertilization21. This gene function
Vichinsartvichai, Manolertthewan and Promrungrueng that partly governs the primordial follicle activation and granulosa cell apoptosis might elucidate how our patient could have had her reproductive function until she reached her late thirties. Moreover, there might be other factors or epigenetic controls in the nearby region of chromosome loci that activate caspase-3 function and accelerate follicular depletion in our case. In conclusion, the information about the genes that cause POF in cases of reciprocal autosomal translocation is still sparse. More studies about this issue could bring more understanding about POF and folliculogenesis that might help us prevent POF or treat infertile patients with diminished ovarian reserve. Optimizing menopausal hormone therapy for the POF patient until the average age of menopause should also be considered to decrease the risk of cardiovascular disease, osteoporosis and dementia24. Conflict of interest The authors report no confl ict of interest. The authors alone are responsible for the content and writing of this paper. Source of funding
Nil.
References 1. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009;360:606–14 2. Cox L, Liu JH. Primary ovarian insufficiency: an update. Int J Womens Health 2014;6:235–43 3. Hens L, Devroey P, Van Waesberghe L, Bonduelle M, Van Steirteghem AC, Liebaers I. Chromosome studies and fertility treatment in women with ovarian failure. Clin Genet 1989;36:81–91 4. Tupler R, Barbierato L, Larizza D, Sampaolo P, Piovella F, Maraschio P. Balanced autosomal translocations and ovarian dysgenesis. Hum Genet 1994;94:171–6 5. Kawano Y, Narahara H, Matsui N, Miyakawa I. Premature ovarian failure associated with a Robertsonian translocation. Acta Obstet Gynecol Scand 1998;77:467–9 6. Burton KA, Van Ee CC, Purcell K, Winship I, Shelling AN. Autosomal translocation associated with premature ovarian failure. J Med Genet 2000;37:E2 7. Tullu MS, Arora P, Parmar RC, Muranjan MN, Bharucha BA. Ovarian dysgenesis with balanced autosomal translocation. J Postgrad Med 2001;47:113–15 8. Sills ES, Harmon KE, Tucker MJ. First reported convergence of premature ovarian failure and cutis marmorata telangiectatica congenita. Fertil Steril 2002;78:1314–16 9. Portnoi MF, Aboura A, Tachdjian G, et al. Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients. Hum Reprod 2006;21:2329–34 10. Ceylaner G, Altinkaya SO, Mollamahmutoglu L, Ceylaner S. Genetic abnormalities in Turkish women with premature ovarian failure. Int J Gynaecol Obstet 2010;110:122–4 11. Lakhal B, Braham R, Berguigua R, et al. Cytogenetic analyses of premature ovarian failure using karyotyping and interphase fluorescence in situ hybridization (FISH) in a group of 1000 patients. Clin Genet 2010;78:181–5 12. Baronchelli S, Conconi D, Panzeri E, et al. Cytogenetics of premature ovarian failure: an investigation on 269 affected women. J Biomed Biotechnol 2011;2011:370195 13. Jiao X, Qin C, Li J, et al. Cytogenetic analysis of 531 Chinese women with premature ovarian failure. Hum Reprod 2012; 27:2201–7
Climacteric
14. Kalantari H, Madani T, Zari Moradi S, et al. Cytogenetic analysis of 179 Iranian women with premature ovarian failure. Gynecol Endocrinol 2013;29:588–91 15. Wood MA, Rajkovic A. Genomic markers of ovarian reserve. Semin Reprod Med 2013;31:399–415 16. Chromosome: 1 Map Location: 1p34: GenScript USA Inc.; 2014 [15 Sep 2014]. Available from: http://www.genscript.com/cgi-bin/ orf/browse.pl?species ⫽ 9606&type ⫽ locus&chromosome ⫽ 1&l ocus ⫽ 1p34&page ⫽ 1 17. Chromosome: 4 Map Location: 4q34: GenScript USA Inc.; 2014 [15 Sep 2014]. Available from: http://www.genscript.com/cgi-bin/ orf/browse.pl?species ⫽ 9606&type ⫽ locus&chromosome ⫽ 4&l ocus ⫽ 4q34 18. CASP3 caspase 3, apoptosis-related cysteine peptidase [Homo sapiens (human)]: HUGO gene nomenclature committee; 2014 [updated 11 Sep 2014]. Available from: http://www.ncbi.nlm.nih. gov/gene/836 19. Tiso N, Pallavicini A, Muraro T, et al. Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis. Biochem Biophys Res Commun 1996; 225:983–9 20. Choi Y, Ballow DJ, Xin Y, Rajkovic A. Lim homeobox gene, lhx8, is essential for mouse oocyte differentiation and survival. Biol Reprod 2008;79:442–9 21. Izawa M, Nguyen PH, Kim HH, Yeh J. Expression of the apoptosis-related genes, caspase-1, caspase-3, DNA fragmentation factor, and apoptotic protease activating factor-1, in human granulosa cells. Fertil Steril 1998;70:549–52 22. Matikainen T, Perez GI, Zheng TS, et al. Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. Endocrinology 2001;142: 2468–80 23. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 2013;5:a008656 24. de Villiers TJ, Pines A, Panay N, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 2013;16:316–37
3
Premature ovarian failure with 46,XX,t(1;4) (p34.1;q34): first case report and literature review P. Vichinsartvichai, C. Manolertthewan and P. Promrungrueng Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand
Climacteric Downloaded from informahealthcare.com by University of Victoria on 02/25/15 For personal use only.
