Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response
Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of...
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| Veröffentlicht in: | Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2024-03, Vol.31 (3), p.840-850 |
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| creator | Mehdizadeh, Anahita Soleimani, Mansoureh Amjadi, Fatemehsadat Sene, Azadeh Akbari Sheikhha, Mohammad Hassan Dehghani, Ali Ashourzadeh, Sareh Aali, Bibi Shahnaz Dabiri, Shahriar Zandieh, Zahra |
| description | Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between
BMP15
and
GDF9
variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of
BMP15
and
GDF9
were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of
BMP15
and
GDF9
genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32–4.11,
p
= 0.004).
The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response. |
| doi_str_mv | 10.1007/s43032-023-01370-1 |
| format | Article |
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BMP15
and
GDF9
variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of
BMP15
and
GDF9
were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of
BMP15
and
GDF9
genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32–4.11,
p
= 0.004).
The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response.</description><identifier>ISSN: 1933-7191</identifier><identifier>ISSN: 1933-7205</identifier><identifier>EISSN: 1933-7205</identifier><identifier>DOI: 10.1007/s43032-023-01370-1</identifier><identifier>PMID: 37848645</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Bone Morphogenetic Protein 15 - genetics ; Bone Morphogenetic Protein 15 - metabolism ; Embryology ; Female ; Follicular Fluid - metabolism ; Growth Differentiation Factor 9 - genetics ; Growth Differentiation Factor 9 - metabolism ; Humans ; Medicine ; Medicine & Public Health ; Obstetrics/Perinatology/Midwifery ; Oocytes - metabolism ; Ovary - metabolism ; Reproductive Genetics: Original Article ; Reproductive Medicine</subject><ispartof>Reproductive sciences (Thousand Oaks, Calif.), 2024-03, Vol.31 (3), p.840-850</ispartof><rights>The Author(s), under exclusive licence to Society for Reproductive Investigation 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c298t-c9d2bccf61a514922d9f4001834ed3efe671481112c439feeb797b29f0a46d243</cites><orcidid>0000-0002-7720-9465</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s43032-023-01370-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s43032-023-01370-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37848645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mehdizadeh, Anahita</creatorcontrib><creatorcontrib>Soleimani, Mansoureh</creatorcontrib><creatorcontrib>Amjadi, Fatemehsadat</creatorcontrib><creatorcontrib>Sene, Azadeh Akbari</creatorcontrib><creatorcontrib>Sheikhha, Mohammad Hassan</creatorcontrib><creatorcontrib>Dehghani, Ali</creatorcontrib><creatorcontrib>Ashourzadeh, Sareh</creatorcontrib><creatorcontrib>Aali, Bibi Shahnaz</creatorcontrib><creatorcontrib>Dabiri, Shahriar</creatorcontrib><creatorcontrib>Zandieh, Zahra</creatorcontrib><title>Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response</title><title>Reproductive sciences (Thousand Oaks, Calif.)</title><addtitle>Reprod. Sci</addtitle><addtitle>Reprod Sci</addtitle><description>Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between
BMP15
and
GDF9
variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of
BMP15
and
GDF9
were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of
BMP15
and
GDF9
genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32–4.11,
p
= 0.004).