Key words: PREMATURE OVARIAN FAILURE, RECIPROCAL TRANSLOCATION, t(1;4)(p34.1;q34), PRIMARY OVARIAN INSUFFICIENCY
ABSTRACT Objectives To describe the first case of premature ovarian failure with a reciprocal translocation between chromosomes 1 and 4 and to review all the related literature. Methods A 39-year-old multigravida woman with secondary amenorrhea consulted for evaluation. High-resolution chromosomal evaluation, sonographic images of the reproductive organs and assessment of endogenous hormone production were performed. Results We identified a de novo balanced translocation 46,XX, t(1;4)(p34.1;q34) in our premature ovarian failure patient without other abnormalities of reproductive organs. Conclusions Most of the cases of premature ovarian failure are associated with the X chromosome. To the best of our knowledge, only 23 cases of autosomal abnormalities associated with premature ovarian failure have been reported and our case was the first with translocation between chromosomes 1 and 4. The cause of late-onset premature ovarian failure in our case might be associated with the caspase-3 gene, which is located on chromosome 4q34 and controls follicle apoptosis.
INTRODUCTION
CASE REPORT
Premature ovarian failure (POF) is a condition where women aged less than 40 years experience amenorrhea for at least 6 months with two serum follicle stimulating hormone (FSH) levels measured at least 1 month apart in the menopausal range1. The cause of POF in almost 70% of cases is idiopathic with normal chromosomal analysis. Other etiologies are pelvic radiation, pelvic surgery, autoimmunity, infection and single gene defect2. The remaining 10% are considered chromosomal abnormalities, most of which are associated with the X chromosome. Only 2% of POF cases are associated with autosomal abnormalities3–14. Most of these POF cases with autosomal abnormalities are thought to be coincidental9,12. In this report, we describe the first case of POF with balanced reciprocal translocation between chromosomes 1 and 4 with a literature review of possible explanations of gene involvement.
A 39-year-old multigravida, non-smoking, Thai woman in good health had consulted us for evaluation of amenorrhea for 2 years. She did not have vasomotor symptoms, vaginal dryness or loss of libido. Her body habitus was not changed over 2 years and she had normal vision. She had two children: an 8-year-old girl and a 6-year-old boy, and had not attempted to have another child. Previous childbirths were not complicated with postpartum hemorrhage. Her previous menstruation was regular without infrequent menstruation or abnormal uterine bleeding. Her menarche occurred at age 13 years. There was no history of pelvic surgery or radiation or infection. She did not take any form of contraception. Her family did not have a history of premature menopause. Initial evaluation, general physical examination and pelvic examination were unremarkable. Sonographic images of her pelvis revealed normal uterus and both ovaries were unremarkable. We performed a progesterone challenge test with
Correspondence: Dr P. Vichinsartvichai, Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, 681 Samsen Road, Dusit, Bangkok 10300, Thailand; E-mail: [email protected] CASE REPORT © 2015 International Menopause Society DOI: 10.3109/13697137.2014.992013
Received 10-11-2014 Revised 18-11-2014 Accepted 22-11-2014
Climacteric Downloaded from informahealthcare.com by University of Victoria on 02/25/15 For personal use only.
t(1;4) and premature ovarian failure medroxyprogesterone acetate 10 mg daily for 5 days and also then measured the patient’s serum hormone levels. Laboratory results found an elevated FSH level (88.2 mIU/ml) and a low level of estradiol (⬍ 10 pg/ml). Thyroid and prolactin studies were normal. Over the next 2 weeks, the patient came for a follow-up visit. Her progesterone challenge test was negative (no withdrawal bleeding). At that time, we counselled her that she had premature ovarian failure and her karyotype was procured from T lymphocytes extracted from peripheral blood using the common culture technique. The 30 metaphase lymphocytes were banded with the GTG-banding method and revealed a balanced translocation 46,XX,t(1;4)(p34.1;q34) (Figure 1). After reviewing the results of the studies and discussing the diagnosis and treatment options with the patient, she was prescribed sequential hormone therapy with estradiol 1 mg and dydrogesterone 10 mg. She has continued to follow up with our unit and has regular periods.
DISCUSSION Chromosomal abnormalities are frequently associated with POF and only a few of these abnormalities are associated with autosomal chromosome abnormalities9–14. To the best of our knowledge, there are only 23 cases of POF with autosomal abnormalities (Table 1). These abnormalities include nine Robertsonian translocations, nine reciprocal translocations and five chromosome inversions. Our case presented here is the ninth case of de novo reciprocal translocation.
Figure 1
2
Vichinsartvichai, Manolertthewan and Promrungrueng Table 1 Types of autosomal chromosome anomalies associated with premature ovarian failure that have been reported in the literature (n ⫽ 23) n (%) Robertsonian translocation 45,XX,der(13;14) 45,XX,der(14;21) 45,XX,der(15;22) Reciprocal translocation 46,XX,t(1;4)(p34.1;q34) 46,XX,t(2;11) 46,XX,t(6;15)(p21.3;q15) 46,XX,t(8;9)(p11.2;q12) 46,XX,t(2;15)(q32.3;q13.3) 46,XX,t(1;11)(q31;q25) 46,XX,t(8;9)(q22.1;p24.1) 46,XX,t(3;7)(q23;p12) 46,XX,t(4;5) Chromosome inversion 46,XX,i12(p12q12) 47,XX,⫹ i(9)(p10)[72]/46,XX[28] 46,XX,inv(3)(p11q12) 46,XX,inv(2)(p11.2q13)
9 5 3 1 9 1 1 1 1 1 1 1 1 1 5 2 1 1 1
(39.1) (21.8) (13.0) (4.4) (39.1) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (4.4) (21.8) (8.7) (4.4) (4.4) (4.4)
References
3, 5, 10, 13, 14 9, 11 9 This report 3 4 4 6 7 8 12 12 11 13 14 14
The pathophysiology of POF falls into one of two categories: ovarian follicle dysfunction and accelerated depletion of primordial follicles2. Although many genes on the X chromosome govern the ovarian follicle function and apoptosis such as USP9X, ZFX, BMP15, SHOX, XIST, POF1B,
Karyotype 46,XX,t(1;4)(p34.1;q34)
Climacteric
Climacteric Downloaded from informahealthcare.com by University of Victoria on 02/25/15 For personal use only.
t(1;4) and premature ovarian failure DIAPH2, XPNPEP2 and FMR12, there are also many other genes on the autosome that control the apoptosis and function of the ovarian follicle such as BAX, BCL2, CDKN1B, CYP19A1, ESR1, FOXL2, CASP2 and CASP315. Considering the chromosome loci involved in our patient, there are 231 genes on locus 1p34.116 and 35 genes on locus 4q3417. After searching for each gene function that is located on these chromosome loci to find which gene might control the ovarian follicle function and apoptosis, we suspect that the caspase-3 gene (CASP3)18, which is located on 4q34 locus19, may be involved in our patient. The caspase-3 gene is a downstream endoprotease enzyme in the apoptosis pathway that inhibits the initial transition of the germ cell cyst to the primordial follicle15,20 and controls apoptosis of the granulosa cell of the ovarian follicle21–23. In the caspase-3 gene knockout mice ovary, apoptosis of the granulosa cell during follicular atresia fails to develop but apoptosis of the oocyte occurs normally22. The caspase-3 gene is also expressed in the human granulosa cell of follicular fluid from women undergoing oocyte retrieval for in vitro fertilization21. This gene function
Vichinsartvichai, Manolertthewan and Promrungrueng that partly governs the primordial follicle activation and granulosa cell apoptosis might elucidate how our patient could have had her reproductive function until she reached her late thirties. Moreover, there might be other factors or epigenetic controls in the nearby region of chromosome loci that activate caspase-3 function and accelerate follicular depletion in our case. In conclusion, the information about the genes that cause POF in cases of reciprocal autosomal translocation is still sparse. More studies about this issue could bring more understanding about POF and folliculogenesis that might help us prevent POF or treat infertile patients with diminished ovarian reserve. Optimizing menopausal hormone therapy for the POF patient until the average age of menopause should also be considered to decrease the risk of cardiovascular disease, osteoporosis and dementia24. Conflict of interest The authors report no confl ict of interest. The authors alone are responsible for the content and writing of this paper. Source of funding
Nil.