The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response.</description><subject>Bone Morphogenetic Protein 15 - genetics</subject><subject>Bone Morphogenetic Protein 15 - metabolism</subject><subject>Embryology</subject><subject>Female</subject><subject>Follicular Fluid - metabolism</subject><subject>Growth Differentiation Factor 9 - genetics</subject><subject>Growth Differentiation Factor 9 - metabolism</subject><subject>Humans</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Obstetrics/Perinatology/Midwifery</subject><subject>Oocytes - metabolism</subject><subject>Ovary - metabolism</subject><subject>Reproductive Genetics: Original Article</subject><subject>Reproductive Medicine</subject><issn>1933-7191</issn><issn>1933-7205</issn><issn>1933-7205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMlOwzAQhi0EYim8AAfkI5eAx3Zq-8hakFgqBFwt15mgoNQOdlrB2xMocOQ0I_2LZj5C9oEdAWPqOEvBBC8YFwUDoVgBa2QbjBCF4qxc_93BwBbZyfmVsVIarjfJllBa6rEst8n0et61jXd9EwONNb2LS2zp6e0USupCRSfnl4Y-u9S40GfaBPoU8L1D32NFpzEmer_8FukD5i6GjLtko3Ztxr2fOSJPlxePZ1fFzf3k-uzkpvDc6L7wpuIz7-sxuBKGq3hlaskYaCGxEljjWIHUAMC9FKZGnCmjZtzUzMlxxaUYkcNVb5fi2wJzb-dN9ti2LmBcZMu10oqZstSDla-sPsWcE9a2S83cpQ8LzH6RtCuSdiBpv0laGEIHP_2L2Ryrv8gvusEgVoY8SOEFk32NixSGn_-r_QSNzHx9</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Mehdizadeh, Anahita</creator><creator>Soleimani, Mansoureh</creator><creator>Amjadi, Fatemehsadat</creator><creator>Sene, Azadeh Akbari</creator><creator>Sheikhha, Mohammad Hassan</creator><creator>Dehghani, Ali</creator><creator>Ashourzadeh, Sareh</creator><creator>Aali, Bibi Shahnaz</creator><creator>Dabiri, Shahriar</creator><creator>Zandieh, Zahra</creator><general>Springer International Publishing</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7720-9465</orcidid></search><sort><creationdate>20240301</creationdate><title>Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response</title><author>Mehdizadeh, Anahita ; Soleimani, Mansoureh ; Amjadi, Fatemehsadat ; Sene, Azadeh Akbari ; Sheikhha, Mohammad Hassan ; Dehghani, Ali ; Ashourzadeh, Sareh ; Aali, Bibi Shahnaz ; Dabiri, Shahriar ; Zandieh, Zahra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c298t-c9d2bccf61a514922d9f4001834ed3efe671481112c439feeb797b29f0a46d243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Bone Morphogenetic Protein 15 - genetics</topic><topic>Bone Morphogenetic Protein 15 - metabolism</topic><topic>Embryology</topic><topic>Female</topic><topic>Follicular Fluid - metabolism</topic><topic>Growth Differentiation Factor 9 - genetics</topic><topic>Growth Differentiation Factor 9 - metabolism</topic><topic>Humans</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Obstetrics/Perinatology/Midwifery</topic><topic>Oocytes - metabolism</topic><topic>Ovary - metabolism</topic><topic>Reproductive Genetics: Original Article</topic><topic>Reproductive Medicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mehdizadeh, Anahita</creatorcontrib><creatorcontrib>Soleimani, Mansoureh</creatorcontrib><creatorcontrib>Amjadi, Fatemehsadat</creatorcontrib><creatorcontrib>Sene, Azadeh Akbari</creatorcontrib><creatorcontrib>Sheikhha, Mohammad Hassan</creatorcontrib><creatorcontrib>Dehghani, Ali</creatorcontrib><creatorcontrib>Ashourzadeh, Sareh</creatorcontrib><creatorcontrib>Aali, Bibi Shahnaz</creatorcontrib><creatorcontrib>Dabiri, Shahriar</creatorcontrib><creatorcontrib>Zandieh, Zahra</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Reproductive sciences (Thousand Oaks, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mehdizadeh, Anahita</au><au>Soleimani, Mansoureh</au><au>Amjadi, Fatemehsadat</au><au>Sene, Azadeh Akbari</au><au>Sheikhha, Mohammad Hassan</au><au>Dehghani, Ali</au><au>Ashourzadeh, Sareh</au><au>Aali, Bibi Shahnaz</au><au>Dabiri, Shahriar</au><au>Zandieh, Zahra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response</atitle><jtitle>Reproductive sciences (Thousand Oaks, Calif.)</jtitle><stitle>Reprod. Sci</stitle><addtitle>Reprod Sci</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>31</volume><issue>3</issue><spage>840</spage><epage>850</epage><pages>840-850</pages><issn>1933-7191</issn><issn>1933-7205</issn><eissn>1933-7205</eissn><abstract>Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between
BMP15
and
GDF9
variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of
BMP15
and
GDF9
were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of
BMP15
and
GDF9
genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32–4.11,
p
= 0.004).
The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>37848645</pmid><doi>10.1007/s43032-023-01370-1</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7720-9465</orcidid></addata></record> |
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| source | MEDLINE; Springer journals |
| subjects | Bone Morphogenetic Protein 15 - genetics Bone Morphogenetic Protein 15 - metabolism Embryology Female Follicular Fluid - metabolism Growth Differentiation Factor 9 - genetics Growth Differentiation Factor 9 - metabolism Humans Medicine Medicine & Public Health Obstetrics/Perinatology/Midwifery Oocytes - metabolism Ovary - metabolism Reproductive Genetics: Original Article Reproductive Medicine |
| title | Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response |
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