References 1. Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009;360:606–14 2. Cox L, Liu JH. Primary ovarian insufficiency: an update. Int J Womens Health 2014;6:235–43 3. Hens L, Devroey P, Van Waesberghe L, Bonduelle M, Van Steirteghem AC, Liebaers I. Chromosome studies and fertility treatment in women with ovarian failure. Clin Genet 1989;36:81–91 4. Tupler R, Barbierato L, Larizza D, Sampaolo P, Piovella F, Maraschio P. Balanced autosomal translocations and ovarian dysgenesis. Hum Genet 1994;94:171–6 5. Kawano Y, Narahara H, Matsui N, Miyakawa I. Premature ovarian failure associated with a Robertsonian translocation. Acta Obstet Gynecol Scand 1998;77:467–9 6. Burton KA, Van Ee CC, Purcell K, Winship I, Shelling AN. Autosomal translocation associated with premature ovarian failure. J Med Genet 2000;37:E2 7. Tullu MS, Arora P, Parmar RC, Muranjan MN, Bharucha BA. Ovarian dysgenesis with balanced autosomal translocation. J Postgrad Med 2001;47:113–15 8. Sills ES, Harmon KE, Tucker MJ. First reported convergence of premature ovarian failure and cutis marmorata telangiectatica congenita. Fertil Steril 2002;78:1314–16 9. Portnoi MF, Aboura A, Tachdjian G, et al. Molecular cytogenetic studies of Xq critical regions in premature ovarian failure patients. Hum Reprod 2006;21:2329–34 10. Ceylaner G, Altinkaya SO, Mollamahmutoglu L, Ceylaner S. Genetic abnormalities in Turkish women with premature ovarian failure. Int J Gynaecol Obstet 2010;110:122–4 11. Lakhal B, Braham R, Berguigua R, et al. Cytogenetic analyses of premature ovarian failure using karyotyping and interphase fluorescence in situ hybridization (FISH) in a group of 1000 patients. Clin Genet 2010;78:181–5 12. Baronchelli S, Conconi D, Panzeri E, et al. Cytogenetics of premature ovarian failure: an investigation on 269 affected women. J Biomed Biotechnol 2011;2011:370195 13. Jiao X, Qin C, Li J, et al. Cytogenetic analysis of 531 Chinese women with premature ovarian failure. Hum Reprod 2012; 27:2201–7
Climacteric
14. Kalantari H, Madani T, Zari Moradi S, et al. Cytogenetic analysis of 179 Iranian women with premature ovarian failure. Gynecol Endocrinol 2013;29:588–91 15. Wood MA, Rajkovic A. Genomic markers of ovarian reserve. Semin Reprod Med 2013;31:399–415 16. Chromosome: 1 Map Location: 1p34: GenScript USA Inc.; 2014 [15 Sep 2014]. Available from: http://www.genscript.com/cgi-bin/ orf/browse.pl?species ⫽ 9606&type ⫽ locus&chromosome ⫽ 1&l ocus ⫽ 1p34&page ⫽ 1 17. Chromosome: 4 Map Location: 4q34: GenScript USA Inc.; 2014 [15 Sep 2014]. Available from: http://www.genscript.com/cgi-bin/ orf/browse.pl?species ⫽ 9606&type ⫽ locus&chromosome ⫽ 4&l ocus ⫽ 4q34 18. CASP3 caspase 3, apoptosis-related cysteine peptidase [Homo sapiens (human)]: HUGO gene nomenclature committee; 2014 [updated 11 Sep 2014]. Available from: http://www.ncbi.nlm.nih. gov/gene/836 19. Tiso N, Pallavicini A, Muraro T, et al. Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis. Biochem Biophys Res Commun 1996; 225:983–9 20. Choi Y, Ballow DJ, Xin Y, Rajkovic A. Lim homeobox gene, lhx8, is essential for mouse oocyte differentiation and survival. Biol Reprod 2008;79:442–9 21. Izawa M, Nguyen PH, Kim HH, Yeh J. Expression of the apoptosis-related genes, caspase-1, caspase-3, DNA fragmentation factor, and apoptotic protease activating factor-1, in human granulosa cells. Fertil Steril 1998;70:549–52 22. Matikainen T, Perez GI, Zheng TS, et al. Caspase-3 gene knockout defines cell lineage specificity for programmed cell death signaling in the ovary. Endocrinology 2001;142: 2468–80 23. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 2013;5:a008656 24. de Villiers TJ, Pines A, Panay N, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric 2013;16:316–37
3
